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Sample records for pulmonary surfactant protein

  1. Biophysical inhibition of pulmonary surfactant function by polymeric nanoparticles: role of surfactant protein B and C.

    Science.gov (United States)

    Beck-Broichsitter, Moritz; Ruppert, Clemens; Schmehl, Thomas; Günther, Andreas; Seeger, Werner

    2014-11-01

    The current study investigated the mechanisms involved in the process of biophysical inhibition of pulmonary surfactant by polymeric nanoparticles (NP). The minimal surface tension of diverse synthetic surfactants was monitored in the presence of bare and surface-decorated (i.e. poloxamer 407) sub-100 nm poly(lactide) NP. Moreover, the influence of NP on surfactant composition (i.e. surfactant protein (SP) content) was studied. Dose-elevations of SP advanced the biophysical activity of the tested surfactant preparation. Surfactant-associated protein C supplemented phospholipid mixtures (PLM-C) were shown to be more susceptible to biophysical inactivation by bare NP than phospholipid mixture supplemented with surfactant protein B (PLM-B) and PLM-B/C. Surfactant function was hindered owing to a drastic depletion of the SP content upon contact with bare NP. By contrast, surface-modified NP were capable of circumventing unwanted surfactant inhibition. Surfactant constitution influences the extent of biophysical inhibition by polymeric NP. Steric shielding of the NP surface minimizes unwanted NP-surfactant interactions, which represents an option for the development of surfactant-compatible nanomedicines.

  2. Surfactant protein A and surfactant protein D variation in pulmonary disease

    DEFF Research Database (Denmark)

    Sørensen, Grith Lykke; Husby, Steffen; Holmskov, Uffe

    2007-01-01

    Surfactant proteins A (SP-A) and D (SP-D) have been implicated in pulmonary innate immunity. The proteins are host defense lectins, belonging to the collectin family which also includes mannan-binding lectin (MBL). SP-A and SP-D are pattern-recognition molecules with the lectin domains binding...... molecules present on immune cells leading to enhanced microbial clearance and modulation of inflammation. SP-A and SP-D also modulate the functions of cells of the adaptive immune system including dendritic cells and T cells. Studies on SP-A and SP-D polymorphisms and protein levels in bronchoalveolar...... preferentially to sugars on a broad spectrum of pathogen surfaces and thereby facilitating immune functions including viral neutralization, clearance of bacteria, fungi and apoptotic and necrotic cells, modulation of allergic reactions, and resolution of inflammation. SP-A and SP-D can interact with receptor...

  3. Pulmonary surfactant and lung transplantation

    NARCIS (Netherlands)

    Erasmus, Michiel Elardus

    1997-01-01

    Pulmonary surfactant lowers the surface tension at the air-water interface inside the alveolus. This is achieved by adsorption of surfactant phospholipids at the air-water interface, a process controlled by surfactant-associated proteins, such as SP-A. In this way, surfactant prevents collapse of th

  4. Production and characterisation of recombinant forms of human pulmonary surfactant protein C (SP-C)

    DEFF Research Database (Denmark)

    Lukovic, Dunja; Plasencia, Inés; Taberner, Francisco J

    2006-01-01

    Surfactant protein C (SP-C) is an essential component for the surface tension-lowering activity of the pulmonary surfactant system. It contains a valine-rich alpha helix that spans the lipid bilayer, and is one of the most hydrophobic proteins known so far. SP-C is also an essential component...... of various surfactant preparations of animal origin currently used to treat neonatal respiratory distress syndrome (NRDS) in preterm infants. The limited supply of this material and the risk of transmission of infectious agents and immunological reactions have prompted the development of synthetic SP...

  5. Surfactant protein D, a clinical biomarker for chronic obstructive pulmonary disease with excellent discriminant values

    DEFF Research Database (Denmark)

    Akiki, Zeina; Fakih, Dalia; Jounblat, Rania

    2016-01-01

    Biological markers can help to better identify a disease or refine its diagnosis. In the present study, the association between surfactant protein D (SP-D) and chronic obstructive pulmonary disease (COPD) was studied among subjects consulting for respiratory diseases or symptoms and was compared...

  6. Orphan G protein-coupled receptor GPR116 regulates pulmonary surfactant pool size.

    Science.gov (United States)

    Bridges, James P; Ludwig, Marie-Gabrielle; Mueller, Matthias; Kinzel, Bernd; Sato, Atsuyasu; Xu, Yan; Whitsett, Jeffrey A; Ikegami, Machiko

    2013-09-01

    Pulmonary surfactant levels within the alveoli are tightly regulated to maintain lung volumes and promote efficient gas exchange across the air/blood barrier. Quantitative and qualitative abnormalities in surfactant are associated with severe lung diseases in children and adults. Although the cellular and molecular mechanisms that control surfactant metabolism have been studied intensively, the critical molecular pathways that sense and regulate endogenous surfactant levels within the alveolus have not been identified and constitute a fundamental knowledge gap in the field. In this study, we demonstrate that expression of an orphan G protein-coupled receptor, GPR116, in the murine lung is developmentally regulated, reaching maximal levels 1 day after birth, and is highly expressed on the apical surface of alveolar type I and type II epithelial cells. To define the physiological role of GPR116 in vivo, mice with a targeted mutation of the Gpr116 locus, Gpr116(Δexon17), were generated. Gpr116(Δexon17) mice developed a profound accumulation of alveolar surfactant phospholipids at 4 weeks of age (12-fold) that was further increased at 20 weeks of age (30-fold). Surfactant accumulation in Gpr116(Δexon17) mice was associated with increased saturated phosphatidylcholine synthesis at 4 weeks and the presence of enlarged, lipid-laden macrophages, neutrophilia, and alveolar destruction at 20 weeks. mRNA microarray analyses indicated that P2RY2, a purinergic receptor known to mediate surfactant secretion, was induced in Gpr116(Δexon17) type II cells. Collectively, these data support the concept that GPR116 functions as a molecular sensor of alveolar surfactant lipid pool sizes by regulating surfactant secretion.

  7. Comprehensive characterisation of pulmonary and serum surfactant protein D in COPD

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    Erpenbeck Veit J

    2011-03-01

    Full Text Available Abstract Background Pulmonary surfactant protein D (SP-D is considered as a candidate biomarker for the functional integrity of the lung and for disease progression, which can be detected in serum. The origin of SP-D in serum and how serum concentrations are related to pulmonary concentrations under inflammatory conditions is still unclear. Methods In a cross-sectional study comprising non-smokers (n = 10, young - (n = 10, elderly smokers (n = 20, and smokers with COPD (n = 20 we simultaneously analysed pulmonary and serum SP-D levels with regard to pulmonary function, exercise, repeatability and its quaternary structure by native gel electrophoresis. Statistical comparisons were conducted by ANOVA and post-hoc testing for multiple comparisons; repeatability was assessed by Bland-Altman analysis. Results In COPD, median (IQR pulmonary SP-D levels were lower (129(68 ng/ml compared to smokers (young: 299(190, elderly: 296(158 ng/ml; p Conclusions Pulmonary and serum SP-D levels are stable markers influenced by smoking and related to airflow obstruction and disease state. Smaller subunits of pulmonary SP-D and the rapid increase of serum SP-D levels in COPD due to exercise support the translocation hypothesis and its use as a COPD biomarker. Trial registration no interventional trial

  8. Interaction of the N-terminal segment of pulmonary surfactant protein SP-C with interfacial phospholipid films

    DEFF Research Database (Denmark)

    Plasencia, Inés; Keough, Kevin M W; Perez-Gil, Jesus

    2005-01-01

    Pulmonary surfactant protein SP-C is a 35-residue polypeptide composed of a hydrophobic transmembrane alpha-helix and a polycationic, palmitoylated-cysteine containing N-terminal segment. This segment is likely the only structural motif the protein projects out of the bilayer in which SP-C is ins......Pulmonary surfactant protein SP-C is a 35-residue polypeptide composed of a hydrophobic transmembrane alpha-helix and a polycationic, palmitoylated-cysteine containing N-terminal segment. This segment is likely the only structural motif the protein projects out of the bilayer in which SP...

  9. Selective labeling of pulmonary surfactant protein SP-C in organic solution

    DEFF Research Database (Denmark)

    Plasencia, I; Cruz, A; López-Lacomba, J L

    2001-01-01

    Pulmonary surfactant protein SP-C has been isolated from porcine lungs and treated with dansyl isothiocyanate in chloroform:methanol 2:1 (v/v) solutions,under conditions optimized to introduce a single dansyl group covalently attached to the N-terminalamine group of the protein without loss of its...... native thioesther-linked palmitic chains. The resulting derivative Dans-SP-C conserves the secondary structure of native SP-C as well as the ability to promote interfacial adsorption of DPPC suspensions and to affect the thermotropic behavior of DPPC bilayers. This derivative can be used to characterize...... lipid-protein and protein-protein interactions of a native-like SP-C in lipid/protein complexes. Udgivelsesdato: 2001-Sep-1...

  10. Surfactant protein-B 121ins2 heterozygosity, reduced pulmonary function, and chronic obstructive pulmonary disease in smokers

    DEFF Research Database (Denmark)

    Bækvad-Hansen, Marie; Dahl, Morten; Tybjaerg-Hansen, Anne

    2010-01-01

    Hereditary surfactant protein-B deficiency is an autosomal recessive disorder that causes fatal respiratory distress syndrome in newborns. Seventy percent of the cases of hereditary surfactant protein-B deficiency are caused by homozygosity for the 121ins2 mutation in the surfactant protein-B gene...

  11. Immunohistochemical investigation of pulmonary surfactant-associated protein A in fire victims.

    Science.gov (United States)

    Zhu, B L; Ishida, K; Oritani, S; Quan, L; Taniguchi, M; Li, D R; Fujita, M Q; Maeda, H

    2001-03-01

    To evaluate the forensic pathological significance of the immunohistochemical distribution of pulmonary surfactant-associated protein A (SP-A) in determining the cause of death in fires, 57 fire victims were examined by scoring the staining intensity. The highest SP-A score with dense granular deposits (aggregates) in the intra-alveolar space was frequently observed in cases with a lower blood carboxyhemoglobin (COHb) level (fires. High SP-A scores showed a relation to the serum level and in part related to the bloody exudate in the lower airway. These observations suggested that the increase in SP-A in fire victims may be mainly related to pulmonary alveolar injury due to the inhalation of hot air and/or irritant gases rather than hypoxia.

  12. Surfactant Protein-B 121ins2 Heterozygosity, Reduced Pulmonary Function and COPD in Smokers

    DEFF Research Database (Denmark)

    Bækvad-Hansen, Marie; Dahl, Morten; Tybjærg-Hansen, Anne

    2010-01-01

    RATIONALE: Hereditary surfactant protein-B deficiency is an autosomal recessive disorder that causes fatal respiratory distress syndrome in newborns. Seventy percent of the cases of hereditary surfactant protein-B deficiency are caused by homozygosity for the 121ins2 mutation in the surfactant...

  13. [Surfactant protein and thyroid transcription factor 1 in pleuro-pulmonary neoplasia. Immunohistochemical study].

    Science.gov (United States)

    Dessy, E; Falleni, M; Del Curto, B; Braidotti, P; Pietra, G G

    2000-12-01

    Aim of this work was to investigate the ability of the antibodies against Surfactant proteins (SP) and Thyroid transcription factor 1 (TTF-1) to distinguish primary neoplasms of the lung from metastatic carcinomas to the lung and pleural mesotheliomas. We evaluated the immunohistochemical expression of the antibodies anti SP-A, SP-B, pro SP-C, SP-D, and TTF-1 in a series of 56 primary lung carcinomas, 9 metastatic carcinomas to the lung, 5 pleural mesotheliomas and 8 non-pulmonary carcinomas. Among primary lung neoplasms, only adenocarcinomas immunostained for all SP (specificity = 1; total sensitivity = 0.52). TTF-1 had an excellent specificity (= 1), but a weak sensitivity (= 0.34) in recognizing primary lung carcinomas. TTF-1 was present in lung adenocarcinomas which were negative for SPs; however it failed to distinguish the subtypes. Pleural mesotheliomas, pulmonary metastases and non-pulmonary carcinomas were not immunoreactive for SP-A, SP-B, SP-D, and TTF-1. Pro SP-C was positive also in the adenocarcinomas of the large bowel and in their pulmonary and nodal metastases. These results demonstrate that the combined use of antibodies anti SP-A, SP-B and TTF-1 is the best association in distinguishing primary lung carcinomas from metastatic carcinomas to the lung and pleural mesotheliomas.

  14. C-reactive protein increases membrane fluidity and distorts lipid lateral organization of pulmonary surfactant. Protective role of surfactant protein A

    DEFF Research Database (Denmark)

    Saenz, Alejandra; Lopez-Sanchez, Almudena; Mojica-Lazaro, Jonas

    2010-01-01

    The purpose of this study was to investigate how surfactant membranes can be perturbed by C-reactive protein (CRP) and whether surfactant protein A (SP-A) might overcome CRP-induced surfactant membrane alterations. The effect of CRP on surfactant surface adsorption was evaluated in vivo after int...

  15. Influence of ulinastatin on pulmonary surfactant protein, anti-inflammatory and pro-inflammatory mediator in patients with severe pneumonia

    Institute of Scientific and Technical Information of China (English)

    Li Wang; Rui Kang; Jia-Li Xie; Ya-Ni Xue

    2016-01-01

    Objective:To observe the influence of ulinastatin on pulmonary surfactant protein and anti-inflammatory and pro-inflammatory mediator in patients with severe pneumonia. Methods:A total of 54 patients with severe pneumonia treated in our hospital from April 2014 to May 2015 were selected as the study object, and they were randomly divided into control group (conventional treatment of severe pneumonia group) and observation group (conventional treatment and ulinastatin group), with 27 cases in each group. Then the serum levels of pulmonary surfactant protein,anti-inflammatory and pro-inflammatory mediators in two groups before and after treatment at 1 day, 3 day and 5 day were compared. Results:The serum level of pulmonary surfactant protein, anti-inflammatory and pro-inflammatory mediators in two groups before treatment had no significant differences, all P>0.05, and those serum indexes in observation group after treatment at 1 day, 3 day and 5 day were all significantly better than those of the control group, all P<0.05. Conclusions:The ulinastatin can effectively improve the pulmonary surfactant protein, anti-inflammatory and pro-inflammatory mediators in patients with severe pneumonia, and its improvement role for various of severe pneumonia are obvious.

  16. Surfactant protein B polymorphisms, pulmonary function and COPD in 10,231 individuals

    DEFF Research Database (Denmark)

    Bækvad-Hansen, M; Nordestgaard, B G; Dahl, Morten

    2011-01-01

    The surfactant protein (SP)-B gene may influence chronic obstructive pulmonary disease (COPD) and, thus, personalised medicine. We tested whether functional polymorphisms in SP-B (rs1130866 (1580T>C), rs2077079 (-18A>C) and rs3024791 (-384G>A)) associate with reduced lung function and risk of COPD...... in the general population. We genotyped 10,231 individuals from the general adult Danish population, and recorded spirometry and hospital admissions due to COPD. Because we previously found an association between the rare SP-B 121ins2 mutation and COPD among smokers, we stratified the analyses for smoking status....... None of the individual SP-B genotypes or genotype combinations were associated with reduced forced expiratory volume in 1 s (FEV1) % predicted, forced vital capacity (FVC) % pred and FEV1/FVC overall or among smokers (p = 0.25-0.99). The odds ratio for spirometrically defined COPD did not differ from 1...

  17. Study on the influence of puerarin injection for the pulmonary surfactant protein and inflammatory mediators of children with severe pneumonia

    Institute of Scientific and Technical Information of China (English)

    Lv-Wei Zhang

    2015-01-01

    Objective: To study and observe the influence situation of puerarin injection for the pulmonary surfactant protein and inflammatory mediators of children with severe pneumonia. Methods: 60 children with severe pneumonia in our hospital from February 2013 to January 2015 were selected as study object,and they were randomly divided into control group (routine treatment group) 30 cases and observation group (routine treatment and puerarin injection group) 30 cases, then the serum pulmonary surfactant protein and inflammatory mediators of two groups before the treatment and at different time after the treatment were respectively detected and compared. Results: The serum ulmonary surfactant protein and inflammatory mediators of observation group at third,fifth and tenth day after the treatment were all obviously lower than those of control group, all P<0.05, the comparison indexes after the treatment all had significant differences. Conclusions: The influence of puerarin injection for the pulmonary surfactant protein and inflammatory mediators of children with severe pneumonia are great, and it can effectively improve the disease state of children with severe pneumonia.

  18. Serum Levels of Surfactant Proteins in Patients with Combined Pulmonary Fibrosis and Emphysema (CPFE.

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    Andriana I Papaioannou

    Full Text Available Emphysema and idiopathic pulmonary fibrosis (IPF present either per se or coexist in combined pulmonary fibrosis and emphysema (CPFE. Serum surfactant proteins (SPs A, B, C and D levels may reflect lung damage. We evaluated serum SP levels in healthy controls, emphysema, IPF, and CPFE patients and their associations to disease severity and survival.122 consecutive patients (31 emphysema, 62 IPF, and 29 CPFE and 25 healthy controls underwent PFTs, ABG-measurements, 6MWT and chest HRCT. Serum levels of SPs were measured. Patients were followed-up for 1-year.SP-A and SP-D levels differed between groups (p = 0.006 and p<0.001 respectively. In post-hoc analysis, SP-A levels differed only between controls and CPFE (p<0.05 and CPFE and emphysema (p<0.05. SP-D differed between controls and IPF or CPFE (p<0.001 for both comparisons. In IPF SP-B correlated to pulmonary function while SP-A, correlated to the Composite Physiological Index (CPI. Controls current smokers had higher SP-A and SP-D levels compared to non-smokers (p = 0.026 and p = 0.023 respectively. SP-D levels were higher in CPFE patients with extended emphysema (p = 0.042. In patients with IPF, SP-B levels at the upper quartile of its range (≥26 ng/mL presented a weak association with reduced survival (p = 0.05.In conclusion, serum SP-A and SP-D levels were higher where fibrosis exists or coexists and related to disease severity, suggesting that serum SPs relate to alveolar damage in fibrotic lungs and may reflect either local overproduction or overleakage. The weak association between high levels of SP-B and survival needs further validation in clinical trials.

  19. The elevation of serum napsin A in idiopathic pulmonary fibrosis, compared with KL-6, surfactant protein-A and surfactant protein-D

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    Samukawa Takuya

    2012-09-01

    Full Text Available Abstract Background Napsin A, an aspartic protease, is mainly expressed in alveolar type-II cells and renal proximal tubules and is a putative immunohistochemical marker for pulmonary adenocarcinomas. This study sought to determine whether napsin A could be measured in the serum to evaluate its relationship to idiopathic pulmonary fibrosis (IPF and determine whether renal dysfunction might affect serum napsin A levels. Methods Serum levels of napsin A were measured in 20 patients with IPF, 34 patients with lung primary adenocarcinoma, 12 patients with kidney diseases, and 20 healthy volunteers. Surfactant protein (SP-A, SP-D, and Krebs von den Lungen-6 (KL-6 levels in serum and pulmonary function tests were also evaluated in IPF patients. Results Circulating levels of napsin A were increased in patients with IPF, as compared with healthy controls, and they correlated with the severity of disease. Moreover, the serum napsin A levels were not elevated in patients with pulmonary adenocarcinoma or renal dysfunction. The distinguishing point between IPF and the controls was that the area under the receiver operating characteristic curve (ROC of napsin A was larger than that of KL-6, SP-A, or SP-D. Conclusion These findings suggest that serum napsin A may be a candidate biomarker for IPF.

  20. Surfactant protein A2 mutations associated with pulmonary fibrosis lead to protein instability and endoplasmic reticulum stress.

    Science.gov (United States)

    Maitra, Meenakshi; Wang, Yongyu; Gerard, Robert D; Mendelson, Carole R; Garcia, Christine Kim

    2010-07-16

    Rare heterozygous mutations in the gene encoding surfactant protein A2 (SP-A2, SFTPA2) are associated with adult-onset pulmonary fibrosis and adenocarcinoma of the lung. We have previously shown that two recombinant SP-A2 mutant proteins (G231V and F198S) remain within the endoplasmic reticulum (ER) of A549 cells and are not secreted into the culture medium. The pathogenic mechanism of the mutant proteins is unknown. Here we analyze all common and rare variants of the surfactant protein A2, SP-A2, in both A549 cells and in primary type II alveolar epithelial cells. We show that, in contrast with all other SP-A2 variants, the mutant proteins are not secreted into the medium with wild-type SP-A isoforms, form fewer intracellular dimer and trimer oligomers, are partially insoluble in 0.5% Nonidet P-40 lysates of transfected A549 cells, and demonstrate greater protein instability in chymotrypsin proteolytic digestions. Both the G231V and F198S mutant SP-A2 proteins are destroyed via the ER-association degradation pathway. Expression of the mutant proteins increases the transcription of a BiP-reporter construct, expression of BiP protein, and production of an ER stress-induced XBP-1 spliced product. Human bronchoalveolar wash samples from individuals who are heterozygous for the G231V mutation have similar levels of total SP-A as normal family members, which suggests that the mechanism of disease does not involve an overt lack of secreted SP-A but instead involves an increase in ER stress of resident type II alveolar epithelial cells.

  1. Quantitation of pulmonary surfactant protein SP-B in the absence or presence of phospholipids by enzyme-linked immunosorbent assay

    DEFF Research Database (Denmark)

    Oviedo, J M; Valiño, F; Plasencia, I

    2001-01-01

    We have developed an enzyme-linked immunosorbent assay (ELISA) that uses polyclonal or monoclonal anti-surfactant protein SP-B antibodies to quantitate purified SP-B in chloroform/methanol and in chloroform/methanol extracts of whole pulmonary surfactant at nanogram levels. This method has been...

  2. Depth profiles of pulmonary surfactant protein B in phosphatidylcholine bilayers, studied by fluorescence and electron spin resonance spectroscopy

    DEFF Research Database (Denmark)

    Cruz, A; Casals, C; Plasencia, I

    1998-01-01

    . These differences in the extent of insertion lead to qualitative and quantitative differences in the effect of the protein on the mobility of the phospholipid acyl chains, as studied by spin-label electron spin resonance (ESR) spectroscopy, and could represent different functional stages in the surfactant cycle......Pulmonary surfactant-associated protein B (SP-B) has been isolated from porcine lungs and reconstituted in bilayers of dipalmitoylphosphatidylcholine (DPPC) or egg yolk phosphatidylcholine (PC) to characterize the extent of insertion of the protein into phospholipid bilayers. The parameters...... for the interaction of SP-B with DPPC or PC using different reconstitution protocols have been estimated from the changes induced in the fluorescence emission spectrum of the single protein tryptophan. All the different reconstituted SP-B-phospholipid preparations studied had similar Kd values for the binding...

  3. Cis-acting sequences from a human surfactant protein gene confer pulmonary-specific gene expression in transgenic mice

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    Korfhagen, T.R.; Glasser, S.W.; Wert, S.E.; Bruno, M.D.; Daugherty, C.C.; McNeish, J.D.; Stock, J.L.; Potter, S.S.; Whitsett, J.A. (Cincinnati College of Medicine, OH (USA))

    1990-08-01

    Pulmonary surfactant is produced in late gestation by developing type II epithelial cells lining the alveolar epithelium of the lung. Lack of surfactant at birth is associated with respiratory distress syndrome in premature infants. Surfactant protein C (SP-C) is a highly hydrophobic peptide isolated from pulmonary tissue that enhances the biophysical activity of surfactant phospholipids. Like surfactant phospholipid, SP-C is produced by epithelial cells in the distal respiratory epithelium, and its expression increases during the latter part of gestation. A chimeric gene containing 3.6 kilobases of the promoter and 5{prime}-flanking sequences of the human SP-C gene was used to express diphtheria toxin A. The SP-C-diphtheria toxin A fusion gene was injected into fertilized mouse eggs to produce transgenic mice. Affected mice developed respiratory failure in the immediate postnatal period. Morphologic analysis of lungs from affected pups showed variable but severe cellular injury confined to pulmonary tissues. Ultrastructural changes consistent with cell death and injury were prominent in the distal respiratory epithelium. Proximal components of the tracheobronchial tree were not severely affected. Transgenic animals were of normal size at birth, and structural abnormalities were not detected in nonpulmonary tissues. Lung-specific diphtheria toxin A expression controlled by the human SP-C gene injured type II epithelial cells and caused extensive necrosis of the distal respiratory epithelium. The absence of type I epithelial cells in the most severely affected transgenic animals supports the concept that developing type II cells serve as precursors to type I epithelial cells.

  4. Alterations in pulmonary surfactant protein a metabolism and its diagnostic value in onset of radiation pneumonitis

    Energy Technology Data Exchange (ETDEWEB)

    Imai, Yoshinari; Takahashi, Hiroki [Sapporo Medical Univ. (Japan)

    1999-12-01

    Radiation pneumonitis (RP) is a serious disorder caused by radiation therapy, for the detection of which there exists no simple and sensitive clinical examination. In this study, we examined whether the measurement of serum pulmonary surfactant protein A (SP-A) levels could be effective for detecting the onset of RP. Of the 18 patients included in the study, 9 suffered RP complication after radiation therapy. Serum SP-A levels in patients with RP (64.1{+-}6.5 ng/ml) were 1.82 times as high as those of pre-radiation (36.2{+-}4.0 ng/ml). The difference between them was significant (p=0.0003), while the SP-A value in patients without RP after radiation therapy was almost the same as the pre-radiation level. To study the mechanisms of these elevations, we developed a model of whole lung irradiation (20 Gy) in adult rats. Prior to alveolitis, which was a histological change seen at day 28, levels of SP-A in lung tissue homogenates and bronchoalveolar lavage fluid had become elevated by day 21. Serum SP-A levels in the irradiated rats were significantly elevated by day 21, peaking at day 35, and then declined. Hydroxyproline contents in lung tissues were elevated by day 42 and remained so through day 56. Therefore, the increase in serum SP-A level may be reflected by alveolitis but not fibrosis. In conclusion, determination of serum SP-A could be helpful in detecting the onset of RP. (author)

  5. Pseudomonas aeruginosa elastase provides an escape from phagocytosis by degrading the pulmonary surfactant protein-A.

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    Zhizhou Kuang

    Full Text Available Pseudomonas aeruginosa is an opportunistic pathogen that causes both acute pneumonitis in immunocompromised patients and chronic lung infections in individuals with cystic fibrosis and other bronchiectasis. Over 75% of clinical isolates of P. aeruginosa secrete elastase B (LasB, an elastolytic metalloproteinase that is encoded by the lasB gene. Previously, in vitro studies have demonstrated that LasB degrades a number of components in both the innate and adaptive immune systems. These include surfactant proteins, antibacterial peptides, cytokines, chemokines and immunoglobulins. However, the contribution of LasB to lung infection by P. aeruginosa and to inactivation of pulmonary innate immunity in vivo needs more clarification. In this study, we examined the mechanisms underlying enhanced clearance of the ΔlasB mutant in mouse lungs. The ΔlasB mutant was attenuated in virulence when compared to the wild-type strain PAO1 during lung infection in SP-A+/+ mice. However, the ΔlasB mutant was as virulent as PAO1 in the lungs of SP-A⁻/⁻ mice. Detailed analysis showed that the ΔlasB mutant was more susceptible to SP-A-mediated opsonization but not membrane permeabilization. In vitro and in vivo phagocytosis experiments revealed that SP-A augmented the phagocytosis of ΔlasB mutant bacteria more efficiently than the isogenic wild-type PAO1. The ΔlasB mutant was found to have a severely reduced ability to degrade SP-A, consequently making it unable to evade opsonization by the collectin during phagocytosis. These results suggest that P. aeruginosa LasB protects against SP-A-mediated opsonization by degrading the collectin.

  6. [Pulmonary surfactant homeostasis associated genetic abnormalities and lung diseases].

    Science.gov (United States)

    Jiang, Xiaojing; Sun, Xiuzhu; Du, Weihua; Hao, Haisheng; Zhao, Xueming; Wang, Dong; Zhu, Huabin; Liu, Yan

    2016-08-01

    Pulmonary surfactant (PS) is synthesized and secreted by alveolar epithelial type II (AEII) cells, which is a complex compound formed by proteins and lipids. Surfactant participates in a range of physiological processes such as reducing the surface tension, keeping the balance of alveolar fluid, maintaining normal alveolar morphology and conducting host defense. Genetic disorders of the surfactant homeostasis genes may result in lack of surfactant or cytotoxicity, and lead to multiple lung diseases in neonates, children and adults, including neonatal respiratory distress syndrome, interstitial pneumonia, pulmonary alveolar proteinosis, and pulmonary fibrosis. This paper has provided a review for the functions and processes of pulmonary surfactant metabolism, as well as the connection between disorders of surfactant homeostasis genes and lung diseases.

  7. Surfactant protein D, Club cell protein 16, Pulmonary and activation-regulated chemokine, C-reactive protein, and Fibrinogen biomarker variation in chronic obstructive lung disease

    DEFF Research Database (Denmark)

    Johansson, Sofie Lock; Vestbo, J.; Sorensen, G. L.

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a multifaceted condition that cannot be fully described by the severity of airway obstruction. The limitations of spirometry and clinical history have prompted researchers to investigate a multitude of surrogate biomarkers of disease for the assessm......Chronic obstructive pulmonary disease (COPD) is a multifaceted condition that cannot be fully described by the severity of airway obstruction. The limitations of spirometry and clinical history have prompted researchers to investigate a multitude of surrogate biomarkers of disease...... for the assessment of patients, prediction of risk, and guidance of treatment. The aim of this review is to provide a comprehensive summary of observations for a selection of recently investigated pulmonary inflammatory biomarkers (Surfactant protein D (SP-D), Club cell protein 16 (CC-16), and Pulmonary...... and activation-regulated chemokine (PARC/CCL-18)) and systemic inflammatory biomarkers (C-reactive protein (CRP) and fibrinogen) with COPD. The relevance of these biomarkers for COPD is discussed in terms of their biological plausibility, their independent association to disease and hard clinical outcomes...

  8. Coccidioides posadasii infection alters the expression of pulmonary surfactant proteins (SP-A and SP-D

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    Magee D Mitchell

    2004-12-01

    Full Text Available Abstract Background Coccidioidomycosis or Valley Fever is caused by Coccidioides in Southwest US and Central America. Primary pulmonary infection is initiated by inhalation of air-borne arthroconidia. Since, lung is the first organ that encounters arthroconidia, different components of the pulmonary innate immune system may be involved in the regulation of host defense. Pulmonary surfactant proteins (SP-A and SP-D have been recognized to play an important role in binding and phagocytosis of various microorganisms, but their roles in Coccidioides infection are not known. Methods In this study, we studied the changes in amounts of pulmonary SP-A, SP-D and phospholipid in murine model of Coccidioides posadasii infection, and binding of SP-A and SP-D to Coccidioidal antigens. Mice were challenged intranasally with a lethal dose of C. posadasii (n = 30 arthroconidia and bronchoalveolar lavage fluid (BALF samples were collected on day 10, post infection. In another group of animals, mice were immunized with protective formalin killed spherule (FKS vaccine prior to infection. The concentrations of BALF SP-A, SP-D, total phospholipid were measured using enzyme linked immunosorbent assay and biochemical assays. Results We found that in lavage fluid samples of C. posadasii infected mice, the concentrations of total phospholipid, SP-A and SP-D were 17 % (SEM 3.5, p C. posadasii protected mice after immunization with FKS vaccine. Also, we found that both SP-A and SP-D bind to Coccidiodal antigens. Conclusion Our results suggest that the C. posadasii infection perturbs the pulmonary SP-A, SP-D, and phospholipids, potentially enabling the disease progression and promoting fungal dissemination.

  9. Chronic obstructive pulmonary disease and inhaled steroids alter surfactant protein D (SP-D levels: a cross-sectional study

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    Beers Michael F

    2008-01-01

    Full Text Available Abstract Background Surfactant protein D (SP-D, an innate immune molecule, plays an important protective role during airway inflammation. Deficiency of this molecule induces emphysematous changes in murine lungs, but its significance in human COPD remains unclear. Methods We collected bronchoalveolar lavage fluid from 20 subjects with varying degrees of COPD (8 former smokers and 12 current smokers and 15 asymptomatic healthy control subjects (5 never smokers, 3 remote former smokers, and 7 current smokers. All subjects underwent a complete medical history and pulmonary function testing. SP-D was measured by Enzyme-Linked ImmunoSorbent Assay. Statistical analysis was performed using nonparametric methods and multivariable linear regression for control of confounding. The effect of corticosteroid treatment on SP-D synthesis was studied in vitro using an established model of isolated type II alveolar epithelial cell culture. Results Among former smokers, those with COPD had significantly lower SP-D levels than healthy subjects (median 502 and 1067 ng/mL, respectively, p = 0.01. In a multivariable linear regression model controlling for age, sex, race, and pack-years of tobacco, COPD was independently associated with lower SP-D levels (model coefficient -539, p = 0.04 and inhaled corticosteroid use was independently associated with higher SP-D levels (398, p = 0.046. To support the hypothesis that corticosteroids increase SP-D production we used type II alveolar epithelial cells isolated from adult rat lungs. These cells responded to dexamethasone treatment by a significant increase of SP-D mRNA (p = 0.041 and protein (p = 0.037 production after 4 days of culture. Conclusion Among former smokers, COPD is associated with lower levels of SP-D and inhaled corticosteroid use is associated with higher levels of SP-D in the lung. Dexamethasone induced SP-D mRNA and protein expression in isolated epithelial cells in vitro. Given the importance of this

  10. Ultrastructural study of nuclear inclusions immunohistochemically positive for surfactant protein A in pulmonary adenocarcinoma with special reference to their morphogenesis.

    Science.gov (United States)

    Lu, Shu-Hui; Ohtsuki, Yuji; Nonami, Yoshiki; Sasaguri, Shiro; Fujita, Jiro; Uomoto, Masashi; Tao, Fu-Shan; Kobayashi, Makoto; Furihata, Mutsuo

    2006-12-01

    To investigate the fine-structural nature of nuclear inclusions immunopositive for surfactant protein A (SP-A) antibody staining, a detailed ultrastructural study was performed, as well as immunohistochemical examination of pulmonary adenocarcinomas. Surgically resected tumor specimens from 31 patients were examined by immunohistochemistry focused on reactivity to SP-A and thyroid transcription factor 1 (TTF-1) antibodies. Only cases with >5% positive nuclear inclusions in cancer cells were considered positive, some of which were examined by electron microscopy. Immunohistochemically, 6 of 31 cases were doubly positive for SP-A and TTF-1 antibodies. On electron microscopy, SP-A-positive nuclei contained diffuse or globular fine granular substance as inclusions. Both types of globular and diffuse inclusions were sometimes connected to the inner nuclear membrane, in association with fragmented or stacked membranous structures. The findings of this study suggested that nuclear inclusions positive for SP-A antibody staining in adenocarcinomas of the lung were derived from accumulated content in the perinuclear cistern resembling pseudoinclusion processes and composed of proteins antigenically cross-reactive with SP-A.

  11. Protective Effect of Surfactant Protein D in Pulmonary Vaccinia Virus Infection: Implication of A27 Viral Protein

    Directory of Open Access Journals (Sweden)

    Julien Perino

    2013-03-01

    Full Text Available Vaccinia virus (VACV was used as a surrogate of variola virus (VARV (genus Orthopoxvirus, the causative agent of smallpox, to study Orthopoxvirus infection. VARV is principally transmitted between humans by aerosol droplets. Once inhaled, VARV first infects the respiratory tract where it could encounter surfactant components, such as soluble pattern recognition receptors. Surfactant protein D (SP-D, constitutively present in the lining fluids of the respiratory tract, plays important roles in innate host defense against virus infection. We investigated the role of SP-D in VACV infection and studied the A27 viral protein involvement in the interaction with SP-D. Interaction between SP-D and VACV caused viral inhibition in a lung cell model. Interaction of SP-D with VACV was mediated by the A27 viral protein. Binding required Ca2+ and interactions were blocked in the presence of excess of SP-D saccharide ligands. A27, which lacks glycosylation, directly interacted with SP-D. The interaction between SP-D and the viral particle was also observed using electron microscopy. Infection of mice lacking SP-D (SP-D-/- resulted in increased mortality compared to SP-D+/+ mice. Altogether, our data show that SP-D participates in host defense against the vaccinia virus infection and that the interaction occurs with the viral surface protein A27.

  12. Surfactant apoprotein in nonmalignant pulmonary disorders.

    Science.gov (United States)

    Singh, G.; Katyal, S. L.

    1980-01-01

    Formalin-fixed, paraffin-embedded lungs exhibiting a variety of nonmalignant disorders were studied by immunoperoxidase staining using antibodies specific for surfactant apoprotein, IgG, IgM, IgA, albumin, fibrinogen, and lysozyme. Normal Type II pneumocytes showed staining for surfactant apoprotein in the perinuclear region only. The extent and intensity of staining for apoprotein was markedly increased in reactive Type II pneumocytes. This increase appeared to be a nonspecific reaction to lung injury. The intra-alveolar material in pulmonary alveolar proteinosis stained intensely for surfactant apoprotein, indicating that the accumulated proteinaceous material contained pulmonary surfactant. Type II pneumocytes in pulmonary alveolar proteinosis exhibited hyperplasia as well as hypertrophy. The few macrophages in lung affected by pulmonary alveolar proteinosis stained intensely for lysozyme. The excessive intraalveolar accumulation of proteinaceous material in pulmonary alveolar proteinosis may be the result of both an over-production as well as a deficient removal of pulmonary surfactant. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 p[57]-a PMID:7004201

  13. Barrier or carrier? Pulmonary surfactant and drug delivery.

    Science.gov (United States)

    Hidalgo, Alberto; Cruz, Antonio; Pérez-Gil, Jesús

    2015-09-01

    To consider the lung as a target for drug delivery and to optimise strategies directed at the pulmonary route, it is essential to consider the role of pulmonary surfactant, a thin lipid-protein film lining the respiratory surface of mammalian lungs. Membrane-based surfactant multilayers are essential for reducing the surface tension at the respiratory air-liquid interface to minimise the work of breathing. Different components of surfactant are also responsible for facilitating the removal of potentially pathological entities such as microorganisms, allergens or environmental pollutants and particles. Upon inhalation, drugs or nanoparticles first contact the surfactant layer, and these interactions critically affect their lifetime and fate in the airways. This review summarises the current knowledge on the possible role and effects of the pulmonary surfactant system in drug delivery strategies. It also summarises the evidence that suggests that pulmonary surfactant is far from being an insuperable barrier and could be used as an efficient shuttle for delivering hydrophobic and hydrophilic compounds deep into the lung and the organism.

  14. Pulmonary surfactant protein A inhibits the lipid peroxidation stimulated by linoleic acid hydroperoxide of rat lung mitochondria and microsomes.

    Science.gov (United States)

    Terrasa, Ana M; Guajardo, Margarita H; de Armas Sanabria, Elizabeth; Catalá, Angel

    2005-07-15

    Reactive oxygen species play an important role in several acute lung injuries. The lung tissue contains polyunsaturated fatty acids (PUFAs) that are substrates of lipid peroxidation that may lead to loss of the functional integrity of the cell membranes. In this study, we compare the in vitro protective effect of pulmonary surfactant protein A (SP-A), purified from porcine surfactant, against ascorbate-Fe(2+) lipid peroxidation stimulated by linoleic acid hydroperoxide (LHP) of the mitochondria and microsomes isolated from rat lung; deprived organelles of ascorbate and LHP were utilized as control. The process was measured simultaneously by chemiluminescence as well as by PUFA degradation of the total lipids isolated from these organelles. The addition of LHP to rat lung mitochondria or microsomes produces a marked increase in light emission; the highest value of activation was produced in microsomes (total chemiluminescence: 20.015+/-1.735 x 10(5) cpm). The inhibition of lipid peroxidation (decrease of chemiluminescence) was observed with the addition of increasing amounts (2.5 to 5.0 microg) of SP-A in rat lung mitochondria and 2.5 to 7.5 microg of SP-A in rat lung microsomes. The inhibitory effect reaches the highest values in the mitochondria, thus, 5.0 microg of SP-A produces a 100% inhibition in this membranes whereas 7.5 microg of SP-A produces a 51.25+/-3.48% inhibition in microsomes. The major difference in the fatty acid composition of total lipids isolated from native and peroxidized membranes was found in the arachidonic acid content; this decreased from 9.68+/-1.60% in the native group to 5.72+/-1.64% in peroxidized mitochondria and from 7.39+/-1.14% to 3.21+/-0.77% in microsomes. These changes were less pronounced in SP-A treated membranes; as an example, in the presence of 5.0 microg of SP-A, we observed a total protection of 20:4 n-6 (9.41+/-3.29%) in mitochondria, whereas 7.5 microg of SP-A produced a 65% protection in microsomes (5

  15. Interfacial behavior of pulmonary surfactant preparations containing egg yolk lecithin.

    Science.gov (United States)

    Nakahara, Hiromichi; Shibata, Osamu

    2014-01-01

    Mammalian lungs are covered with lipid-protein complexes or pulmonary surfactants. In this work, which aimed towards the less expensive production of artificial pulmonary surfactants, we produced surfactants composed of egg yolk lecithin (eggPC), palmitic acid, and hexadecanol (= 0.30/0.35/0.35, mol/mol/mol ) containing different amounts of Hel 13-5 (NH2-KLLKLLLKLWLKLLKLLL-COOH) as a substitute for the proteins in native pulmonary surfactants. Surface pressure (π)-molecular area (A) and surface potential (DV)-A isotherms of the mixtures were measured via the Wilhelmy and ionizing (241)Am electrode methods, respectively. The interactions between the lipid components and Hel 13-5 led to variations in the surface pressure caused by the expulsion of fluid components from the surface. Furthermore, the π-A and DV-A isotherms featured large hysteresis loops for the surfactant that contained a small amount of Hel 13-5 during compression and successive expansion cycling. To elucidate the morphology, the phase behavior was visualized in situ at the air-water interface by means of fluorescence microscopy; the images suggested less effective interactions between Hel 13-5 and the unsaturated PC in eggPC despite the similarity of their monolayer properties.

  16. Surfactant protein D is proatherogenic in mice

    DEFF Research Database (Denmark)

    Sørensen, Grith Lykke; Madsen, Jens; Kejling, Karin

    2006-01-01

    Surfactant protein D (SP-D) is an important innate immune defense molecule that mediates clearance of pathogens and modulates the inflammatory response. Moreover, SP-D is involved in lipid homeostasis, and pulmonary accumulation of phospholipids has previously been observed in SP-D-deficient (Spd...

  17. Biophysical inhibition of synthetic vs. naturally-derived pulmonary surfactant preparations by polymeric nanoparticles.

    Science.gov (United States)

    Beck-Broichsitter, Moritz; Ruppert, Clemens; Schmehl, Thomas; Günther, Andreas; Seeger, Werner

    2014-01-01

    Reasonable suspicion has accumulated that inhaled nano-scale particulate matter influences the biophysical function of the pulmonary surfactant system. Hence, it is evident to provide novel insights into the extent and mechanisms of nanoparticle-surfactant interactions in order to facilitate the fabrication of safe nanomedicines suitable for pulmonary applications. Negatively- and positively-charged poly(styrene) nanoparticles (diameters of ~100nm) served as model carriers. Nanoparticles were incubated with several synthetic and naturally-derived pulmonary surfactants to characterize the sensitivity of each preparation to biophysical inactivation. Changes in surface properties (i.e. adsorption and dynamic surface tension behavior) were monitored in a pulsating bubble surfactometer. Both nanoparticle formulations revealed a dose-dependent influence on the biophysical behavior of all investigated pulmonary surfactants. However, the surfactant sensitivity towards inhibition depended on both the carrier type, where negatively-charged nanoparticles showed increased inactivation potency compared to their positively-charged counterparts, and surfactant composition. Among the surfactants tested, synthetic mixtures (i.e. phospholipids, phospholipids supplemented with surfactant protein B, and Venticute®) were more susceptible to surface-activity inhibition as the more complex naturally-derived preparations (i.e. Alveofact® and large surfactant aggregates isolated from rabbit bronchoalveolar lavage fluid). Overall, nanoparticle characteristics and surfactant constitution both influence the extent of biophysical inhibition of pulmonary surfactants.

  18. BINDING ISOTHERMS SURFACTANT-PROTEINS

    Directory of Open Access Journals (Sweden)

    Elena Irina Moater

    2011-12-01

    Full Text Available The interactions between surfactants and proteins shows some similarities with interactions between surfactants and polymers, but the hydrophobic amphoteric nature of proteins and their secondary and tertiary structure components make them different from conventional polymer systems. Many studies from the past about surfactant - proteins bonding used the dialysis techniques. Other techniques used to determine the binding isotherm, included ultrafiltration, ultracentrifugation, potentiometry, ion-selective electrode method and surface tension. High affinity isotherms which are typical of an anionic surfactant - protein bonding, exhibit an initial increase steep followed by a slow growth region and then a vertical growth above a certain concentration. This isotherm is typical of ionic surfactant to protein binding. Often the high affinity initial bond appears at very low concentrations of surfactant and therefore in some protein-surfactant systems, the exact shape of the isotherm in this region may be missing. The surfactant - protein binding is influenced by a number of variables such as the nature and chain length of surfactant, pH, ionic strength, temperature, nature of this protein and additives.

  19. The Role of Surfactant in Lung Disease and Host Defense against Pulmonary Infections.

    Science.gov (United States)

    Han, SeungHye; Mallampalli, Rama K

    2015-05-01

    Pulmonary surfactant is essential for life as it lines the alveoli to lower surface tension, thereby preventing atelectasis during breathing. Surfactant is enriched with a relatively unique phospholipid, termed dipalmitoylphosphatidylcholine, and four surfactant-associated proteins, SP-A, SP-B, SP-C, and SP-D. The hydrophobic proteins, SP-B and SP-C, together with dipalmitoylphosphatidylcholine, confer surface tension-lowering properties to the material. The more hydrophilic surfactant components, SP-A and SP-D, participate in pulmonary host defense and modify immune responses. Specifically, SP-A and SP-D bind and partake in the clearance of a variety of bacterial, fungal, and viral pathogens and can dampen antigen-induced immune function of effector cells. Emerging data also show immunosuppressive actions of some surfactant-associated lipids, such as phosphatidylglycerol. Conversely, microbial pathogens in preclinical models impair surfactant synthesis and secretion, and microbial proteinases degrade surfactant-associated proteins. Deficiencies of surfactant components are classically observed in the neonatal respiratory distress syndrome, where surfactant replacement therapies have been the mainstay of treatment. However, functional or compositional deficiencies of surfactant are also observed in a variety of acute and chronic lung disorders. Increased surfactant is seen in pulmonary alveolar proteinosis, a disorder characterized by a functional deficiency of the granulocyte-macrophage colony-stimulating factor receptor or development of granulocyte-macrophage colony-stimulating factor antibodies. Genetic polymorphisms of some surfactant proteins such as SP-C are linked to interstitial pulmonary fibrosis. Here, we briefly review the composition, antimicrobial properties, and relevance of pulmonary surfactant to lung disorders and present its therapeutic implications.

  20. Intrinsic structural differences in the N-terminal segment of pulmonary surfactant protein SP-C from different species

    DEFF Research Database (Denmark)

    Plasencia, I; Rivas, L; Casals, C

    2001-01-01

    Predictive studies suggest that the known sequences of the N-terminal segment of surfactant protein SP-C from animal species have an intrinsic tendency to form beta-turns, but there are important differences on the probable location of these motifs in different SP-C species. Our hypothesis...... is that intrinsic structural determinants of the sequence of the N-terminal region of SP-C could define conformation, acylation and perhaps surface properties of the mature protein. To test this hypothesis we have synthesized peptides corresponding to the 13-residue N-terminal sequence of porcine and canine SP-C......-terminal end of SP-C may modulate these intrinsic conformational features and the changes induced could be important for the development of its surface activity. Udgivelsesdato: 2001-May...

  1. Biophysicochemical Interaction of a Clinical Pulmonary Surfactant with Nanoalumina.

    Science.gov (United States)

    Mousseau, F; Le Borgne, R; Seyrek, E; Berret, J-F

    2015-07-01

    We report on the interaction of pulmonary surfactant composed of phospholipids and proteins with nanometric alumina (Al2O3) in the context of lung exposure and nanotoxicity. We study the bulk properties of phospholipid/nanoparticle dispersions and determine the nature of their interactions. The clinical surfactant Curosurf, both native and extruded, and a protein-free surfactant are investigated. The phase behavior of mixed surfactant/particle dispersions was determined by optical and electron microscopy, light scattering, and zeta potential measurements. It exhibits broad similarities with that of strongly interacting nanosystems such as polymers, proteins or particles, and supports the hypothesis of electrostatic complexation. At a critical stoichiometry, micron-sized aggregates arising from the association between oppositely charged vesicles and nanoparticles are formed. Contrary to the models of lipoprotein corona or of particle wrapping, our work shows that vesicles maintain their structural integrity and trap the particles at their surfaces. The agglomeration of particles in surfactant phase is a phenomenon of importance that could change the interactions of the particles with lung cells.

  2. Water repellency induced by pulmonary surfactants.

    Science.gov (United States)

    Hills, B A

    1982-04-01

    1. Pure cotton fabric was partially carboxylated to produce a tough, porous, hydrophilic sub-phase to stimulate the epithelial membrane of the alveolar wall from a permeability standpoint. 2. Two of the predominant pulmonary surfactants, dipalmitoyl lecithin (DPL) and dipalmitoyl phosphatidylethanolamine (DPPE), were found to inhibit wetting of this synthetic membrane and of human cutaneous epithelium as manifest by a large contact angle. 3. When treated with DPL at physiological concentrations, the porous synthetic membrane was found to support a head of saline well in excess of systolic pulmonary artery pressure with no penetration and could do so for periods well in excess of 1 hr; untreated control samples allowed almost immediate fluid filtration. 4. Filtration could be initiated in the DPL-treated membranes by wetting the reverse side, confirming that the threshold pressure for fluid penetration was afforded by capillarity and, hence, by water repellency induced by the surfactant. 5. Water repellency induced by the amphoteric surfactants occurring naturally in the lung is discussed as a possible factor contributing to the pressure threshold to be exceeded for alveolar oedema to form. 6. Evidence is reviewed and several advantages discussed for the implied concept of an essentially dry lining to the alveolus with a discontinuous liquid layer largely confined to convex corners which could slowly resolve any oedema by surface forces.

  3. Correlation of pulmonary surfactant protein B, C and neonatal respiratory distress syndrome%肺表面蛋白B、C与新生儿呼吸窘迫综合征相关性研究进展

    Institute of Scientific and Technical Information of China (English)

    新春

    2015-01-01

    新生儿呼吸窘迫综合征(neonatal respiratory distress syndrome,NRDS)是新生儿较常见的危重症之一,其发病与肺表面蛋白(surfactant protein,SP)基因变异有密切相关.SP是肺表面活性物质(pul-monary surfactant,PS)的重要组成部分,在肺表面活性物质的结构、代谢、功能方面起重要作用.SP-B和SP-C在PS中极为重要,有密切关联.研究其等位基因变异与NRDS的关系有助于早期基因干预,促进临床诊断和治疗,对降低新生儿病死率具有长远的意义.%Neonatal respiratory distress syndrome is one of the common critically ill newborn's disease, the pathogenesis of which is closely related to gene mutation of the pulmonary suffactant protein(SP).Surfactant protein is an important component of the pulmonary surfactant, which plays an important role in the structure, metabolism, and function of pulmonary surfactant.SP-B and SP-C in pulmonary surfactant is extremely important and closely related to each other.Study on relationship between the SP gene allelic variation and neonatal respiratory distress syndrome could contribute to early genetic intervention, promote the clinical diagnosis and treatment, and bring far-reaching significance to reduce the neonatal mortality rate.

  4. Acidic pH triggers conformational changes at the NH2-terminal propeptide of the precursor of pulmonary surfactant protein B to form a coiled coil structure.

    Science.gov (United States)

    Bañares-Hidalgo, A; Pérez-Gil, J; Estrada, P

    2014-07-01

    Pulmonary surfactant protein SP-B is synthesized as a larger precursor, proSP-B. We report that a recombinant form of human SP-BN forms a coiled coil structure at acidic pH. The protonation of a residue with pK=4.8±0.06 is the responsible of conformational changes detected by circular dichroism and intrinsic fluorescence emission. Sedimentation velocity analysis showed protein oligomerisation at any pH condition, with an enrichment of the species compatible with a tetramer at acidic pH. Low 2,2,2,-trifluoroethanol concentration promoted β-sheet structures in SP-BN, which bind Thioflavin T, at acidic pH, whereas it promoted coiled coil structures at neutral pH. The amino acid stretch predicted to form β-sheet parallel association in SP-BN overlaps with the sequence predicted by several programs to form coiled coil structure. A synthetic peptide ((60)W-E(85)) designed from the sequence of the amino acid stretch of SP-BN predicted to form coiled coil structure showed random coil conformation at neutral pH but concentration-dependent helical structure at acidic pH. Sedimentation velocity analysis of the peptide indicated monomeric state at neutral pH (s20, w=0.55S; Mr~3kDa) and peptide association (s20, w=1.735S; Mr=~14kDa) at acidic pH, with sedimentation equilibrium fitting to a Monomer-Nmer-Mmer model with N=6 and M=4 (Mr=14692Da). We propose that protein oligomerisation through coiled-coil motifs could then be a general feature in the assembly of functional units in saposin-like proteins in general and in the organization of SP-B in a functional surfactant, in particular. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Genetic and environmental influences of surfactant protein D serum levels

    DEFF Research Database (Denmark)

    Sorensen, G.L.; Hjelmborg, J.V.; Kyvik, K.O.

    2006-01-01

    The collectin surfactant protein D (SP-D) is an important component of the pulmonary innate immune system, but SP-D is also present on extrapulmonary epithelial surfaces and in serum, where it has been used as a biomarker for pulmonary disease states. In this study, we investigate the mechanisms ...

  6. The importance of surfactant proteins-New aspects on macrophage phagocytosis.

    Science.gov (United States)

    Tschernig, Thomas; Veith, Nils T; Diler, Ebru; Bischoff, Markus; Meier, Carola; Schicht, Martin

    2016-11-01

    Surfactant and its components have multiple functions. The so called collectins are surfactant proteins which opsonize bacteria and improve pulmonary host defense via the phagocytosis and clearance of microorganisms and particles. In this special issue of the Annals of Anatomy a new surfactant protein, Surfactant Associated 3, is highlighted. As outlined in this mini review Surfactant Associated 3 is regarded as an enhancer of phagocytosis. In addition, the role played by SP-A is updated and open research questions raised.

  7. Inflammatory reaction and alterations of pulmonary surfactant in Pseudomonas Aeruginosa pneumonia in immunocompromised rats

    Institute of Scientific and Technical Information of China (English)

    瞿介明; 李倬哲; 何礼贤; 孙波; 陈雪华

    2002-01-01

    Pulmonary surfactant (PS) compromises lipids and surfactant proteins (SP) and lines on the alveolar air-liquid interface. It can reduce surface tension, prevent alveoli from collapse and reduce alveoli edema by disaturated dipalmitoylphosphatidylcholine.1 It also modulates the pulmonary immunology by SP-A and SP-D.2 In this study, we established a rat model of immunocompromised host (ICH) with pulmonary infection of Pseudomonas aeruginosa (P. aeruginosa), then studied its pulmonary inflammatory reaction and analyzed the concentration of lipids and SP-A in bronchoalveolar lavage fluid (BALF) during infection.

  8. Lung surfactant levels are regulated by Ig-Hepta/GPR116 by monitoring surfactant protein D.

    Directory of Open Access Journals (Sweden)

    Taku Fukuzawa

    Full Text Available Lung surfactant is a complex mixture of lipids and proteins, which is secreted from the alveolar type II epithelial cell and coats the surface of alveoli as a thin layer. It plays a crucial role in the prevention of alveolar collapse through its ability to reduce surface tension. Under normal conditions, surfactant homeostasis is maintained by balancing its release and the uptake by the type II cell for recycling and the internalization by alveolar macrophages for degradation. Little is known about how the surfactant pool is monitored and regulated. Here we show, by an analysis of gene-targeted mice exhibiting massive accumulation of surfactant, that Ig-Hepta/GPR116, an orphan receptor, is expressed on the type II cell and sensing the amount of surfactant by monitoring one of its protein components, surfactant protein D, and its deletion results in a pulmonary alveolar proteinosis and emphysema-like pathology. By a coexpression experiment with Sp-D and the extracellular region of Ig-Hepta/GPR116 followed by immunoprecipitation, we identified Sp-D as the ligand of Ig-Hepta/GPR116. Analyses of surfactant metabolism in Ig-Hepta(+/+ and Ig-Hepta(-/- mice by using radioactive tracers indicated that the Ig-Hepta/GPR116 signaling system exerts attenuating effects on (i balanced synthesis of surfactant lipids and proteins and (ii surfactant secretion, and (iii a stimulating effect on recycling (uptake in response to elevated levels of Sp-D in alveolar space.

  9. Lung surfactant levels are regulated by Ig-Hepta/GPR116 by monitoring surfactant protein D.

    Science.gov (United States)

    Fukuzawa, Taku; Ishida, Junji; Kato, Akira; Ichinose, Taro; Ariestanti, Donna Maretta; Takahashi, Tomoya; Ito, Kunitoshi; Abe, Jumpei; Suzuki, Tomohiro; Wakana, Shigeharu; Fukamizu, Akiyoshi; Nakamura, Nobuhiro; Hirose, Shigehisa

    2013-01-01

    Lung surfactant is a complex mixture of lipids and proteins, which is secreted from the alveolar type II epithelial cell and coats the surface of alveoli as a thin layer. It plays a crucial role in the prevention of alveolar collapse through its ability to reduce surface tension. Under normal conditions, surfactant homeostasis is maintained by balancing its release and the uptake by the type II cell for recycling and the internalization by alveolar macrophages for degradation. Little is known about how the surfactant pool is monitored and regulated. Here we show, by an analysis of gene-targeted mice exhibiting massive accumulation of surfactant, that Ig-Hepta/GPR116, an orphan receptor, is expressed on the type II cell and sensing the amount of surfactant by monitoring one of its protein components, surfactant protein D, and its deletion results in a pulmonary alveolar proteinosis and emphysema-like pathology. By a coexpression experiment with Sp-D and the extracellular region of Ig-Hepta/GPR116 followed by immunoprecipitation, we identified Sp-D as the ligand of Ig-Hepta/GPR116. Analyses of surfactant metabolism in Ig-Hepta(+/+) and Ig-Hepta(-/-) mice by using radioactive tracers indicated that the Ig-Hepta/GPR116 signaling system exerts attenuating effects on (i) balanced synthesis of surfactant lipids and proteins and (ii) surfactant secretion, and (iii) a stimulating effect on recycling (uptake) in response to elevated levels of Sp-D in alveolar space.

  10. Biomimicry of surfactant protein C.

    Science.gov (United States)

    Brown, Nathan J; Johansson, Jan; Barron, Annelise E

    2008-10-01

    Since the widespread use of exogenous lung surfactant to treat neonatal respiratory distress syndrome, premature infant survival and respiratory morbidity have dramatically improved. Despite the effectiveness of the animal-derived surfactant preparations, there still remain some concerns and difficulties associated with their use. This has prompted investigation into the creation of synthetic surfactant preparations. However, to date, no clinically used synthetic formulation is as effective as the natural material. This is largely because the previous synthetic formulations lacked analogues of the hydrophobic proteins of the lung surfactant system, SP-B and SP-C, which are critical functional constituents. As a result, recent investigation has turned toward the development of a new generation of synthetic, biomimetic surfactants that contain synthetic phospholipids along with a mimic of the hydrophobic protein portion of lung surfactant. In this Account, we detail our efforts in creating accurate mimics of SP-C for use in a synthetic surfactant replacement therapy. Despite SP-C's seemingly simple structure, the predominantly helical protein is extraordinarily challenging to work with given its extreme hydrophobicity and structural instability, which greatly complicates the creation of an effective SP-C analogue. Drawing inspiration from Nature, two promising biomimetic approaches have led to the creation of rationally designed biopolymers that recapitulate many of SP-C's molecular features. The first approach utilizes detailed SP-C structure-activity relationships and amino acid folding propensities to create a peptide-based analogue, SP-C33. In SP-C33, the problematic and metastable polyvaline helix is replaced with a structurally stable polyleucine helix and includes a well-placed positive charge to prevent aggregation. SP-C33 is structurally stable and eliminates the association propensity of the native protein. The second approach follows the same design

  11. Comparative characterization of pulmonary surfactant aggregates and alkaline phosphatase isozymes in human lung carcinoma tissue.

    Science.gov (United States)

    Iino, Nozomi; Matsunaga, Toshiyuki; Harada, Tsuyoshi; Igarashi, Seiji; Koyama, Iwao; Komoda, Tsugikazu

    2007-05-01

    Alkaline phosphatase (AP) isozymes are surfactant-associated proteins (SPs). Since several different AP isozymes have been detected in the pneumocytes of lung cancer patients, we attempted to identify the relationship between pulmonary surfactant aggregate subtypes and AP isozymes. Pulmonary surfactant aggregates were isolated from carcinoma and non-carcinoma tissues of patients with non-small cell carcinoma of the lung. Upon analysis, ultraheavy, heavy, and light surfactant aggregates were detected in the non-carcinoma tissues, but no ultraheavy surfactant aggregates were found in the carcinoma tissues. Surfactant-associated protein A (SP-A) was detected as two bands (a 27-kDa band and a 54-kDa band) in the ultraheavy, heavy, and light surfactant aggregates found in the non-carcinoma tissues. Although both SP-A bands were detected in the heavy and light surfactant aggregates from adenocarcinoma tissues, the 54-kDa band was not detected in squamous cell carcinoma tissues. Liver AP (LAP) was detected in the heavy and light surfactant aggregates from both non-carcinoma and squamous carcinoma tissues, but not in heavy surfactant aggregates from adenocarcinoma tissues. A larger amount of bone type AP (BAP) was found in light surfactant aggregate fractions from squamous cell carcinomas than those from adenocarcinoma tissues or non-carcinoma tissues from patients with either type of cancer. LAP, BAP, and SP-A were identified immunohistochemically in type II pneumocytes from non-carcinoma tissues and adenocarcinoma cells, but no distinct SP-A staining was observed in squamous cell carcinoma tissues. The present study has thus revealed several differences in pulmonary surfactant aggregates and AP isozymes between adenocarcinoma tissue and squamous cell carcinoma tissue.

  12. Composition, structure and mechanical properties define performance of pulmonary surfactant membranes and films.

    Science.gov (United States)

    Parra, Elisa; Pérez-Gil, Jesús

    2015-01-01

    The respiratory surface in the mammalian lung is stabilized by pulmonary surfactant, a membrane-based system composed of multiple lipids and specific proteins, the primary function of which is to minimize the surface tension at the alveolar air-liquid interface, optimizing the mechanics of breathing and avoiding alveolar collapse, especially at the end of expiration. The goal of the present review is to summarize current knowledge regarding the structure, lipid-protein interactions and mechanical features of surfactant membranes and films and how these properties correlate with surfactant biological function inside the lungs. Surfactant mechanical properties can be severely compromised by different agents, which lead to surfactant inhibition and ultimately contributes to the development of pulmonary disorders and pathologies in newborns, children and adults. A detailed comprehension of the unique mechanical and rheological properties of surfactant layers is crucial for the diagnostics and treatment of lung diseases, either by analyzing the contribution of surfactant impairment to the pathophysiology or by improving the formulations in surfactant replacement therapies. Finally, a short review is also included on the most relevant experimental techniques currently employed to evaluate lung surfactant mechanics, rheology, and inhibition and reactivation processes.

  13. High Oxygen Concentrations Adversely Affect the Performance of Pulmonary Surfactant.

    Science.gov (United States)

    Smallwood, Craig D; Boloori-Zadeh, Parnian; Silva, Maricris R; Gouldstone, Andrew

    2017-08-01

    Although effective in the neonatal population, exogenous pulmonary surfactant has not demonstrated a benefit in pediatric and adult subjects with hypoxic lung injury despite a sound physiologic rationale. Importantly, neonatal surfactant replacement therapy is administered in conjunction with low fractional FIO2 while pediatric/adult therapy is administered with high FIO2 . We suspected a connection between FIO2 and surfactant performance. Therefore, we sought to assess a possible mechanism by which the activity of pulmonary surfactant is adversely affected by direct oxygen exposure in in vitro experiments. The mechanical performance of pulmonary surfactant was evaluated using 2 methods. First, Langmuir-Wilhelmy balance was utilized to study the reduction in surface area (δA) of surfactant to achieve a low bound value of surface tension after repeated compression and expansion cycles. Second, dynamic light scattering was utilized to measure the size of pulmonary surfactant particles in aqueous suspension. For both experiments, comparisons were made between surfactant exposed to 21% and 100% oxygen. The δA of surfactant was 21.1 ± 2.0% and 35.8 ± 2.0% during exposure to 21% and 100% oxygen, respectively (P = .02). Furthermore, dynamic light-scattering experiments revealed a micelle diameter of 336.0 ± 12.5 μm and 280.2 ± 11.0 μm in 21% and 100% oxygen, respectively (P < .001), corresponding to a ∼16% decrease in micelle diameter following exposure to 100% oxygen. The characteristics of pulmonary surfactant were adversely affected by short-term exposure to oxygen. Specifically, surface tension studies revealed that short-term exposure of surfactant film to high concentrations of oxygen expedited the frangibility of pulmonary surfactant, as shown with the δA. This suggests that reductions in pulmonary compliance and associated adverse effects could begin to take effect in a very short period of time. If these findings can be demonstrated in vivo, a role for

  14. Induction of virulence gene expression in Staphylococcus aureus by pulmonary surfactant.

    Science.gov (United States)

    Ishii, Kenichi; Adachi, Tatsuo; Yasukawa, Jyunichiro; Suzuki, Yutaka; Hamamoto, Hiroshi; Sekimizu, Kazuhisa

    2014-04-01

    We performed a genomewide analysis using a next-generation sequencer to investigate the effect of pulmonary surfactant on gene expression in Staphylococcus aureus, a clinically important opportunistic pathogen. RNA sequence (RNA-seq) analysis of bacterial transcripts at late log phase revealed 142 genes that were upregulated >2-fold following the addition of pulmonary surfactant to the culture medium. Among these genes, we confirmed by quantitative reverse transcription-PCR analysis that mRNA amounts for genes encoding ESAT-6 secretion system C (EssC), an unknown hypothetical protein (NWMN_0246; also called pulmonary surfactant-inducible factor A [PsiA] in this study), and hemolysin gamma subunit B (HlgB) were increased 3- to 10-fold by the surfactant treatment. Among the major constituents of pulmonary surfactant, i.e., phospholipids and palmitate, only palmitate, which is the most abundant fatty acid in the pulmonary surfactant and a known antibacterial substance, stimulated the expression of these three genes. Moreover, these genes were also induced by supplementing the culture with detergents. The induction of gene expression by surfactant or palmitate was not observed in a disruption mutant of the sigB gene, which encodes an alternative sigma factor involved in bacterial stress responses. Furthermore, each disruption mutant of the essC, psiA, and hlgB genes showed attenuation of both survival in the lung and host-killing ability in a murine pneumonia model. These findings suggest that S. aureus resists membrane stress caused by free fatty acids present in the pulmonary surfactant through the regulation of virulence gene expression, which contributes to its pathogenesis within the lungs of the host animal.

  15. Composition, structure and mechanical properties define performance of pulmonary surfactant membranes and films

    DEFF Research Database (Denmark)

    Ortiz, Elisa Parra; Perez-Gil, Jesús

    2015-01-01

    The respiratory surface in the mammalian lung is stabilized by pulmonary surfactant, a membrane-based system composed of multiple lipids and specific proteins, the primary function of which is to minimize the surface tension at the alveolar air-liquid interface, optimizing the mechanics of breath......The respiratory surface in the mammalian lung is stabilized by pulmonary surfactant, a membrane-based system composed of multiple lipids and specific proteins, the primary function of which is to minimize the surface tension at the alveolar air-liquid interface, optimizing the mechanics...... of breathing and avoiding alveolar collapse, especially at the end of expiration. The goal of the present review is to summarize current knowledge regarding the structure, lipid-protein interactions and mechanical features of surfactant membranes and films and how these properties correlate with surfactant...... biological function inside the lungs. Surfactant mechanical properties can be severely compromised by different agents, which lead to surfactant inhibition and ultimately contributes to the development of pulmonary disorders and pathologies in newborns, children and adults. A detailed comprehension...

  16. Analysis of pulmonary surfactant by Fourier transform infrared spectroscopy after exposure to sevoflurane and isoflurane.

    Science.gov (United States)

    Vrbanović Mijatović, Vilena; Šerman, Ljiljana; Gamulin, Ozren

    2017-02-21

    Pulmonary surfactant, consisting primarily of phospholipids and four surfactant-specific proteins, is among the first structures that is exposed to inhalation anesthetics. Consequently, changes of pulmonary surfactant due to this exposure could cause respiratory complications after long anesthetic procedures. Fourier transform infrared (FTIR) spectroscopy was used to explore the effects of two inhalation anesthetics, sevoflurane and isoflurane, on a commercially available pulmonary surfactant. The research was primarily focused on the effect of anesthetics on the lipid component of the surfactant. Four different concentrations of anesthetics were added, and the doses were higher from the low clinical doses typically used. Recorded spectra were analyzed using principal component analysis, and the Student's t-test was performed to confirm the results. The exposure to both anesthetics induced similar changes, consistent with the increase of the anesthetic concentration. The most pronounced effect was on the hydrophilic head group of phospholipids, which is in agreement with the disruption of the hydrogen bond, caused by the anesthetics. A change in the band intensities of CH2 stretching vibrations, indicative of a disordering effect of anesthetics on the hydrophobic tails of phospholipids, was also observed. Changes induced by isoflurane appear to be more pronounced than those induced by sevoflurane. Furthermore, our results suggest that FTIR spectroscopy is a promising tool in studying anesthetic effects on pulmonary surfactant.

  17. Pulmonary surfactant adsorption is increased by hyaluronan or polyethylene glycol.

    Science.gov (United States)

    Taeusch, H William; Dybbro, Eric; Lu, Karen W

    2008-04-01

    In acute lung injuries, inactivating agents may interfere with transfer (adsorption) of pulmonary surfactants to the interface between air and the aqueous layer that coats the interior of alveoli. Some ionic and nonionic polymers reduce surfactant inactivation in vitro and in vivo. In this study, we tested directly whether an ionic polymer, hyaluronan, or a nonionic polymer, polyethylene glycol, enhanced adsorption of a surfactant used clinically. We used three different methods of measuring adsorption in vitro: a modified pulsating bubble surfactometer; a King/Clements device; and a spreading trough. In addition we measured the effects of both polymers on surfactant turbidity, using this assay as a nonspecific index of aggregation. We found that both hyaluronan and polyethylene glycol significantly increased the rate and degree of surfactant material adsorbed to the surface in all three assays. Hyaluronan was effective in lower concentrations (20-fold) than polyethylene glycol and, unlike polyethylene glycol, hyaluronan did not increase apparent aggregation of surfactant. Surfactant adsorption in the presence of serum was also enhanced by both polymers regardless of whether hyaluronan or polyethylene glycol was included with serum in the subphase or added to the surfactant applied to the surface. Therefore, endogenous polymers in the alveolar subphase, or exogenous polymers added to surfactant used as therapy, may both be important for reducing inactivation of surfactant that occurs with various lung injuries.

  18. Exogenous Pulmonary Surfactant as a Vehicle for Antimicrobials: Assessment of Surfactant-Antibacterial Interactions In Vitro

    Directory of Open Access Journals (Sweden)

    Alexei Birkun

    2014-01-01

    Full Text Available Owing to its unique surface-active properties, an exogenous pulmonary surfactant may become a promising drug delivery agent, in particular, acting as a vehicle for antibiotics in topical treatment of pneumonia. The purpose of this study was to assess a mutual influence of natural surfactant preparation and three antibiotics (amikacin, cefepime, and colistimethate sodium in vitro and to identify appropriate combination(s for subsequent in vivo investigations of experimental surfactant/antibiotic mixtures. Influence of antibiotics on surface-active properties of exogenous surfactant was assessed using the modified Pattle method. Effects of exogenous surfactant on antibacterial activity of antimicrobials against Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa were evaluated using conventional microbiologic procedures. Addition of amikacin or cefepime to surfactant had no significant influence on surface-active properties of the latter. Obvious reduction of surface-active properties was confirmed for surfactant/colistimethate composition. When suspended with antibiotics, surfactant either had no impact on their antimicrobial activity (amikacin or exerted mild to moderate influence (reduction of cefepime bactericidal activity and increase of colistimethate bacteriostatic activity against S. aureus and P. aeruginosa. Considering favorable compatibility profile, the surfactant/amikacin combination is advisable for subsequent investigation of joint surfactant/antibacterial therapy in animals with bacterial pneumonia.

  19. Biophysicochemical interaction of a clinical pulmonary surfactant with nano-alumina

    CERN Document Server

    Mousseau, F; Seyrek, E; Berret, J -F

    2015-01-01

    We report on the interaction of pulmonary surfactant composed of phospholipids and proteins with nanometric alumina (Al2O3) in the context of lung exposure and nanotoxicity. We study the bulk properties of phospholipid/nanoparticle dispersions and determine the nature of their interactions. The clinical surfactant Curosurf, both native and extruded, and a protein-free surfactant are investigated. The phase behavior of mixed surfactant/particle dispersions was determined by optical and electron microscopy, light scattering and zeta potential measurements. It exhibits broad similarities with that of strongly interacting nanosystems such as polymers, proteins or particles, and supports the hypothesis of electrostatic complexation. At a critical stoichiometry, micron sized aggregates arising from the association between oppositely charged vesicles and nanoparticles are formed. Contrary to the models of lipoprotein corona or of particle wrapping, our work shows that vesicles maintain their structural integrity and...

  20. Pulmonary Surfactants for Acute and Chronic Lung Diseases (Part II

    Directory of Open Access Journals (Sweden)

    O. A. Rozenberg

    2014-01-01

    Full Text Available Part 2 of the review considers the problem of surfactant therapy for acute respiratory distress syndrome (ARDS in adults and young and old children. It gives information on the results of surfactant therapy and prevention of ARDS in patients with severe concurrent trauma, inhalation injuries, complications due to complex expanded chest surgery, or severe pneumonias, including bilateral pneumonia in the presence of A/H1N1 influenza. There are data on the use of a surfactant in obstetric care and prevention of primary graft dysfunction during lung transplantation. The results of longterm use of surfactant therapy in Russia, suggesting that death rates from ARDS may be substantially reduced (to 20% are discussed. Examples of surfactant therapy for other noncritical lung diseases, such as permanent athelectasis, chronic obstructive pulmonary diseases, and asthma, as well tuberculosis, are also considered.

  1. Pulmonary infections in swine induce altered porcine surfactant protein D expression and localization to dendritic cells in bronchial-associated lymphoid tissue

    DEFF Research Database (Denmark)

    Sørensen, C.M.; Holmskov, U.; Aalbæk, B.;

    2005-01-01

    Surfactant protein D (SP-D) is a pattern-recognition molecule of the innate immune system that recognizes various microbial surface-specific carbohydrate and lipid patterns. In vitro data has suggested that this binding may lead to increased microbial association with macrophages and dendritic...... among pSP-D, pathogens, phagocytic cells and dendritic cells. Lung tissue was collected from experimental and natural bronchopneumonias caused by Actinobacillus pleuropneumoniae or Staphylococcus aureus, and from embolic and diffuse interstitial pneumonia, caused by Staph. aureus or Arcanobacterium......SP-D through the specialized M cells overlying (BALT). In conclusion, we have shown that pSP-D expression in the lung surfactant is induced by bacterial infection by an aerogenous route rather than by a haematogenous route, and that the protein interacts specifically with alveolar macrophages...

  2. Surfactant protein D is proatherogenic in mice

    DEFF Research Database (Denmark)

    Sorensen, Grith L; Madsen, Jens; Kejling, Karin

    2006-01-01

    Surfactant protein D (SP-D) is an important innate immune defense molecule that mediates clearance of pathogens and modulates the inflammatory response. Moreover, SP-D is involved in lipid homeostasis, and pulmonary accumulation of phospholipids has previously been observed in SP-D-deficient (Spd......-/-) mice. Atherogenesis involves both inflammation and lipid deposition, and we investigated the role of SP-D in the development of atherosclerosis. SP-D synthesis was localized to vascular endothelial cells. Atherosclerotic lesion areas were 5.6-fold smaller in the aortic roots in Spd-/- mice compared...... with wild-type C57BL/6N mice on an atherogenic diet. HDL cholesterol (HDL-C) was significantly elevated in Spd-/- mice. Treatment of Spd-/- mice with a recombinant fragment of human SP-D resulted in decreases of HDL-C (21%) as well as total cholesterol (26%), and LDL cholesterol (28%). Plasma TNF...

  3. Surfactant apoprotein in nonmalignant pulmonary disorders.

    OpenAIRE

    Singh, G.; Katyal, S. L.

    1980-01-01

    Formalin-fixed, paraffin-embedded lungs exhibiting a variety of nonmalignant disorders were studied by immunoperoxidase staining using antibodies specific for surfactant apoprotein, IgG, IgM, IgA, albumin, fibrinogen, and lysozyme. Normal Type II pneumocytes showed staining for surfactant apoprotein in the perinuclear region only. The extent and intensity of staining for apoprotein was markedly increased in reactive Type II pneumocytes. This increase appeared to be a nonspecific reaction to l...

  4. The adsorption of biomolecules to multi-walled carbon nanotubes is influenced by both pulmonary surfactant lipids and surface chemistry

    Directory of Open Access Journals (Sweden)

    Yan Bing

    2010-12-01

    Full Text Available Abstract Background During production and processing of multi-walled carbon nanotubes (MWCNTs, they may be inhaled and may enter the pulmonary circulation. It is essential that interactions with involved body fluids like the pulmonary surfactant, the blood and others are investigated, particularly as these interactions could lead to coating of the tubes and may affect their chemical and physical characteristics. The aim of this study was to characterize the possible coatings of different functionalized MWCNTs in a cell free environment. Results To simulate the first contact in the lung, the tubes were coated with pulmonary surfactant and subsequently bound lipids were characterized. The further coating in the blood circulation was simulated by incubating the tubes in blood plasma. MWCNTs were amino (NH2- and carboxyl (-COOH-modified, in order to investigate the influence on the bound lipid and protein patterns. It was shown that surfactant lipids bind unspecifically to different functionalized MWCNTs, in contrast to the blood plasma proteins which showed characteristic binding patterns. Patterns of bound surfactant lipids were altered after a subsequent incubation in blood plasma. In addition, it was found that bound plasma protein patterns were altered when MWCNTs were previously coated with pulmonary surfactant. Conclusions A pulmonary surfactant coating and the functionalization of MWCNTs have both the potential to alter the MWCNTs blood plasma protein coating and to determine their properties and behaviour in biological systems.

  5. The relationship between vitamin A and pulmonary surfactant protein with neonatal pulmonary function%维生素A和肺表面活性蛋白与新生儿肺功能的关系

    Institute of Scientific and Technical Information of China (English)

    孙灿; 娄岩; 付瑜; 朱佳俊; 赵晴; 车千红; 孔娟

    2015-01-01

    目的:研究人体内维生素A( vitamin A,VA)水平与肺表面活性蛋白( surfactant pro-teins,SP)-B、SP-C的相关性,以及对新生儿肺发育和肺功能的影响。方法收集170例孕妇血清及所产新生儿的脐带血清,用ELISA试剂盒检测母亲和新生儿血清中VA水平及新生儿脐带血清中SP-B、SP-C的含量。在新生儿出生6个月后,通过标准的电话问卷调查进行一次随访,内容为生后半年内有无呼吸道感染及感染的次数,以此来评估新生儿生后半年内肺功能的情况。结果(1)新生儿脐带血中VA含量与母亲血清中VA含量呈正相关(r=0.866,P<0.05);(2)新生儿脐带血中VA含量与SP-B、SP-C含量呈正相关(r=0.817,P<0.05),且不受其母亲产前VA水平影响;(3)随访发现,170例婴儿中有3例在半年内因肺炎住院1次及以上,但无呼吸窘迫综合征发生。结论 VA可以作为新生儿肺成熟的重要生物标记物,通过检测产前孕妇的VA水平,适当补充VA,可以提高新生儿SP-B、SP-C的含量,提高新生儿在以后生长发育中的肺功能。%Objective To investigate the correlation between vitamin A and surfactant protein (SP)-B, SP-C in human body,and to explore the effects on lung development and pulmonary function of neonates. Methods We collected the blood samples of 170 pregnant women and umbilical cord serum of their neonatal babies. The levels of vitamin A in pregnant women and their neonatal babies,and the levels of SP-B and SP-C in neonatal umbilical cord serum were detected by ELISA. We conducted a follow-up by standard telephone questionnaire,which we concerned was the number of respiratory tract infection within six months,in order to assess the neonatal pulmonary functions. Results (1) There was a positive correlation between the vitamin A levels in neonatal umbilical cord blood and in the blood of pregnant women(r=0. 866,P<0. 05). (2) There was a positive correlation between the vitamin A levels in

  6. Control of pulmonary surfactant secretion from type II pneumocytes isolated from the lizard Pogona vitticeps.

    Science.gov (United States)

    Wood, P G; Lopatko, O V; Orgeig, S; Codd, J R; Daniels, C B

    1999-12-01

    Pulmonary surfactant, a mixture consisting of lipids and proteins and secreted by type II cells, functions to reduce the surface tension of the fluid lining of the lung, and thereby decreases the work of breathing. In mammals, surfactant secretion appears to be influenced primarily by the sympathetic nervous system and changes in ventilatory pattern. The parasympathetic nervous system is not believed to affect surfactant secretion in mammals. Very little is known about the factors that control surfactant secretion in nonmammalian vertebrates. Here, a new methodology for the isolation and culture of type II pneumocytes from the lizard Pogona vitticeps is presented. We examined the effects of the major autonomic neurotransmitters, epinephrine (Epi) and ACh, on total phospholipid (PL), disaturated PL (DSP), and cholesterol (Chol) secretion. At 37 degrees C, only Epi stimulated secretion of total PL and DSP from primary cultures of lizard type II cells, and secretion was blocked by the beta-adrenoreceptor antagonist propranolol. Neither of the agonists affected Chol secretion. At 18 degrees C, Epi and ACh both stimulated DSP and PL secretion but not Chol secretion. The secretion of surfactant Chol does not appear to be under autonomic control. It appears that the secretion of surfactant PL is predominantly controlled by the autonomic nervous system in lizards. The sympathetic nervous system may control surfactant secretion at high temperatures, whereas the parasympathetic nervous system may predominate at lower body temperatures, stimulating surfactant secretion without elevating metabolic rate.

  7. Cholesterol rules: direct observation of the coexistence of two fluid phases in native pulmonary surfactant membranes at physiological temperatures

    DEFF Research Database (Denmark)

    Bernardino de la Serna, Jorge; Perez-Gil, Jesus; Simonsen, Adam C

    2004-01-01

    Pulmonary surfactant, the lipid-protein material that stabilizes the respiratory surface of the lungs, contains approximately equimolar amounts of saturated and unsaturated phospholipid species and significant proportions of cholesterol. Such lipid composition suggests that the membranes taking...... part in the surfactant structures could be organized heterogeneously in the form of inplane domains, originating from particular distributions of specific proteins and lipids. Here we report novel results concerning the lateral organization of bilayer membranes made of native pulmonary surfactant where...... of this material is naturally designed to be at the "edge" of a lateral structure transition under physiological conditions, likely providing particular structural and dynamic properties for its mechanical function. The observed lateral structure in native pulmonary surfactant membranes is dramatically affected...

  8. Analysis of pulmonary surfactant in rat lungs after inhalation of nanomaterials: Fullerenes, nickel oxide and multi-walled carbon nanotubes.

    Science.gov (United States)

    Kadoya, Chikara; Lee, Byeong-Woo; Ogami, Akira; Oyabu, Takako; Nishi, Ken-ichiro; Yamamoto, Makoto; Todoroki, Motoi; Morimoto, Yasuo; Tanaka, Isamu; Myojo, Toshihiko

    2016-01-01

    The health risks of inhalation exposure to engineered nanomaterials in the workplace are a major concern in recent years, and hazard assessments of these materials are being conducted. The pulmonary surfactant of lung alveoli is the first biological entity to have contact with airborne nanomaterials in inhaled air. In this study, we retrospectively evaluated the pulmonary surfactant components of rat lungs after a 4-week inhalation exposure to three different nanomaterials: fullerenes, nickel oxide (NiO) nanoparticles and multi-walled carbon nanotubes (MWCNT), with similar levels of average aerosol concentration (0.13-0.37 mg/m(3)). Bronchoalveolar lavage fluid (BALF) of the rat lungs stored after previous inhalation studies was analyzed, focusing on total protein and the surfactant components, such as phospholipids and surfactant-specific SP-D (surfactant protein D) and the BALF surface tension, which is affected by SP-B and SP-C. Compared with a control group, significant changes in the BALF surface tension and the concentrations of phospholipids, total protein and SP-D were observed in rats exposed to NiO nanoparticles, but not in those exposed to fullerenes. Surface tension and the levels of surfactant phospholipids and proteins were also significantly different in rats exposed to MWCNTs. The concentrations of phospholipids, total protein and SP-D and BALF surface tension were correlated significantly with the polymorphonuclear neutrophil counts in the BALF. These results suggest that pulmonary surfactant components can be used as measures of lung inflammation.

  9. Transient exposure of pulmonary surfactant to hyaluronan promotes structural and compositional transformations into a highly active state.

    Science.gov (United States)

    Lopez-Rodriguez, Elena; Cruz, Antonio; Richter, Ralf P; Taeusch, H William; Pérez-Gil, Jesús

    2013-10-11

    Pulmonary surfactant is a lipid-protein complex that lowers surface tension at the respiratory air-liquid interface, stabilizing the lungs against physical forces tending to collapse alveoli. Dysfunction of surfactant is associated with respiratory pathologies such as acute respiratory distress syndrome or meconium aspiration syndrome where naturally occurring surfactant-inhibitory agents such as serum, meconium, or cholesterol reach the lung. We analyzed the effect of hyaluronan (HA) on the structure and surface behavior of pulmonary surfactant to understand the mechanism for HA-promoted surfactant protection in the presence of inhibitory agents. In particular, we found that HA affects structural properties such as the aggregation state of surfactant membranes and the size, distribution, and order/packing of phase-segregated lipid domains. These effects do not require a direct interaction between surfactant complexes and HA and are accompanied by a compositional reorganization of large surfactant complexes that become enriched with saturated phospholipid species. HA-exposed surfactant reaches very high efficiency in terms of rapid and spontaneous adsorption of surfactant phospholipids at the air-liquid interface and shows significantly improved resistance to inactivation by serum or cholesterol. We propose that physical effects pertaining to the formation of a meshwork of interpenetrating HA polymer chains are responsible for the changes in surfactant structure and composition that enhance surfactant function and, thus, resistance to inactivation. The higher resistance of HA-exposed surfactant to inactivation persists even after removal of the polymer, suggesting that transient exposure of surfactant to polymers like HA could be a promising strategy for the production of more efficient therapeutic surfactant preparations.

  10. Pulmonary infections in swine induce altered porcine surfactant protein D expression and localization to dendritic cells in bronchial-associated lymphoid tissue

    DEFF Research Database (Denmark)

    Sørensen, C.M.; Holmskov, U.; Aalbæk, B.

    2005-01-01

    and with dendritic cells in microbial-induced BALT. The function of the interaction between pSP-D and dendritic cells in BALT remain unclear, but pSP-D could represent a link between the innate and adaptive immune system, facilitating the bacterial antigen presentation by dendritic cells in BALT.......Surfactant protein D (SP-D) is a pattern-recognition molecule of the innate immune system that recognizes various microbial surface-specific carbohydrate and lipid patterns. In vitro data has suggested that this binding may lead to increased microbial association with macrophages and dendritic...

  11. Study on Pulmonary Surfactant of Sudden Death of Infant

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To find the pathogenesis of sudden infant death syndrome (S IDS) from changes of pulmonurry surfactant. Methods By means of thin-layer ckromatography technique, surfactant in whole lung specimens of 10 infants with SIDS and 10 control infants without SIDS (dead of nonrespiratory diseases ) were examined qualitatively and quantitatively. Results Eleven components in pulmonary surfactant were examined qualitatively, including lysophosphatidylcholine , sphingomyelin , phosphatidylcholine , phosphatidylserine , phosphatidylinositol , phos phatidylethanolamine , phosphatidylglycerol , diphosphatidylylycerol , phosphatidic acid, cholesterol and neutral lipids. Quantitative examination showed that the amount of surfactant of whole lung specimens in sudden death group [-(8.9±1.0) rng/g wet lung weight] was significantly less than that in control group [-(12. 6±1.4) mg/g uet lung weight, P<0. 01]. Qualitative variance showed that the percentages of phosphatidylcholine (49. 4 % ± 2. 0 % ) and phosphatidylylycerol ( 2. 6 % ± 0. 7 % ) decreased markedly in sudden death group compared with those in control group (61.5 % ± 3. 0 % and 4.3 % ±1. 5%, P < 0. 01 ). Conclusion Before death there is serions defect on metabolism of pulmonary surfactant in sudden death infants, with the amount decreasing and the ratio of its components being disturbed, which is one of the important pathogenies of SIDS.

  12. Study on Pulmonary Surfactant of Sudden Death of Infant

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To find the pathogenesis of sudden infant death syndrome (S IDS) from changes of pulmonurry surfactant. Methods By means of thin-layer ckromatography technique, surfactant in whole lung specimens of 10 infants with SIDS and 10 control infants without SIDS (dead of nonrespiratory diseases ) were examined qualitatively and quantitatively. Results Eleven components in pulmonary surfactant were examined qualitatively, including lysophosphatidylcholine , sphingomyelin , phosphatidylcholine , phosphatidylserine , phosphatidylinositol , phos phatidylethanolamine , phosphatidylglycerol , diphosphatidylylycerol , phosphatidic acid, cholesterol and neutral lipids. Quantitative examination showed that the amount of surfactant of whole lung specimens in sudden death group [-(8.9±1.0) rng/g wet lung weight] was significantly less than that in control group [-(12. 6±1.4) mg/g uet lung weight, P<0. 01]. Qualitative variance showed that the percentages of phosphatidylcholine (49. 4 % ± 2. 0 % ) and phosphatidylylycerol ( 2. 6 % ± 0. 7 % ) decreased markedly in sudden death group compared with those in control group (61.5 % ± 3. 0 % and 4.3 % ±1. 5%, P < 0. 01 ). Conclusion Before death there is serions defect on metabolism of pulmonary surfactant in sudden death infants, with the amount decreasing and the ratio of its components being disturbed, which is one of the important pathogenies of SIDS.

  13. Surfactant phospholipids and proteins in lung defence%肺防御系统中的表面磷脂酶和蛋白

    Institute of Scientific and Technical Information of China (English)

    Haagsman HP; Herias V; van Eijk M

    2003-01-01

    Pulmonary surfactant comprises two hydrophobic proteins SP-B and SP-C, which are important forthe adsorption and spreading of the surfactant film at the air-liquid interface. Besides the hydrophobic proteins two other surfactant proteins have been described: SP-A and SP-D. These proteins are members of a family

  14. The Physical Properties of a Lavage Mixture of Pulmonary Surfactant, Perfluorodecaline, and Methylprednisolone (Perfactant Lavage)

    Science.gov (United States)

    2014-05-09

    surfactant , perfluorodecaline, and methylprednisolone (perfectant lavage) Timothy F. Haley, MD, LTC, MC Timothy F. Haley, MD, LTC, MC, USA Division...release: distribution unlimited Purpose: To characterize the physical properties of a lavage mixture of pulmonary surfactant , perfluorocarbon and...MIXTURE OF PULMONARY SURFACTANT , PERFLUORODECALINE AND METHYLPREDNISOLONE (PERFACTANT LAVAGE) INVESTIGATOR: Timothy F. Haley, MD, LTC, MC, USA

  15. 肺泡表面相关蛋白A和D研究进展与意义%Study progress and significance of pulmonary surfactant-associated protein A and D

    Institute of Scientific and Technical Information of China (English)

    胡华; 迟晶宇

    2010-01-01

    Pulmonary surfactant-associated protein A (SP-A) and SP-D belong to lectin family,have correlation with pulmonary innate immunity, combine with a variety of sugar molecules on the microorganism surfaces and intracellular nucleic acid molecules, mediate immune function, promoteclearance and localization of bacteria,viruses, fungi, and apoptotic and necrotic cells. They can interact with molecules or receptors on the immune cell surface, regulate the functions of dendritic cells, macrophages and other immune cells. Many researches about the levels of SP-A and SP-D in alveolar lavage fluid, blood and other body fluids show that SP-A and SP-D are related to multiple pulmonary inflammation, infectious diseases. In addition,researchers have found that correlated recombinant protein has a therapeutic effect on pulmonary infectious diseases mice with SP-A and SP-D defects. This review sums up the current study of SP-A and SP-D and the relationship between various diseases and them.%肺泡表面相关蛋白A(pulmonary surfactant-associated protein A,SP-A)、SP-D属于凝集索家族,与肺的天然免疫有着很大的相关性,能够与多种微生物表面的糖类分子以及细胞内核酸分子相结合,介导免疫功能,促使细菌、病毒、真菌以及凋亡和坏死细胞的清除和局限,同时能够与免疫细胞表面分子或者受体结合,调节树突状细胞、巨噬细胞等免疫细胞的功能.许多研究学者关于SP-A和SP-D在肺泡灌洗液、血液及其他体液中的水平有着深刻的研究,证明了SP-A和SP-D与肺内多种炎症、感染性疾病有关.除此之外,有研究学者发现相关重组蛋白在SP-A和SP-D缺陷的肺部感染性疾病的小鼠中具有一定的治疗作用.本文总结了SP-A和SP-D目前研究的深度以及和多种疾病的关系.

  16. Regulation of pulmonary surfactant secretion in the developing lizard, Pogona vitticeps.

    Science.gov (United States)

    Sullivan, Lucy C; Orgeig, Sandra; Daniels, Christopher B

    2002-11-01

    Pulmonary surfactant is a mixture of lipids and proteins that is secreted by alveolar type II cells in the lungs of all air-breathing vertebrates. Pulmonary surfactant functions to reduce the surface tension in the lungs and, therefore, reduce the work of breathing. In mammals, the embryonic maturation of the surfactant system is controlled by a host of factors, including glucocorticoids, thyroid hormones and autonomic neurotransmitters. We have used a co-culture system of embryonic type II cells and lung fibroblasts to investigate the ability of dexamethasone, tri-iodothyronine (T(3)), adrenaline and carbamylcholine (carbachol) to stimulate the cellular secretion of phosphatidylcholine in the bearded dragon (Pogona vitticeps) at day 55 (approx. 92%) of incubation and following hatching. Adrenaline stimulated surfactant secretion both before and after hatching, whereas carbachol stimulated secretion only at day 55. Glucocorticoids and triiodothyronine together stimulated secretion at day 55 but did not after hatching. Therefore, adrenaline, carbachol, dexamethasone and T(3), are all involved in the development of the surfactant system in the bearded dragon. However, the efficacy of the hormones is attenuated during the developmental process. These differences probably relate to the changes in the cellular environment during development and the specific biology of the bearded dragon.

  17. Segregated phases in pulmonary surfactant membranes do not show coexistence of lipid populations with differentiated dynamic properties

    DEFF Research Database (Denmark)

    Bernardino de la Serna, Jorge; Orädd, Greger; Bagatolli, Luis

    2009-01-01

    The composition of pulmonary surfactant membranes and films has evolved to support a complex lateral structure, including segregation of ordered/disordered phases maintained up to physiological temperatures. In this study, we have analyzed the temperature-dependent dynamic properties of native...... surfactant membranes and membranes reconstituted from two surfactant hydrophobic fractions (i.e., all the lipids plus the hydrophobic proteins SP-B and SP-C, or only the total lipid fraction). These preparations show micrometer-sized fluid ordered/disordered phase coexistence, associated with a broad...... from the two types of surfactant hydrophobic extract. These latter results suggest that lipid dynamics are similar in the coexisting fluid phases observed by fluorescence microscopy. Additionally, it is found that surfactant proteins significantly reduce the average intramolecular lipid mobility...

  18. Plasma surfactant protein D levels and the relation to body mass index in a chinese population

    DEFF Research Database (Denmark)

    Zhao, X M; Wu, Y P; Wei, R

    2007-01-01

    Surfactant protein D (SP-D) is a member of the collectin family and is an important component of the pulmonary innate host defence. The protein has a widespread distribution in the human body and is present in multiple epithelia, in endothelium and in blood. Various studies have looked at the rel......Surfactant protein D (SP-D) is a member of the collectin family and is an important component of the pulmonary innate host defence. The protein has a widespread distribution in the human body and is present in multiple epithelia, in endothelium and in blood. Various studies have looked...

  19. Untapped therapeutic potential of surfactant proteins: is there a case for recombinant SP-D supplementation in neonatal lung disease?

    Science.gov (United States)

    Clark, Howard W

    2010-06-01

    Whilst pulmonary surfactant therapy has been highly successful in reducing mortality from respiratory distress syndrome of the newborn, a significant proportion of infants born at less than 28 weeks' gestation develop neonatal chronic lung disease. This has a complex pathogenesis but infection, inflammation, oxygen toxicity and ventilator-induced lung injury in the premature infant are all recognised risk factors for its development. Current surfactant therapies in clinical use do not contain all surfactant components and lack the hydrophilic surfactant proteins A and D. These proteins are known to have important roles in surfactant homeostasis and in protecting the lung against inflammation. This review examines the evidence from animal models supporting a role for surfactant protein-D in particular in reducing inflammation in the lung and speculates that supplementation of current surfactant therapies with recombinant forms of surfactant protein-D may help offset the risk of development of chronic lung disease.

  20. Delivery and performance of surfactant replacement therapies to treat pulmonary disorders.

    Science.gov (United States)

    El-Gendy, Nashwa; Kaviratna, Anubhav; Berkland, Cory; Dhar, Prajnaparamita

    2013-08-01

    Lung surfactant is crucial for optimal pulmonary function throughout life. An absence or deficiency of surfactant can affect the surfactant pool leading to respiratory distress. Even if the coupling between surfactant dysfunction and the underlying disease is not always well understood, using exogenous surfactants as replacement is usually a standard therapeutic option in respiratory distress. Exogenous surfactants have been extensively studied in animal models and clinical trials. The present article provides an update on the evolution of surfactant therapy, types of surfactant treatment, and development of newer-generation surfactants. The differences in the performance between various surfactants are highlighted and advanced research that has been conducted so far in developing the optimal delivery of surfactant is discussed.

  1. Cationic versus anionic surfactant in tuning the structure and interaction of nanoparticle, protein, and surfactant complexes.

    Science.gov (United States)

    Mehan, Sumit; Aswal, Vinod K; Kohlbrecher, Joachim

    2014-08-26

    The structure and interaction in complexes of anionic Ludox HS40 silica nanoparticle, anionic bovine serum albumin (BSA) protein, and cationic dodecyl trimethylammonium bromide (DTAB) surfactant have been studied using small-angle neutron scattering (SANS). The results are compared with similar complexes having anionic sodium dodecyl sulfate (SDS) surfactant (Mehan, S; Chinchalikar, A. J.; Kumar, S.; Aswal, V. K.; Schweins, R. Langmuir 2013, 29, 11290). In both cases (DTAB and SDS), the structure in nanoparticle-protein-surfactant complexes is predominantly determined by the interactions of the individual two-component systems. The nanoparticle-surfactant (mediated through protein-surfactant complex) and protein-surfactant interactions for DTAB, but nanoparticle-protein (mediated through protein-surfactant complex) and protein-surfactant interactions for SDS, are found to be responsible for the resultant structure of nanoparticle-protein-surfactant complexes. Irrespective of the charge on the surfactant, the cooperative binding of surfactant with protein leads to micellelike clusters of surfactant formed along the unfolded protein chain. The adsorption of these protein-surfactant complexes for DTAB on oppositely charged nanoparticles gives rise to the protein-surfactant complex-mediated aggregation of nanoparticles (similar to that of DTAB surfactant). It is unlike that of depletion-induced aggregation of nanoparticles with nonadsorption of protein-surfactant complexes for SDS in similarly charged nanoparticle systems (similar to that of protein alone). The modifications in nanoparticle aggregation as well as unfolding of protein in these systems as compared to the corresponding two-component systems have also been examined by selectively contrast matching the constituents.

  2. Evaluation of therapeutic pulmonary surfactants by thin liquid film methods.

    Science.gov (United States)

    Todorov, Roumen; Exerowa, Dotchi; Platikanov, Dimo; Bianco, Federico; Razzetti, Roberta

    2015-08-01

    An example of the application of the Black Foam Film (BFF) Method and the Wetting Film Method, using the Microinterferomertric and the Pressure Balance Techniques, for characterization interfacial properties of the animal derived therapeutic pulmonary surfactant preparations (TSP), is presented. BFF thickness, probability of black film formation, and disjoining pressure for foam films from TSP aqueous solutions are measured as well as the wetting properties of TSP solutions on solid surfaces with different hydrophobicity have been studied. Interfacial characteristics such as minimal surfactant concentration to obtain black film (critical concentration) and concentration at which a black film is 100% obtained (threshold concentration) are determined. An evaluation of the four widely used TSP – Curosurf, Infasurf, Survanta, and Alveofact – by these methods has been carried out. Thus the methods of the thin liquid films are useful tools for studying the interfacial properties of TSP solutions, as well as for their improvement.

  3. Molecular dynamics of surfactant protein C

    DEFF Research Database (Denmark)

    Ramírez, Eunice; Santana, Alberto; Cruz, Anthony

    2006-01-01

    Surfactant protein C (SP-C) is a membrane-associated protein essential for normal respiration. It has been found that the alpha-helix form of SP-C can undergo, under certain conditions, a transformation from an alpha-helix to a beta-strand conformation that closely resembles amyloid fibrils, which...

  4. Orphan G Protein–Coupled Receptor GPR116 Regulates Pulmonary Surfactant Pool Size

    OpenAIRE

    Bridges, James P.; Ludwig, Marie-Gabrielle; Mueller, Matthias; Kinzel, Bernd; Sato, Atsuyasu; Xu, Yan; Whitsett, Jeffrey A.; Ikegami, Machiko

    2013-01-01

    Pulmonary surfactant levels within the alveoli are tightly regulated to maintain lung volumes and promote efficient gas exchange across the air/blood barrier. Quantitative and qualitative abnormalities in surfactant are associated with severe lung diseases in children and adults. Although the cellular and molecular mechanisms that control surfactant metabolism have been studied intensively, the critical molecular pathways that sense and regulate endogenous surfactant levels within the alveolu...

  5. Understanding the mutual impact of interaction between hydrophobic nanoparticles and pulmonary surfactant monolayer.

    Science.gov (United States)

    Sachan, Amit K; Galla, Hans-Joachim

    2014-03-26

    Interaction between hydrophobic nanoparticles (NPs) and a pulmonary surfactant (PS) film leads to a shift in molecular packing of surfactant molecules in the PS film around the interacting NPs. The resultant structural arrangement of surfactants around the NPs may be a potential structural factor responsible for their high retention ability within the film. Moreover, during this interaction, surfactant molecules coat the NPs and change their surface properties.

  6. Jaagsiekte sheep retrovirus proviral clone JSRV(JS7), derived from the JS7 lung tumor cell line, induces ovine pulmonary carcinoma and is integrated into the surfactant protein A gene.

    Science.gov (United States)

    DeMartini, J C; Bishop, J V; Allen, T E; Jassim, F A; Sharp, J M; de las Heras, M; Voelker, D R; Carlson, J O

    2001-05-01

    Ovine pulmonary carcinoma (OPC) is a contagious neoplasm of alveolar epithelial type II (ATII) or Clara cells caused by a type D/B chimeric retrovirus, jaagsiekte sheep retrovirus (JSRV). Here we report the isolation, sequencing, pathogenicity, and integration site of a JSRV provirus isolated from a sheep lung tumor cell line (JS7). The sequence of the virus was 93 to 99% identical to other JSRV isolates and contained all of the expected open reading frames. To produce virions and test its infectivity, the JS7 provirus (JSRV(JS7)) was cloned into a plasmid containing a cytomegalovirus promoter and transfected into 293T cells. After intratracheal inoculation with virions from concentrated supernatant fluid, JSRV-associated OPC lesions were found in one of four lambs, confirming that JSRV(JS7) is pathogenic. In JS7-cell DNA, the viral genome was inserted in the protein-coding region for the surfactant protein A (SP-A) gene, which is highly expressed in ATII cells, in an orientation opposite to the direction of transcription of the SP-A gene. No significant transcription was detected from either the viral or the SP-A gene promoter in the JS7 cell line at passage level 170. The oncogenic significance of the JSRV proviral insertion involving the SP-A locus in the JS7 tumor cell line is unknown.

  7. Porcine lung surfactant protein B gene (SFTPB)

    DEFF Research Database (Denmark)

    Cirera Salicio, Susanna; Fredholm, Merete

    2008-01-01

    The porcine surfactant protein B (SFTPB) is a single copy gene on chromosome 3. Three different cDNAs for the SFTPB have been isolated and sequenced. Nucleotide sequence comparison revealed six nonsynonymous single nucleotide polymorphisms (SNPs), four synonymous SNPs and an in-frame deletion of 69...

  8. Regulation of pulmonary surfactant synthesis in fetal rat type II alveolar epithelial cells by microRNA-26a.

    Science.gov (United States)

    Zhang, Xiao-Qun; Zhang, Pan; Yang, Yang; Qiu, Jie; Kan, Qin; Liang, Hong-Lu; Zhou, Xiao-Yu; Zhou, Xiao-Guang

    2014-09-01

    Pulmonary surfactant, a unique developmentally regulated, phospholipid-rich lipoprotein, is synthesized by the type II epithelial cells (AECII) of the pulmonary alveolus, where it is stored in organelles termed lamellar bodies. The synthesis of pulmonary surfactant is under multifactorial control and is regulated by a number of hormones and factors, including glucocorticoids, prolactin, insulin, growth factors, estrogens, androgens, thyroid hormones, and catecholamines acting through beta-adrenergic receptors, and cAMP. While there is increasing evidence that microRNAs (miRNAs) are involved in the regulation of almost every cellular and physiological process, the potential role of miRNAs in the regulation of pulmonary surfactant synthesis remains unknown. miRNA-26a (miR-26a) has been predicted to target SMAD1, one of the bone morphogenetic protein (BMP) receptor downstream signaling proteins that plays a key role in differentiation of lung epithelial cells during lung development. In this study, we explored the regulation role of miR-26a in the synthesis of pulmonary surfactant. An adenoviral miR-26a overexpression vector was constructed and introduced into primary cultured fetal AECII. GFP fluorescence was observed to determinate the transfection efficiency and miR-26a levels were measured by RT-PCR. MTT was performed to analyze AECII viability. qRT-PCR and Western blotting were used to determine the mRNA and protein level of SMAD1 and surfactant-associated proteins. The results showed that miR-26a in fetal AECII was overexpressed after the transfection, and that the overexpression of miR-26a inhibited pulmonary surfactant synthesis in AECII. There was no significant change in cell proliferation. Our results further showed that overexpression of miR-26a reduced the SMAD1 expression both in mRNA and protein level in fetal AECII. These findings indicate that miR-26a regulates surfactant synthesis in fetal AECII through SMAD1.

  9. Interaction of the C-terminal peptide of pulmonary surfactant protein B (SP-B with a bicellar lipid mixture containing anionic lipid.

    Directory of Open Access Journals (Sweden)

    Alexander Sylvester

    Full Text Available The hydrophobic lung surfactant SP-B is essential for respiration. SP-B promotes spreading and adsorption of surfactant at the alveolar air-water interface and may facilitate connections between the surface layer and underlying lamellar reservoirs of surfactant material. SP-B63-78 is a cationic and amphipathic helical peptide containing the C-terminal helix of SP-B. (2H NMR has been used to examine the effect of SP-B63-78 on the phase behavior and dynamics of bicellar lipid dispersions containing the longer chain phospholipids DMPC-d 54 and DMPG and the shorter chain lipid DHPC mixed with a 3∶1∶1 molar ratio. Below the gel-to-liquid crystal phase transition temperature of the longer chain components, bicellar mixtures form small, rapidly reorienting disk-like particles with shorter chain lipid components predominantly found around the highly curved particle edges. With increasing temperature, the particles coalesce into larger magnetically-oriented structures and then into more extended lamellar phases. The susceptibility of bicellar particles to coalescence and large scale reorganization makes them an interesting platform in which to study peptide-induced interactions between lipid assemblies. SP-B63-78 is found to lower the temperature at which the orientable phase transforms to the more extended lamellar phase. The peptide also changes the spectrum of motions contributing to quadrupole echo decay in the lamellar phase. The way in which the peptide alters interactions between bilayered micelle structures may provide some insight into some aspects of the role of full-length SP-B in maintaining a functional surfactant layer in lungs.

  10. Interaction of the C-terminal peptide of pulmonary surfactant protein B (SP-B) with a bicellar lipid mixture containing anionic lipid.

    Science.gov (United States)

    Sylvester, Alexander; MacEachern, Lauren; Booth, Valerie; Morrow, Michael R

    2013-01-01

    The hydrophobic lung surfactant SP-B is essential for respiration. SP-B promotes spreading and adsorption of surfactant at the alveolar air-water interface and may facilitate connections between the surface layer and underlying lamellar reservoirs of surfactant material. SP-B63-78 is a cationic and amphipathic helical peptide containing the C-terminal helix of SP-B. (2)H NMR has been used to examine the effect of SP-B63-78 on the phase behavior and dynamics of bicellar lipid dispersions containing the longer chain phospholipids DMPC-d 54 and DMPG and the shorter chain lipid DHPC mixed with a 3∶1∶1 molar ratio. Below the gel-to-liquid crystal phase transition temperature of the longer chain components, bicellar mixtures form small, rapidly reorienting disk-like particles with shorter chain lipid components predominantly found around the highly curved particle edges. With increasing temperature, the particles coalesce into larger magnetically-oriented structures and then into more extended lamellar phases. The susceptibility of bicellar particles to coalescence and large scale reorganization makes them an interesting platform in which to study peptide-induced interactions between lipid assemblies. SP-B63-78 is found to lower the temperature at which the orientable phase transforms to the more extended lamellar phase. The peptide also changes the spectrum of motions contributing to quadrupole echo decay in the lamellar phase. The way in which the peptide alters interactions between bilayered micelle structures may provide some insight into some aspects of the role of full-length SP-B in maintaining a functional surfactant layer in lungs.

  11. Investigation of surfactant protein-D and interleukin-6 levels in patients with blunt chest trauma with multiple rib fractures and pulmonary contusions: a cross-sectional study in Black Sea Region of Turkey

    Science.gov (United States)

    Kurt, Aysel; Turut, Hasan; Acipayam, Ahmet; Kirbas, Aynur; Yuce, Suleyman; Cumhur Cure, Medine; Cure, Erkan

    2016-01-01

    Objective Multiple rib fractures (RFs) and pulmonary contusions (PCs), with resulting systemic lung inflammation, are the most common injuries caused by blunt chest trauma (BCT) in motor vehicle accidents. This study examined levels of the inflammation marker interleukin (IL)-6 and those of the acute-phase reactant surfactant protein (SP)-D in patients with BCT. Design Prospective, cross-sectional, observational study. Setting Single-centre, tertiary care hospital in the Black Sea Region of Turkey. Participants The study included 60 patients with BCT who were hospitalised in our thoracic surgery department. Parameters measures The SP-D and IL-6 serum levels of patients with RFs (two or more RFs) (n=30) and patients with PCs (n=30) were measured after 6 hours, 24 hours and 7 days, and compared with those of age-matched and gender-matched healthy participants. Results The 6-hour serum SP-D levels of the RFs (p=0.017) and PCs (plung injury. The levels of the systemic inflammation marker IL-6 and those of the acute-phase reactant SP-D were elevated in the present study. The SP-D level may be used as a marker in the follow-up of BCT-related complications. PMID:27733410

  12. Hybrid pulmonary surfactant-coated nanogels mediate efficient in vivo delivery of siRNA to murine alveolar macrophages.

    Science.gov (United States)

    De Backer, Lynn; Naessens, Thomas; De Koker, Stefaan; Zagato, Elisa; Demeester, Jo; Grooten, Johan; De Smedt, Stefaan C; Raemdonck, Koen

    2015-11-10

    The local delivery of small interfering RNA (siRNA) to the lungs may provide a therapeutic solution to a range of pulmonary disorders. Resident alveolar macrophages (rAM) in the bronchoalveolar lumen play a critical role in lung inflammatory responses and therefore constitute a particularly attractive target for siRNA therapeutics. However, achieving efficient gene silencing in the lung while avoiding pulmonary toxicity requires appropriate formulation of siRNA in functional nanocarriers. In this study, we evaluated pulmonary surfactant-coated dextran nanogels for the delivery of siRNA to rAM upon pharyngeal aspiration in BALB/c mice. Both the surfactant-coated and uncoated nanogels achieved high levels of siRNA uptake in rAM, yet only the surfactant-coated formulation could significantly reduce gene expression on the protein level. Surfactant-coated nanogels induced a profound downregulation of target mRNA levels, reaching 70% knockdown with ~1mgkg(-1) siRNA dose. In addition, only mild acute pro-inflammatory cytokine and chemokine responses were detected one day after nanoparticle aspiration, accompanied by a moderate neutrophil infiltration in the bronchoalveolar lumen. The latter could be substantially reduced by removal of excess surfactant from the formulation. Overall, our hybrid core-shell nanoparticles have demonstrated safe and effective siRNA delivery to rAM, providing a new therapeutic approach for treatment of inflammatory pathologies in the lung.

  13. Control study of pulmonary surfactant combined with CPAP and BIPAP ventilation modes respectively in treatment of neonatal NRDS

    Institute of Scientific and Technical Information of China (English)

    Yao Liu

    2016-01-01

    Objective:To analyze the differences in effect of pulmonary surfactant combined with CPAP and BIPAP ventilation modes respectively in treatment of neonatal NRDS.Methods:A total of 50 cases of children with neonatal respiratory distress syndrome (NRDS) born and receiving treatment in our hospital from August 2012 to January 2015 were selected as research subjects and randomly divided into observation group and control group, each with 25 cases. Control group received pulmonary surfactant combined with CPAP ventilation mode treatment, observation group received pulmonary surfactant combined with BIPAP ventilation mode treatment, and then differences in blood gas indicators and mechanical ventilation parameters, pulmonary artery pressure, endothelin and nitric oxide levels, blood coagulation and anticoagulation indicators and protein expression levels of CD24, TNF-α, IL-6 and IL-17A of two groups after treatment were compared.Results:PaO2, PH value and oxygenation index of observation group after treatment were higher than those of control group, and PaCO2, positive end-expiratory pressure, peak inspiratory pressure and inspired oxygen concentration were lower than those of control group; pulmonary artery pressure and EF-1 level of observation group after treatment were lower than those of control group, and NO level was higher than that of control group; PC, TPS and AT-Ⅲ levels of observation group after treatment were higher than those of control group, and D-D and vWF levels were lower than those of control group; protein expression of CD24 and IL-6 of observation group after treatment were lower than those of control group, and protein expression of TNF-α and IL-17A were higher than those of control group.Conclusion:Pulmonary surfactant combined with BIPAP ventilation mode treatment of children with NRDS can effectively optimize ventilation function and realize homeostasis, and it has active clinical significance.

  14. Lung remodeling in aging surfactant protein D deficient mice.

    Science.gov (United States)

    Schneider, Jan Philipp; Arkenau, Martina; Knudsen, Lars; Wedekind, Dirk; Ochs, Matthias

    2017-02-07

    Pulmonary surfactant, a mixture of lipids and proteins at the air-liquid interface of alveoli, prevents the lungs from collapsing due to surface tension. One constituent is surfactant-associated protein-D (SP-D), a protein involved in surfactant homeostasis and innate immunity. Mice deficient in SP-D (SP-D (-/-)) has been described as developing a characteristic phenotype which affects the surfactant system (including changes in the intra-cellular and intra-alveolar surfactant pool, alveolar epithelial type II cells and alveolar macrophages), lung architecture and its inflammatory state (development of an emphysema-like pathology, inflammatory cell infiltration). Furthermore, it has been described that these mice develop sub-pleural fibrosis and a thickening of alveolar septal walls. The aim of the present study was to systematically investigate the long term progression of this phenotype with special focus on parenchymal remodeling, whether there are progressive emphysematous changes and whether there is progressive septal wall thickening which might indicate the development of pulmonary fibrosis. By means of design-based stereology and light microscopy, lungs of wild type (wt) and SP-D (-/-) mice of four age groups (3, 6, 12 and ∼18 months) were investigated. The data do not suggest a relevant spontaneous pro-fibrotic remodeling or a destructive process in the aging SP-D (-/-) mice. We demonstrated neither a significant destructive emphysema nor significant thickening of alveolar septal walls, but the data suggest an increase in the number weighted mean alveolar volume in aging SP-D (-/-) mice without loss of alveoli or alveolar epithelial surface area per lung. This increase may reflect over-distension due to altered mechanical properties of alveoli. In the light of our findings and data from the literature, the question arises as to whether a lack of SP-D promotes structural changes in the lung which have been described as being associated with aging lungs

  15. Comparison of DPPC and DPPG environments in pulmonary surfactant models.

    Science.gov (United States)

    Morrow, Michael R; Temple, Sara; Stewart, June; Keough, Kevin M W

    2007-07-01

    Deuterium nuclear magnetic resonance was used to monitor lipid acyl-chain orientational order in suspensions of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) containing Ca(2+) and the lung surfactant proteins SP-A and SP-B separately and together. To distinguish between protein-lipid interactions involving the PC and PG lipid headgroups and to examine whether such interactions might influence spatial distribution of lipids within the bilayer, acyl chains on either the DPPC or the DPPG component of the mixture were deuterated. The lipid components of the resulting mixtures were thus either DPPC-d(62)/DPPG (7:3) or DPPC/DPPG-d(62) (7:3), respectively. SP-A had little effect on DPPC-d(62) chain order but did narrow the temperature range over which DPPG-d(62) ordered at the liquid-crystal-to-gel transition. No segregation of lipid components was seen for temperatures above or below the transition. Near the transition, though, there was evidence that SP-A promoted preferential depletion of DPPG from liquid crystalline domains in the temperature range over which gel and liquid crystal domains coexist. SP-B lowered average chain order of both lipids both above and below the main transition. The perturbations of chain order by SP-A and SP-B together were smaller than by SP-B alone. This reduction in perturbation of the lipids by the additional presence of SP-A likely indicated a strong interaction between SP-A and SP-B. The competitive lipid-lipid, lipid-protein, and protein-protein interactions suggested by these observations presumably facilitate the reorganization of surfactant material inherent in the transformation from lamellar bodies to a functional surfactant layer.

  16. Physicochemical properties of nanoparticles regulate translocation across pulmonary surfactant monolayer and formation of lipoprotein corona.

    Science.gov (United States)

    Hu, Guoqing; Jiao, Bao; Shi, Xinghua; Valle, Russell P; Fan, Qihui; Zuo, Yi Y

    2013-12-23

    Interaction with the pulmonary surfactant film, being the first line of host defense, represents the initial bio-nano interaction in the lungs. Such interaction determines the fate of the inhaled nanoparticles and their potential therapeutic or toxicological effect. Despite considerable progress in optimizing physicochemical properties of nanoparticles for improved delivery and targeting, the mechanisms by which inhaled nanoparticles interact with the pulmonary surfactant film are still largely unknown. Here, using combined in vitro and in silico methods, we show how hydrophobicity and surface charge of nanoparticles differentially regulate the translocation and interaction with the pulmonary surfactant film. While hydrophilic nanoparticles generally translocate quickly across the pulmonary surfactant film, a significant portion of hydrophobic nanoparticles are trapped by the surfactant film and encapsulated in lipid protrusions upon film compression. Our results support a novel model of pulmonary surfactant lipoprotein corona associated with inhaled nanoparticles of different physicochemical properties. Our data suggest that the study of pulmonary nanotoxicology and nanoparticle-based pulmonary drug delivery should consider this lipoprotein corona.

  17. No effect of ablation of surfactant protein-D on acute cerebral infarction in mice

    DEFF Research Database (Denmark)

    Lambertsen, Kate Lykke; Østergaard, Kamilla; Clausen, Bettina Hjelm

    2014-01-01

    BACKGROUND: Crosstalk between the immune system in the brain and the periphery may contribute to the long-term outcome both in experimental and clinical stroke. Although, the immune defense collectin surfactant protein-D (SP-D) is best known for its role in pulmonary innate immunity, SP-D is also...

  18. Biophysical influence of airborne carbon nanomaterials on natural pulmonary surfactant.

    Science.gov (United States)

    Valle, Russell P; Wu, Tony; Zuo, Yi Y

    2015-05-26

    Inhalation of nanoparticles (NP), including lightweight airborne carbonaceous nanomaterials (CNM), poses a direct and systemic health threat to those who handle them. Inhaled NP penetrate deep pulmonary structures in which they first interact with the pulmonary surfactant (PS) lining at the alveolar air-water interface. In spite of many research efforts, there is a gap of knowledge between in vitro biophysical study and in vivo inhalation toxicology since all existing biophysical models handle NP-PS interactions in the liquid phase. This technical limitation, inherent in current in vitro methodologies, makes it impossible to simulate how airborne NP deposit at the PS film and interact with it. Existing in vitro NP-PS studies using liquid-suspended particles have been shown to artificially inflate the no-observed adverse effect level of NP exposure when compared to in vivo inhalation studies and international occupational exposure limits (OELs). Here, we developed an in vitro methodology called the constrained drop surfactometer (CDS) to quantitatively study PS inhibition by airborne CNM. We show that airborne multiwalled carbon nanotubes and graphene nanoplatelets induce a concentration-dependent PS inhibition under physiologically relevant conditions. The CNM aerosol concentrations controlled in the CDS are comparable to those defined in international OELs. Development of the CDS has the potential to advance our understanding of how submicron airborne nanomaterials affect the PS lining of the lung.

  19. The Mycobacterium tuberculosis cell-surface glycoprotein apa as a potential adhesin to colonize target cells via the innate immune system pulmonary C-type lectin surfactant protein A.

    Science.gov (United States)

    Ragas, Aude; Roussel, Lucie; Puzo, Germain; Rivière, Michel

    2007-02-23

    Tuberculosis is still a major health problem, and understanding the mechanism by which Mycobacterium tuberculosis (Mtb) invades and colonizes its host target cells remains an important issue for the control of infection. The innate immune system C-type lectins (C-TLs), including the human pulmonary surfactant protein A (PSP-A), have been recently identified as determinant players in the early recognition of the invading pathogen and in mounting the host defense response. Although the antigenic lipoglycan mannosylated lipoarabinomannan is currently considered to be the major C-TL target on the mycobacterial surface, the recognition by some C-TLs of the only mycobacterial species composing the "Mtb complex" indicates that mannosylated lipoarabinomannan cannot account alone for this specificity. Thus, we searched for the mycobacterial molecules targeted by human PSP-A, focusing our attention on the Mtb surface glycoproteins. We developed an original functional proteomic approach based on a lectin blot assay using crude human bronchoalveolar lavage fluid as a source of physiological PSP-A. Combined with selective cell-surface protein extraction and mass spectrometry peptide mapping, this strategy allowed us to identify the Apa (alanine- and proline-rich antigenic) glycoprotein as new potential target for PSP-A. This result was supported by direct binding of PSP-A to purified Apa. Moreover, EDTA addition or deglycosylation of purified Apa samples completely abolished the interaction, demonstrating that the interaction is calcium- and mannose-dependent, as expected. Finally, we provide convincing evidence that Apa, formerly considered as mainly secreted, is associated with the cell wall for a sufficiently long time to aid in the attachment of PSP-A. Because, to date, Apa seems to be restricted to the Mtb complex strains, we propose that it may account for the selective recognition of those strains by PSP-A and other immune system C-TLs containing homologous functional

  20. Structural study of surfactant-dependent interaction with protein

    Energy Technology Data Exchange (ETDEWEB)

    Mehan, Sumit; Aswal, Vinod K., E-mail: vkaswal@barc.gov.in [Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Kohlbrecher, Joachim [Laboratory for Neutron Scattering, Paul Scherrer Institut, CH-5232 PSI Villigen (Switzerland)

    2015-06-24

    Small-angle neutron scattering (SANS) has been used to study the complex structure of anionic BSA protein with three different (cationic DTAB, anionic SDS and non-ionic C12E10) surfactants. These systems form very different surfactant-dependent complexes. We show that the structure of protein-surfactant complex is initiated by the site-specific electrostatic interaction between the components, followed by the hydrophobic interaction at high surfactant concentrations. It is also found that hydrophobic interaction is preferred over the electrostatic interaction in deciding the resultant structure of protein-surfactant complexes.

  1. Different effects of surfactant proteins B and C - implications for development of synthetic surfactants.

    Science.gov (United States)

    Curstedt, Tore; Johansson, Jan

    2010-06-01

    Treatment of premature newborn rabbits with synthetic surfactants containing a surfactant protein C analogue in a simple phospholipid mixture gives similar tidal volumes as treatment with poractant alfa (Curosurf(R)) but ventilation with a positive end-expiratory pressure (PEEP) is needed for this synthetic surfactant to stabilize the alveoli at end-expiration. The effect on lung gas volumes seems to depend on the structure of the peptide since treatment with a synthetic surfactant containing the 21-residue peptide (LysLeu(4))(4)Lys (KL(4)) gives low lung gas volumes in experiments also performed with PEEP. Surfactant preparations containing both surfactant proteins B and C or their analogues prevent alveolar collapse at end-expiration even if ventilated without PEEP. Treatment of premature newborn rabbits with different natural surfactants indicates that both the lipid composition and the proteins are important in order to stabilize the alveoli at end-expiration. Synthetic surfactants containing two peptides may be able to replace natural surfactants within the near future but more trials need to be performed before any conclusion can be drawn about the ideal composition of this new generation of synthetic surfactants.

  2. Artificial pulmonary surfactant as a carrier for intratracheally instilled insulin

    Institute of Scientific and Technical Information of China (English)

    Ying JI; Chen LIU; Yuan-ying PEI

    2007-01-01

    Aim: The relative bioavailabilities and effects on lung injury alleviation of 4 insu-lin-artificial pulmonary surfactant (INS-APS) preparations were studied in normal rats. The relationship between the minimal surface tension (γmin) of INS-APS and the absorption of insulin was also investigated. Methods: Four formulations of APS [1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/lecithin/palmitic acid (PA), DPPC/1-hexadecanol (Hex)/tyloxapol (Tyl), DPPC/L-α-phosphatidyl-DL-glyc-erol sodium salt (PG), DPPC/Tyl] were prepared by thin-film sonication method and direct sonication. The γmin of 4 APS dispersions was examined with and without INS by pulsating with a bubble surface tensiometer. In vivo experiments were performed in which serum glucose change and the insulin level were mea-sured by an enzymatic glucose reagent kit and a radioimmunology assay kit after IT to rats. The reduction in lung injury by INS-APS following 7 d of consecutive administration was evaluated by the pulmonary edema index (the weight ratio of wet lung to dry lung) and histopathology examination. Results: The γmin of all APS dispersions were below 10 mN/m. There was no significant difference (P>0.05) between the γmin of APS and the corresponding INS-APS. In vivo experi-ments showed a significant glucose level decrease and insulin absorption increase (P0.05) between INS/DPPC/Tyl, INS/DPPC/PG, and the control group. The pulmonary edema indices and histopatho-logical observation indicated that INS-APS could alleviate lung injury. Conclusion:The most potent hypoglycemic effect and insulin absorption increase in this study were obtained with INS/DPPC/Tyl. According to the results, there was a linear correlation between the γmin and relative bioavailability of INS-APS, suggesting a possible effect of the γmin of carders on the in vivo absorption of insulin. APS,DPPC/Tyl, and DPPC/PG dispersions might be the most efficient insulin pulmo-nary delivery carders in achieving a lower

  3. The N-terminal segment of pulmonary surfactant lipopeptide SP-C has intrinsic propensity to interact with and perturb phospholipid bilayers

    DEFF Research Database (Denmark)

    Plasencia, Inés; Rivas, Luis; Keough, Kevin M W

    2004-01-01

    In the present study, 13-residue peptides with sequences corresponding to the native N-terminal segment of pulmonary SP-C (surfactant protein C) have been synthesized and their interaction with phospholipid bilayers characterized. The peptides are soluble in aqueous media but associate spontaneou......In the present study, 13-residue peptides with sequences corresponding to the native N-terminal segment of pulmonary SP-C (surfactant protein C) have been synthesized and their interaction with phospholipid bilayers characterized. The peptides are soluble in aqueous media but associate...

  4. Inactivation of pulmonary surfactant due to serum-inhibited adsorption and reversal by hydrophilic polymers: experimental

    DEFF Research Database (Denmark)

    Taeusch, H William; de la Serna, Jorge Bernardino; Perez-Gil, Jesus

    2005-01-01

    The rate of change of surface pressure, pi, in a Langmuir trough following the deposition of surfactant suspensions on subphases containing serum, with or without polymers, is used to model a likely cause of surfactant inactivation in vivo: inhibition of surfactant adsorption due to competitive...... adsorption of surface active serum proteins. Aqueous suspensions of native porcine surfactant, organic extracts of native surfactant, and the clinical surfactants Curosurf, Infasurf, and Survanta spread on buffered subphases increase the surface pressure, pi, to approximately 40 mN/m within 2 min....... The variation with concentration, temperature, and mode of spreading confirmed Brewster angle microscopy observations that subphase to surface adsorption of surfactant is the dominant form of surfactant transport to the interface. However (with the exception of native porcine surfactant), similar rapid...

  5. Surfactant nebulisation : lung function, surfactant distribution and pulmonary blood flow distribution in lung lavaged rabbits

    NARCIS (Netherlands)

    Dijk, Peter H.; Heikamp, A; Bambang Oetomo, Sidarto

    1997-01-01

    Objective: Surfactant nebulisation is a promising alternative to surfactant instillation in newborns with the respiratory distress syndrome. Although less surfactant is deposited in the lung, it improves gas exchange, probably due to a superior distribution. We hypothesize that a more uniform distri

  6. Surfactant nebulisation : lung function, surfactant distribution and pulmonary blood flow distribution in lung lavaged rabbits

    NARCIS (Netherlands)

    Dijk, Peter H.; Heikamp, A; Bambang Oetomo, Sidarto

    1997-01-01

    Objective: Surfactant nebulisation is a promising alternative to surfactant instillation in newborns with the respiratory distress syndrome. Although less surfactant is deposited in the lung, it improves gas exchange, probably due to a superior distribution. We hypothesize that a more uniform distri

  7. Proteins and protein/surfactant mixtures at interfaces in motion

    NARCIS (Netherlands)

    Boerboom, F.J.G.

    2000-01-01

    The research described in this thesis covers a number of aspects of the relation between surface properties and foaming properties of proteins, low molecular surfactants and mixtures thereof. This work is the result of a question of the industrial partners if it is possible to understand

  8. Improvement of pulmonary surfactant activity by introducing D-amino acids into highly hydrophobic amphiphilic α-peptide Hel 13-5.

    Science.gov (United States)

    Nakamura, Yoshihiro; Yukitake, Ko; Nakahara, Hiromichi; Lee, Sooyoung; Shibata, Osamu; Lee, Sannamu

    2014-08-01

    The high costs of artificial pulmonary surfactants, ranging in hundreds per kilogram of body weight, used for treating the respiratory distress syndrome (RDS) premature babies have limited their applications. We have extensively studied soy lecithins and higher alcohols as lipid alternatives to expensive phospholipids such as DPPC and PG. As a substitute for the proteins, we have synthesized the peptide Hel 13-5D3 by introducing D-amino acids into a highly lipid-soluble, basic amphiphilic peptide, Hel 13-5, composed of 18 amino acid residues. Analysis of the surfactant activities of lipid-amphiphilic artificial peptide mixtures using lung-irrigated rat models revealed that a mixture (Murosurf SLPD3) of dehydrogenated soy lecithin, fractionated soy lecithin, palmitic acid (PA), and peptide Hel 13-5D3 (40:40:17.5:2.5, by weight) superior pulmonary surfactant activity than a commercially available pulmonary surfactant (beractant, Surfacten®). Experiments using ovalbumin-sensitized model animals revealed that the lipid-amphiphilic artificial peptide mixtures provided significant control over an increase in the pulmonary resistance induced by premature allergy reaction and reduced the number of acidocytes and neutrophils in lung-irrigated solution. The newly developed low-cost pulmonary surfactant system may be used for treatment of a wide variety of respiratory diseases.

  9. Bio-inspired pulmonary surfactant-modified nanogels: A promising siRNA delivery system.

    Science.gov (United States)

    De Backer, Lynn; Braeckmans, Kevin; Stuart, Marc C A; Demeester, Jo; De Smedt, Stefaan C; Raemdonck, Koen

    2015-05-28

    Inhalation therapy with small interfering RNA (siRNA) is a promising approach in the treatment of pulmonary disorders. However, clinical translation is severely limited by the lack of suitable delivery platforms. In this study, we aim to address this limitation by designing a novel bioinspired hybrid nanoparticle with a core-shell nanoarchitecture, consisting of a siRNA-loaded dextran nanogel (siNG) core and a pulmonary surfactant (Curosurf®) outer shell. The decoration of siNGs with a surfactant shell enhances the colloidal stability and prevents siRNA release in the presence of competing polyanions, which are abundantly present in biofluids. Additionally, the impact of the surfactant shell on the biological efficacy of the siNGs is determined in lung cancer cells. The presence of the surfactants substantially reduces the cellular uptake of siNGs. Remarkably, the lowered intracellular dose does not impede the gene silencing effect, suggesting a crucial role of the pulmonary surfactant in the intracellular processing of the nanoparticles. In order to surmount the observed reduction in cellular dose, folate is incorporated as a targeting ligand in the pulmonary surfactant shell to incite receptor-mediated endocytosis. The latter substantially enhances both cellular uptake and gene silencing potential, achieving efficient knockdown at siRNA concentrations in the low nanomolar range.

  10. Long-chain acyl-CoA dehydrogenase deficiency as a cause of pulmonary surfactant dysfunction.

    Science.gov (United States)

    Goetzman, Eric S; Alcorn, John F; Bharathi, Sivakama S; Uppala, Radha; McHugh, Kevin J; Kosmider, Beata; Chen, Rimei; Zuo, Yi Y; Beck, Megan E; McKinney, Richard W; Skilling, Helen; Suhrie, Kristen R; Karunanidhi, Anuradha; Yeasted, Renita; Otsubo, Chikara; Ellis, Bryon; Tyurina, Yulia Y; Kagan, Valerian E; Mallampalli, Rama K; Vockley, Jerry

    2014-04-11

    Long-chain acyl-CoA dehydrogenase (LCAD) is a mitochondrial fatty acid oxidation enzyme whose expression in humans is low or absent in organs known to utilize fatty acids for energy such as heart, muscle, and liver. This study demonstrates localization of LCAD to human alveolar type II pneumocytes, which synthesize and secrete pulmonary surfactant. The physiological role of LCAD and the fatty acid oxidation pathway in lung was subsequently studied using LCAD knock-out mice. Lung fatty acid oxidation was reduced in LCAD(-/-) mice. LCAD(-/-) mice demonstrated reduced pulmonary compliance, but histological examination of lung tissue revealed no obvious signs of inflammation or pathology. The changes in lung mechanics were found to be due to pulmonary surfactant dysfunction. Large aggregate surfactant isolated from LCAD(-/-) mouse lavage fluid had significantly reduced phospholipid content as well as alterations in the acyl chain composition of phosphatidylcholine and phosphatidylglycerol. LCAD(-/-) surfactant demonstrated functional abnormalities when subjected to dynamic compression-expansion cycling on a constrained drop surfactometer. Serum albumin, which has been shown to degrade and inactivate pulmonary surfactant, was significantly increased in LCAD(-/-) lavage fluid, suggesting increased epithelial permeability. Finally, we identified two cases of sudden unexplained infant death where no lung LCAD antigen was detectable. Both infants were homozygous for an amino acid changing polymorphism (K333Q). These findings for the first time identify the fatty acid oxidation pathway and LCAD in particular as factors contributing to the pathophysiology of pulmonary disease.

  11. The effect of titanium dioxide nanoparticles on pulmonary surfactant function and ultrastructure

    Directory of Open Access Journals (Sweden)

    Braun Armin

    2009-09-01

    Full Text Available Abstract Background Pulmonary surfactant reduces surface tension and is present at the air-liquid interface in the alveoli where inhaled nanoparticles preferentially deposit. We investigated the effect of titanium dioxide (TiO2 nanosized particles (NSP and microsized particles (MSP on biophysical surfactant function after direct particle contact and after surface area cycling in vitro. In addition, TiO2 effects on surfactant ultrastructure were visualized. Methods A natural porcine surfactant preparation was incubated with increasing concentrations (50-500 μg/ml of TiO2 NSP or MSP, respectively. Biophysical surfactant function was measured in a pulsating bubble surfactometer before and after surface area cycling. Furthermore, surfactant ultrastructure was evaluated with a transmission electron microscope. Results TiO2 NSP, but not MSP, induced a surfactant dysfunction. For TiO2 NSP, adsorption surface tension (γads increased in a dose-dependent manner from 28.2 ± 2.3 mN/m to 33.2 ± 2.3 mN/m (p min slightly increased from 4.8 ± 0.5 mN/m up to 8.4 ± 1.3 mN/m (p 2 NSP concentrations. Presence of NSP during surface area cycling caused large and significant increases in both γads (63.6 ± 0.4 mN/m and γmin (21.1 ± 0.4 mN/m. Interestingly, TiO2 NSP induced aberrations in the surfactant ultrastructure. Lamellar body like structures were deformed and decreased in size. In addition, unilamellar vesicles were formed. Particle aggregates were found between single lamellae. Conclusion TiO2 nanosized particles can alter the structure and function of pulmonary surfactant. Particle size and surface area respectively play a critical role for the biophysical surfactant response in the lung.

  12. Key interactions of surfactants in therapeutic protein formulations: A review.

    Science.gov (United States)

    Khan, Tarik A; Mahler, Hanns-Christian; Kishore, Ravuri S K

    2015-11-01

    Proteins as amphiphilic, surface-active macromolecules, demonstrate substantial interfacial activity, which causes considerable impact on their multifarious applications. A commonly adapted measure to prevent interfacial damage to proteins is the use of nonionic surfactants. Particularly in biotherapeutic formulations, the use of nonionic surfactants is ubiquitous in order to prevent the impact of interfacial stress on drug product stability. The scope of this review is to convey the current understanding of interactions of nonionic surfactants with proteins both at the interface and in solution, with specific focus to their effects on biotherapeutic formulations.

  13. Human decidua-derived mesenchymal stem cells differentiate into functional alveolar type II-like cells that synthesize and secrete pulmonary surfactant complexes.

    Science.gov (United States)

    Cerrada, Alejandro; de la Torre, Paz; Grande, Jesús; Haller, Thomas; Flores, Ana I; Pérez-Gil, Jesús

    2014-01-01

    Lung alveolar type II (ATII) cells are specialized in the synthesis and secretion of pulmonary surfactant, a lipid-protein complex that reduces surface tension to minimize the work of breathing. Surfactant synthesis, assembly and secretion are closely regulated and its impairment is associated with severe respiratory disorders. At present, well-established ATII cell culture models are not available. In this work, Decidua-derived Mesenchymal Stem Cells (DMSCs) have been differentiated into Alveolar Type II- Like Cells (ATII-LCs), which display membranous cytoplasmic organelles resembling lamellar bodies, the organelles involved in surfactant storage and secretion by native ATII cells, and accumulate disaturated phospholipid species, a surfactant hallmark. Expression of characteristic ATII cells markers was demonstrated in ATII-LCs at gene and protein level. Mimicking the response of ATII cells to secretagogues, ATII-LCs were able to exocytose lipid-rich assemblies, which displayed highly surface active capabilities, including faster interfacial adsorption kinetics than standard native surfactant, even in the presence of inhibitory agents. ATII-LCs could constitute a highly useful ex vivo model for the study of surfactant biogenesis and the mechanisms involved in protein processing and lipid trafficking, as well as the packing and storage of surfactant complexes.

  14. Human decidua-derived mesenchymal stem cells differentiate into functional alveolar type II-like cells that synthesize and secrete pulmonary surfactant complexes.

    Directory of Open Access Journals (Sweden)

    Alejandro Cerrada

    Full Text Available Lung alveolar type II (ATII cells are specialized in the synthesis and secretion of pulmonary surfactant, a lipid-protein complex that reduces surface tension to minimize the work of breathing. Surfactant synthesis, assembly and secretion are closely regulated and its impairment is associated with severe respiratory disorders. At present, well-established ATII cell culture models are not available. In this work, Decidua-derived Mesenchymal Stem Cells (DMSCs have been differentiated into Alveolar Type II- Like Cells (ATII-LCs, which display membranous cytoplasmic organelles resembling lamellar bodies, the organelles involved in surfactant storage and secretion by native ATII cells, and accumulate disaturated phospholipid species, a surfactant hallmark. Expression of characteristic ATII cells markers was demonstrated in ATII-LCs at gene and protein level. Mimicking the response of ATII cells to secretagogues, ATII-LCs were able to exocytose lipid-rich assemblies, which displayed highly surface active capabilities, including faster interfacial adsorption kinetics than standard native surfactant, even in the presence of inhibitory agents. ATII-LCs could constitute a highly useful ex vivo model for the study of surfactant biogenesis and the mechanisms involved in protein processing and lipid trafficking, as well as the packing and storage of surfactant complexes.

  15. Pulmonary surfactant in the airway physiology: a direct relaxing effect on the smooth muscle.

    Science.gov (United States)

    Calkovska, A; Uhliarova, B; Joskova, M; Franova, S; Kolomaznik, M; Calkovsky, V; Smolarova, S

    2015-04-01

    Beside alveoli, surface active material plays an important role in the airway physiology. In the upper airways it primarily serves in local defense. Lower airway surfactant stabilizes peripheral airways, provides the transport and defense, has barrier and anti-edematous functions, and possesses direct relaxant effect on the smooth muscle. We tested in vitro the effect of two surfactant preparations Curosurf® and Alveofact® on the precontracted smooth muscle of intra- and extra-pulmonary airways. Relaxation was more pronounced for lung tissue strip containing bronchial smooth muscle as the primary site of surfactant effect. The study does not confirm the participation of ATP-dependent potassium channels and cAMP-regulated epithelial chloride channels known as CFTR chloride channels, or nitric oxide involvement in contractile response of smooth muscle to surfactant.By controlling wall thickness and airway diameter, pulmonary surfactant is an important component of airway physiology. Thus, surfactant dysfunction may be included in pathophysiology of asthma, COPD, or other diseases with bronchial obstruction.

  16. Prophylaxis of neonatal respiratory distress syndrome by intra-amniotic administration of pulmonary surfactant

    Institute of Scientific and Technical Information of China (English)

    张建平; 王英兰; 王蕴慧; 张睿; 陈环; 苏浩彬

    2004-01-01

    Background Neonatal respiratory distress syndrome (NRDS) is caused by a deficiency in pulmonary surfactant (PS) and is one of the main reasons of neonatal mortality. This study was conducted to evaluate the efficacy and safety of intra-amniotic administration of pulmonary surfactant for prophylaxis of NRDS.Methods Forty-five pregnant women who were due for preterm delivery and whose fetuses' lungs proved immature were divided into two groups. Fifteen women (study group) were administered one dose of pulmonary surfactant injected into the amniotic cavity and delivered within several hours. Nothing was injected into the amniotic cavity of 30 women of the control group. The proportion of neonatal asphyxia, NRDS, mortality and the time in hospital were analyzed to determine if there was any difference between the two groups. Results There was no significant difference between the two groups for neonatal asphyxia. Foam tests showed that higher proportion of neonates in the study group than in the control group (56.3% vs 13.3%, P<0.05) had lung maturity. A greater number of control neonates (11/30, 32.3%) had NRDS, compared with the neonates given PS via the amniotic cavity before delivery (1/16, 6.3%, P<0.05). The neonates in the study group spent nearly 10 days less in hospital than the control group [(32.4±7.6) days vs (42.0±15.7) days, P<0.05], but the difference in mortality between the two groups was not statistically significant. Conclusions Intra-amniotic administration of pulmonary surfactant can significantly reduce the proportion of NRDS and the time in hospital of preterm neonates. Whether this method can reduce the mortality of preterm neonates needs to be evaluated further. Intra-amniotic administration of pulmonary surfactant provides an additional effectual means for NRDS prophylaxis.

  17. The anatomy, physics, and physiology of gas exchange surfaces: is there a universal function for pulmonary surfactant in animal respiratory structures?

    Science.gov (United States)

    Orgeig, Sandra; Bernhard, Wolfgang; Biswas, Samares C; Daniels, Christopher B; Hall, Stephen B; Hetz, Stefan K; Lang, Carol J; Maina, John N; Panda, Amiya K; Perez-Gil, Jesus; Possmayer, Fred; Veldhuizen, Ruud A; Yan, Wenfei

    2007-10-01

    (Orgeig and Daniels) This surfactant symposium reflects the integrative and multidisciplinary aims of the 1st ICRB, by encompassing in vitro and in vivo research, studies of vertebrates and invertebrates, and research across multiple disciplines. We explore the physical and structural challenges that face gas exchange surfaces in vertebrates and insects, by focusing on the role of the surfactant system. Pulmonary surfactant is a complex mixture of lipids and proteins that lines the air-liquid interface of the lungs of all air-breathing vertebrates, where it functions to vary surface tension with changing lung volume. We begin with a discussion of the extraordinary conservation of the blood-gas barrier among vertebrate respiratory organs, which has evolved to be extremely thin, thereby maximizing gas exchange, but simultaneously strong enough to withstand significant distension forces. The principal components of pulmonary surfactant are highly conserved, with a mixed phospholipid and neutral lipid interfacial film that is established, maintained and dynamically regulated by surfactant proteins (SP). A wide variation in the concentrations of individual components exists, however, and highlights lipidomic as well as proteomic adaptations to different physiological needs. As SP-B deficiency in mammals is lethal, oxidative stress to SP-B is detrimental to the biophysical function of pulmonary surfactant and SP-B is evolutionarily conserved across the vertebrates. It is likely that SP-B was essential for the evolutionary origin of pulmonary surfactant. We discuss three specific issues of the surfactant system to illustrate the diversity of function in animal respiratory structures. (1) Temperature: In vitro analyses of the behavior of different model surfactant films under dynamic conditions of surface tension and temperature suggest that, contrary to previous beliefs, the alveolar film may not have to be substantially enriched in the disaturated phospholipid

  18. The interplay of lung surfactant proteins and lipids assimilates the macrophage clearance of nanoparticles.

    Directory of Open Access Journals (Sweden)

    Christian A Ruge

    Full Text Available The peripheral lungs are a potential entrance portal for nanoparticles into the human body due to their large surface area. The fact that nanoparticles can be deposited in the alveolar region of the lungs is of interest for pulmonary drug delivery strategies and is of equal importance for toxicological considerations. Therefore, a detailed understanding of nanoparticle interaction with the structures of this largest and most sensitive part of the lungs is important for both nanomedicine and nanotoxicology. Astonishingly, there is still little known about the bio-nano interactions that occur after nanoparticle deposition in the alveoli. In this study, we compared the effects of surfactant-associated protein A (SP-A and D (SP-D on the clearance of magnetite nanoparticles (mNP with either more hydrophilic (starch or hydrophobic (phosphatidylcholine surface modification by an alveolar macrophage (AM cell line (MH-S using flow cytometry and confocal microscopy. Both proteins enhanced the AM uptake of mNP compared with pristine nanoparticles; for the hydrophilic ST-mNP, this effect was strongest with SP-D, whereas for the hydrophobic PL-mNP it was most pronounced with SP-A. Using gel electrophoretic and dynamic light scattering methods, we were able to demonstrate that the observed cellular effects were related to protein adsorption and to protein-mediated interference with the colloidal stability. Next, we investigated the influence of various surfactant lipids on nanoparticle uptake by AM because lipids are the major surfactant component. Synthetic surfactant lipid and isolated native surfactant preparations significantly modulated the effects exerted by SP-A and SP-D, respectively, resulting in comparable levels of macrophage interaction for both hydrophilic and hydrophobic nanoparticles. Our findings suggest that because of the interplay of both surfactant lipids and proteins, the AM clearance of nanoparticles is essentially the same, regardless

  19. The interplay of lung surfactant proteins and lipids assimilates the macrophage clearance of nanoparticles.

    Science.gov (United States)

    Ruge, Christian A; Schaefer, Ulrich F; Herrmann, Jennifer; Kirch, Julian; Cañadas, Olga; Echaide, Mercedes; Pérez-Gil, Jesús; Casals, Cristina; Müller, Rolf; Lehr, Claus-Michael

    2012-01-01

    The peripheral lungs are a potential entrance portal for nanoparticles into the human body due to their large surface area. The fact that nanoparticles can be deposited in the alveolar region of the lungs is of interest for pulmonary drug delivery strategies and is of equal importance for toxicological considerations. Therefore, a detailed understanding of nanoparticle interaction with the structures of this largest and most sensitive part of the lungs is important for both nanomedicine and nanotoxicology. Astonishingly, there is still little known about the bio-nano interactions that occur after nanoparticle deposition in the alveoli. In this study, we compared the effects of surfactant-associated protein A (SP-A) and D (SP-D) on the clearance of magnetite nanoparticles (mNP) with either more hydrophilic (starch) or hydrophobic (phosphatidylcholine) surface modification by an alveolar macrophage (AM) cell line (MH-S) using flow cytometry and confocal microscopy. Both proteins enhanced the AM uptake of mNP compared with pristine nanoparticles; for the hydrophilic ST-mNP, this effect was strongest with SP-D, whereas for the hydrophobic PL-mNP it was most pronounced with SP-A. Using gel electrophoretic and dynamic light scattering methods, we were able to demonstrate that the observed cellular effects were related to protein adsorption and to protein-mediated interference with the colloidal stability. Next, we investigated the influence of various surfactant lipids on nanoparticle uptake by AM because lipids are the major surfactant component. Synthetic surfactant lipid and isolated native surfactant preparations significantly modulated the effects exerted by SP-A and SP-D, respectively, resulting in comparable levels of macrophage interaction for both hydrophilic and hydrophobic nanoparticles. Our findings suggest that because of the interplay of both surfactant lipids and proteins, the AM clearance of nanoparticles is essentially the same, regardless of different

  20. Pulmonary surfactant function studied with the pulsating bubble surfactometer (PBS) and the capillary surfactometer (CS).

    Science.gov (United States)

    Enhorning, G

    2001-05-01

    Two instruments, the pulsating bubble surfactometer (PBS) and the capillary surfactometer (CS), were constructed for a study of pulmonary surfactant's physical properties. The instruments study spherical surfaces as in alveoli (PBS) and cylindrical surfaces as in terminal conducting airways (CS). Phospholipids, pulmonary surfactant's main components, are amphiphilic and, therefore, spontaneously form a film at air-liquid interfaces. When the film in the PBS is compressed to a reduced area during 'expiration', the molecules come closer together. Thereby, a high surface pressure develops, causing surface tension to be reduced more than bubble radius. If these conditions, observed with the PBS are analogous in lungs, alveolar stability would be promoted. The CS was developed for a study of how surfactant has ability to maintain patency of narrow conducting airways. Provided adsorption is extremely fast, a surfactant film will line the terminal conducting airway as soon as liquid blocking the airway has been extruded. During expiration that film will develop high surface pressure (=low surface tension). This will counteract the tendency for liquid to accumulate in the airway's most narrow section. If surfactant is dysfunctioning, liquid is likely to accumulate and block terminal airways. Airway resistance would then increase, causing FEV(1) to be reduced.

  1. Orphan G Protein–Coupled Receptor GPR116 Regulates Pulmonary Surfactant Pool Size

    Science.gov (United States)

    Ludwig, Marie-Gabrielle; Mueller, Matthias; Kinzel, Bernd; Sato, Atsuyasu; Xu, Yan; Whitsett, Jeffrey A.; Ikegami, Machiko

    2013-01-01

    Pulmonary surfactant levels within the alveoli are tightly regulated to maintain lung volumes and promote efficient gas exchange across the air/blood barrier. Quantitative and qualitative abnormalities in surfactant are associated with severe lung diseases in children and adults. Although the cellular and molecular mechanisms that control surfactant metabolism have been studied intensively, the critical molecular pathways that sense and regulate endogenous surfactant levels within the alveolus have not been identified and constitute a fundamental knowledge gap in the field. In this study, we demonstrate that expression of an orphan G protein–coupled receptor, GPR116, in the murine lung is developmentally regulated, reaching maximal levels 1 day after birth, and is highly expressed on the apical surface of alveolar type I and type II epithelial cells. To define the physiological role of GPR116 in vivo, mice with a targeted mutation of the Gpr116 locus, Gpr116Δexon17, were generated. Gpr116Δexon17 mice developed a profound accumulation of alveolar surfactant phospholipids at 4 weeks of age (12-fold) that was further increased at 20 weeks of age (30-fold). Surfactant accumulation in Gpr116Δexon17 mice was associated with increased saturated phosphatidylcholine synthesis at 4 weeks and the presence of enlarged, lipid-laden macrophages, neutrophilia, and alveolar destruction at 20 weeks. mRNA microarray analyses indicated that P2RY2, a purinergic receptor known to mediate surfactant secretion, was induced in Gpr116Δexon17 type II cells. Collectively, these data support the concept that GPR116 functions as a molecular sensor of alveolar surfactant lipid pool sizes by regulating surfactant secretion. PMID:23590306

  2. Cell-specific modulation of surfactant proteins by ambroxol treatment.

    Science.gov (United States)

    Seifart, Carola; Clostermann, Ursula; Seifart, Ulf; Müller, Bernd; Vogelmeier, Claus; von Wichert, Peter; Fehrenbach, Heinz

    2005-02-15

    Ambroxol [trans-4-(2-amino-3,5-dibromobenzylamino)-cyclohexanole hydrochloride], a mucolytic agent, was postulated to provide surfactant stimulatory properties and was previously used to prevent surfactant deficiency. Currently, the underlying mechanisms are not exactly clear. Because surfactant homeostasis is regulated by surfactant-specific proteins (SP), we analyzed protein amount and mRNA expression in whole lung tissue, isolated type II pneumocytes and bronchoalveolar lavage of Sprague-Dawley rats treated with ambroxol i.p. (75 mg/kg body weight, twice a day [every 12 h]). The methods used included competitive polymerase chain reaction (RT-PCR), Northern blotting, Western immunoblotting, and immunohistochemistry. In isolated type II pneumocytes of ambroxol-treated animals, SP-C protein and mRNA content were increased, whereas SP-A, -B and -D protein, mRNA, and immunoreactivity remained unaffected. However, ambroxol treatment resulted in a significant increase of SP-B and in a decrease of SP-D in whole lung tissue with enhanced immunostaining for SP-B in Clara Cells. SP-A and SP-D were significantly decreased in BAL fluid of ambroxol-treated animals. The data suggest that surfactant protein expression is modulated in a cell-specific manner by ambroxol, as type II pneumocytes exhibited an increase in SP-C, whereas Clara cells exhibited an increase in the immunoreactivity for SP-B accounting for the increased SP-B content of whole lung tissue. The results indicate that ambroxol may exert its positive effects, observed in the treatment of diseases related to surfactant deficiency, via modulation of surfactant protein expression.

  3. Maintained inspiratory activity during proportional assist ventilation in surfactant-depleted cats early after surfactant instillation: phrenic nerve and pulmonary stretch receptor activity

    Directory of Open Access Journals (Sweden)

    Schaller Peter

    2006-03-01

    Full Text Available Abstract Background Inspiratory activity is a prerequisite for successful application of patient triggered ventilation such as proportional assist ventilation (PAV. It has recently been reported that surfactant instillation increases the activity of slowly adapting pulmonary stretch receptors (PSRs followed by a shorter inspiratory time (Sindelar et al, J Appl Physiol, 2005 [Epub ahead of print]. Changes in lung mechanics, as observed in preterm infants with respiratory distress syndrome and after surfactant treatment, might therefore influence the inspiratory activity when applying PAV early after surfactant treatment. Objective To investigate the regulation of breathing and ventilatory response in surfactant-depleted young cats during PAV and during continuous positive airway pressure (CPAP early after surfactant instillation in relation to phrenic nerve activity (PNA and the activity of PSRs. Methods Seven anesthetized, endotracheally intubated young cats were exposed to periods of CPAP and PAV with the same end-expiratory pressure (0.2–0.5 kPa before and after lung lavage and after surfactant instillation. PAV was set to compensate for 75% of the lung elastic recoil. Results Tidal volume and respiratory rate were higher with lower PaCO2 and higher PaO2 during PAV than during CPAP both before and after surfactant instillation (p Conclusion PSR activity and the control of breathing are maintained during PAV in surfactant-depleted cats early after surfactant instillation, with a higher ventilatory response and a lower breathing effort than during CPAP.

  4. Structural characterisation of human proteinosis surfactant protein A

    DEFF Research Database (Denmark)

    Leth-Larsen, Rikke; Holmskov, U; Højrup, P

    2000-01-01

    Human surfactant protein-A (SP-A) has been purified from a proteinosis patient and characterised by a combination of automated Edman degradation and mass spectrometry. The complete protein sequence was characterised. The major part of SP-A was shown to consist of SP-A2 gene product, and only...

  5. 9,10-Phenanthrenequinone promotes secretion of pulmonary aldo-keto reductases with surfactant.

    Science.gov (United States)

    Matsunaga, Toshiyuki; Haga, Mariko; Watanabe, Gou; Shinoda, Yuhki; Endo, Satoshi; Kajiwara, Yu; Tanaka, Hiroyuki; Inagaki, Naoki; El-Kabbani, Ossama; Hara, Akira

    2012-02-01

    9,10-Phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust particles, induces apoptosis via the generation of reactive oxygen species (ROS) because of 9,10-PQ redox cycling. We have found that intratracheal infusion of 9,10-PQ facilitates the secretion of surfactant into rat alveolus. In the cultured rat lung, treatment with 9,10-PQ results in an increase in a lower-density surfactant by ROS generation through redox cycling of the quinone. The surfactant contains aldo-keto reductase (AKR) 1C15, which reduces 9,10-PQ and the enzyme level in the surfactant increases on treatment with 9,10-PQ suggesting an involvement of AKR1C15 in the redox cycling of the quinone. In six human cell types (A549, MKN45, Caco2, Hela, Molt4 and U937) only type II epithelial A549 cells secrete three human AKR1C subfamily members (AKR1C1, AKR1C2 and AKR1C3) with the surfactant into the medium; this secretion is highly increased by 9,10-PQ treatment. Using in vitro enzyme inhibition analysis, we have identified AKR1C3 as the most abundantly secreted AKR1C member. The AKR1C enzymes in the medium efficiently reduce 9,10-PQ and initiate its redox cycling accompanied by ROS production. The exposure of A549 cells to 9,10-PQ provokes viability loss, which is significantly protected by the addition of the AKR1C3 inhibitor and antioxidant enzyme and by the removal of the surfactants from the culture medium. Thus, the AKR1C enzymes secreted in pulmonary surfactants probably participate in the toxic mechanism triggered by 9,10-PQ.

  6. [The role of individual stress resistance in realization of immobilization and zoosocial stress effects on pulmonary surfactant system].

    Science.gov (United States)

    Vasil'eva, N N; Bryndina, I G

    2012-07-01

    The aim of the present study was to investigate the effect of chronic exposure to immobilization and psychosocial stress on surface activity, biochemical composition of pulmonary surfactant and lung fluid balance of rats with different stress-resistance. It is shown that both types of stress lead to elevation of lysophospholipids level and decrease of surface-active properties of pulmonary surfactant, more prominent in stress-vulnerable rats. Blood supply was decreased and extravascular fluid was increased under the psychosocial stress only in stress-vulnerable animals, in all rest cases the blood supply was increased and the content of extravascular fluid was not changed. Surfactant alteration was coupled on the level of 11-OCS in the blood and amount of fluid in the lungs. The obtained results indicate that different degree of impairment in the pulmonary surfactant system during immobilization and psychosocial conflicts depends on different resistance to emotional stress.

  7. Design-based stereological analysis of the lung parenchymal architecture and alveolar type II cells in surfactant protein A and D double deficient mice

    DEFF Research Database (Denmark)

    Jung, A; Allen, L; Nyengaard, Jens Randel

    2005-01-01

    overlapping as well as distinct functions. The present study provides a design-based stereological analysis of adult mice deficient in both SP-A and SP-D (A(-)D(-)) with special emphasis on parameters characterizing alveolar architecture and surfactant-producing type II cells. Compared to wild-type, A......, but the mean volume of a single lamellar body remains constant. These results demonstrate that chronic deficiency of SP-A and SP-D in mice leads to parenchymal remodeling, type II cell hyperplasia and hypertrophy, and disturbed intracellular surfactant metabolism. The design-based stereological approach......Alveolar epithelial type II cells synthesize and secrete surfactant. The surfactant-associated proteins A and D (SP-A and SP-D), members of the collectin protein family, participate in pulmonary immune defense, modulation of inflammation, and surfactant metabolism. Both proteins are known to have...

  8. Interactions among pulmonary surfactant, vernix caseosa, and intestinal enterocytes: intra-amniotic administration of fluorescently liposomes to pregnant rabbits.

    Science.gov (United States)

    Nishijima, Koji; Shukunami, Ken-ichi; Yoshinari, Hideo; Takahashi, Jin; Maeda, Hideyuki; Takagi, Hitoshi; Kotsuji, Fumikazu

    2012-08-01

    Although vernix caseosa is known to be a natural biofilm at birth, human pulmonary surfactant commences to remove the vernix from fetal skin into the amniotic fluid at gestational week 34, i.e., well before delivery. To explain this paradox, we first produced two types of fluorescently labeled liposomes displaying morphology similar to that of pulmonary surfactant and vernix caseosa complexes. We then continuously administered these liposomes into the amniotic fluid space of pregnant rabbits. In addition, we produced pulmonary surfactant and vernix caseosa complexes and administered them into the amniotic fluid space of pregnant rabbits. The intra-amniotic infused fluorescently labeled liposomes were absorbed into the fetal intestinal epithelium. However, the liposomes were not transported to the livers of fetal rabbits. We also revealed that continuous administration of micelles derived from pulmonary surfactants and vernix caseosa protected the small intestine of the rabbit fetus from damage due to surgical intervention. Our results indicate that pulmonary surfactant and vernix caseosa complexes in swallowed amniotic fluid might locally influence fetal intestinal enterocytes. Although the present studies are primarily observational and further studies are needed, our findings elucidate the physiological interactions among pulmonary, dermal-epidermal, and gastrointestinal developmental processes.

  9. Proteomic and Lipidomic Analysis of Nanoparticle Corona upon Contact with Lung Surfactant Reveals Differences in Protein, but Not Lipid Composition.

    Science.gov (United States)

    Raesch, Simon Sebastian; Tenzer, Stefan; Storck, Wiebke; Rurainski, Alexander; Selzer, Dominik; Ruge, Christian Arnold; Perez-Gil, Jesus; Schaefer, Ulrich Friedrich; Lehr, Claus-Michael

    2015-12-22

    Pulmonary surfactant (PS) constitutes the first line of host defense in the deep lung. Because of its high content of phospholipids and surfactant specific proteins, the interaction of inhaled nanoparticles (NPs) with the pulmonary surfactant layer is likely to form a corona that is different to the one formed in plasma. Here we present a detailed lipidomic and proteomic analysis of NP corona formation using native porcine surfactant as a model. We analyzed the adsorbed biomolecules in the corona of three NP with different surface properties (PEG-, PLGA-, and Lipid-NP) after incubation with native porcine surfactant. Using label-free shotgun analysis for protein and LC-MS for lipid analysis, we quantitatively determined the corona composition. Our results show a conserved lipid composition in the coronas of all investigated NPs regardless of their surface properties, with only hydrophilic PEG-NPs adsorbing fewer lipids in total. In contrast, the analyzed NP displayed a marked difference in the protein corona, consisting of up to 417 different proteins. Among the proteins showing significant differences between the NP coronas, there was a striking prevalence of molecules with a notoriously high lipid and surface binding, such as, e.g., SP-A, SP-D, DMBT1. Our data indicate that the selective adsorption of proteins mediates the relatively similar lipid pattern in the coronas of different NPs. On the basis of our lipidomic and proteomic analysis, we provide a detailed set of quantitative data on the composition of the surfactant corona formed upon NP inhalation, which is unique and markedly different to the plasma corona.

  10. Circulating surfactant protein D is decreased in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Hoegh, Silje Vermedal; Voss, Anne; Sorensen, Grith Lykke

    2009-01-01

    Objective. Deficiencies of innate immune molecules like mannan binding lectin (MBL) have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Surfactant protein D (SP-D) and MBL belong to the same family of innate immune molecules - the collectins, which share important...

  11. Primary alveolar capillary dysplasia (acinar dysplasia) and surfactant protein B deficiency: a clinical, radiological and pathological study

    Energy Technology Data Exchange (ETDEWEB)

    Hugosson, Claes O.; Khoumais, Nuha [King Faisal Specialist Hospital and Research Centre, Department of Radiology MBC 28, Riyadh (Saudi Arabia); Salama, Husam M.; Kattan, Abdul H. [King Faisal Specialist Hospital and Research Centre, Department of Paediatrics, Riyadh (Saudi Arabia); Al-Dayel, Fouad [King Faisal Specialist Hospital and Research Centre, Department of Pathology, Riyadh (Saudi Arabia)

    2005-03-01

    Full-term infants with severe and prolonged respiratory distress represent a diagnostic challenge. Plain radiographic findings may be nonspecific or similar to classic surfactant deficiency disease for infants with surfactant protein B deficiency and acinar dysplasia. Objectives: To describe the similar clinical-radiolgical patterns of two rare neonatal conditions. Six newborn babies with severe respiratory distress at birth demonstrated clinical and radiographically prolonged and progressive diffuse pulmonary opacification. All infants demonstrated hyperinflation of the lungs. The diffuse hazy opacification, which varied from mild (n=3) to moderate (n=3), progressed to severe diffuse opacification preceding death, which occurred at 12-36 days of life. Open lung biopsy confirmed the diagnosis of primary alveolar acinar dysplasia (AD) in four infants and surfactant protein B deficiency (SPBD) in two infants. In full-term babies with unexplained progressive respiratory distress from birth and progress of radiological changes, both AD and SPBD should be considered. (orig.)

  12. Exogenous pulmonary surfactant prevents the development of intra-abdominal adhesions in rats.

    Science.gov (United States)

    Schanaider, Alberto; Cotta-Pereira, Ricardo; Silva, Paulo C; Macedo-Ramos, Hugo; Silva, Johnatas D; Teixeira, Pedro A C; Pannain, Vera L N; Rocco, Patricia R M; Baetas-da-Cruz, Wagner

    2016-04-01

    Intra-abdominal adhesions are major post-operative complications for which no effective means of prevention is available. We aimed to evaluate the efficacy of exogenous pulmonary surfactant administration in the prevention of post-operative abdominal adhesions. Rats were randomly assigned to undergo laparotomy (L) or gastroenterostomy (GE) and then treated with surfactant (groups L-S and GE-S, respectively). Intra-abdominal adhesions, collagen fibre content, metalloproteinase (MMP)-9, expression of growth factors (TGF-β, KGF and VEGF), type III procollagen (PCIII) and pro-caspase 3, as well as isolectin B4 and ED1-positive cells expressing MMP-9, were evaluated. Groups treated with surfactant (GE-S and L-S) exhibited fewer adhesions. A significant reduction in collagen fibre content was observed in GE-S compared to GE animals (P abdominal adhesions triggered by laparotomy and gastrointestinal anastomosis, thus preventing fibrosis formation at the peritoneal surfaces. This preclinical study suggests an innovative treatment strategy for intra-abdominal adhesions with surfactant and to endorse its putative mechanism of action.

  13. Exposure to polymers reverses inhibition of pulmonary surfactant by serum, meconium, or cholesterol in the captive bubble surfactometer.

    Science.gov (United States)

    López-Rodríguez, Elena; Ospina, Olga Lucía; Echaide, Mercedes; Taeusch, H William; Pérez-Gil, Jesús

    2012-10-03

    Dysfunction of pulmonary surfactant in the lungs is associated with respiratory pathologies such as acute respiratory distress syndrome or meconium aspiration syndrome. Serum, cholesterol, and meconium have been described as inhibitory agents of surfactant's interfacial activity once these substances appear in alveolar spaces during lung injury and inflammation. The deleterious action of these agents has been only partly evaluated under physiologically relevant conditions. We have optimized a protocol to assess surfactant inhibition by serum, cholesterol, or meconium in the captive bubble surfactometer. Specific measures of surface activity before and after native surfactant was exposed to inhibitors included i), film formation, ii), readsorption of material from surface-associated reservoirs, and iii), interfacial film dynamics during compression-expansion cycling. Results show that serum creates a steric barrier that impedes surfactant reaching the interface. A mechanical perturbation of this barrier allows native surfactant to compete efficiently with serum to form a highly surface-active film. Exposure of native surfactant to cholesterol or meconium, on the other hand, modifies the compressibility of surfactant films though optimal compressibility properties recover on repetitive compression-expansion cycling. Addition of polymers like dextran or hyaluronic acid to surfactant fully reverses inhibition by serum. These polymers also prevent surfactant inhibition by cholesterol or meconium, suggesting that the protective action of polymers goes beyond the mere enhancement of interfacial adsorption as described by depletion force theories.

  14. Charged particles interacting with a mixed supported lipid bilayer as a biomimetic pulmonary surfactant.

    Science.gov (United States)

    Munteanu, B; Harb, F; Rieu, J P; Berthier, Y; Tinland, B; Trunfio-Sfarghiu, A-M

    2014-08-01

    This study shows the interactions of charged particles with mixed supported lipid bilayers (SLB) as biomimetic pulmonary surfactants. We tested two types of charged particles: positively charged and negatively charged particles. Two parameters were measured: adsorption density of particles on the SLB and the diffusion coefficient of lipids by FRAPP techniques as a measure of interaction strength between particles and lipids. We found that positively charged particles do not adsorb on the bilayer, probably due to the electrostatic repulsion between positively charged parts of the lipid head and the positive groups on the particle surface, therefore no variation in diffusion coefficient of lipid molecules was observed. On the contrary, the negatively charged particles, driven by electrostatic interactions are adsorbed onto the supported bilayer. The adsorption of negatively charged particles increases with the zeta-potential of the particle. Consecutively, the diffusion coefficient of lipids is reduced probably due to binding onto the lipid heads which slows down their Brownian motion. The results are directly relevant for understanding the interactions of particulate matter with pulmonary structures which could lead to pulmonary surfactant inhibition or deficiency causing severe respiratory distress or pathologies.

  15. Two novel mutations in surfactant protein-C, lung function and obstructive lung disease

    DEFF Research Database (Denmark)

    Baekvad-Hansen, Marie; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne

    2010-01-01

    Dominant mutations in the surfactant protein-C(SFTPC) gene have been linked with interstitial lung disease. The frequency of lung disease due to SFTPC mutations in the general population is unknown. The aim of this study was to identify novel SFTPC mutations that are associated with lung function...... pulmonary disease or interstitial lung disease. No Y106X heterozygotes suffered from asthma, chronic obstructive pulmonary disease (COPD), or interstitial lung disease. We identified two novel mutations in highly conserved areas of the SFTPC gene, and show that heterozygotes for the mutations have normal...... lung function and are unaffected by COPD and interstitial lung disease. A53T heterozygotes had increased asthma risk, but further research is required to conclusively determine whether this mutation is associated with asthma....

  16. Inhibition of pulmonary surfactant adsorption by serum and the mechanisms of reversal by hydrophilic polymers: theory

    DEFF Research Database (Denmark)

    Zasadzinski, Joseph A; Alig, T F; Alonso, Coralie

    2005-01-01

    A theory based on the Smolukowski analysis of colloid stability shows that the presence of charged, surface-active serum proteins at the alveolar air-liquid interface can severely reduce or eliminate the adsorption of lung surfactant from the subphase to the interface, consistent with the observa......A theory based on the Smolukowski analysis of colloid stability shows that the presence of charged, surface-active serum proteins at the alveolar air-liquid interface can severely reduce or eliminate the adsorption of lung surfactant from the subphase to the interface, consistent...... with the observations reported in the companion article (pages 1769-1779). Adding nonadsorbing, hydrophilic polymers to the subphase provides a depletion attraction between the surfactant aggregates and the interface, which can overcome the steric and electrostatic resistance to adsorption induced by serum....... The depletion force increases with polymer concentration as well as with polymer molecular weight. Increasing the surfactant concentration has a much smaller effect than adding polymer, as is observed. Natural hydrophilic polymers, like the SP-A present in native surfactant, or hyaluronan, normally present...

  17. Impact of a surfactant on the electroactivity of proteins at an aqueous-organogel microinterface array.

    Science.gov (United States)

    O'Sullivan, Shane; Arrigan, Damien W M

    2013-02-05

    The impact of surfactant addition to the organic phase on the electroactivity of proteins at the aqueous-organogel interface was examined by voltammetry. The presence of bis(2-ethylhexyl)sulfosuccinate (AOT) in the organogel phase, as the sodium salt, caused marked changes in the peak currents for myoglobin detection. The protein desorption voltammetric peak exhibited a 6-fold increase in the current compared to the corresponding experiment without surfactant. Interfacial coverage showed a 17-fold increase in the adsorbed protein at the interface, from 50 pmol cm(-2), in the absence of surfactant, to 850 pmol cm(-2), in the presence of 10 mM surfactant. Additionally, the presence of the surfactant resulted in a second pair of adsorption/desorption peaks at lower potentials and in a change in the capacitance of the system. The formation of surfactant-protein and surfactant-protein-organic anion deposits is proposed on the basis of these features, leading to increased voltammetric signals for myoglobin, hemoglobin, and cytochrome c. The mechanism of protein-surfactant interaction was probed by using the surfactant as the anion in the organic phase electrolyte salt. Repetitive cyclic voltammetry of cytochrome c showed that in the presence of surfactant there was an enhancement of the signal, caused by a buildup of the protein-surfactant-electrolyte anion assembly at the interface. These findings provide the basis for surfactant-modified interfaces to enhance the electroanalytical performance for protein detection.

  18. Progress in pulmonary surfactant-associated protein A in lung injury after cardiopulmonary bypass%肺表面活性物质相关蛋白A在体外循环后肺损伤中作用的研究进展

    Institute of Scientific and Technical Information of China (English)

    经俊; 李元海

    2015-01-01

    Background Lung injury after cardiopulmonary bypass (CPB) is a severe complication ofcardiac surgery,which is closely related to the rate of heart surgery and postoperative mortality.The effect of pulmonary surfactant-associated protein A (SP-A) in lung injury after CPB has been paid more attention by scientists recently.Objective To provide theoretic basis for clinical and basic,were reviewed the research process of the effects of SP-A in lung injury after CPB.Content Molecular structures,genes,receptors,regulation and physiological role of SP-A and the research process of effects of SP-A in lung injury after CPB were all reviewed.Trend With the development of molecular biology techniques,cloned or synthetic human SP-A,and the help of construction of vector for eukaryotic cells in vivo expression,SP-A become a new direction of treatment of lung injury after CPB.%背景 体外循环(cardiopulmonary bypass,CPB)后肺损伤是心脏手术重要的并发症,它与术后死亡率和心脏手术成功率有密切关系,而肺表面活性物质相关蛋白A(pulmonary surfactant-associated protein A,SP-A)在CPB后肺损伤中的作用近年来受到关注. 目的 对SP-A在CPB后肺损伤中作用的最新研究进展进行综述,为临床基础研究提供理论依据.内容 介绍SP-A的分子结构、基因、受体、调控及生理作用,重点阐述SP-A在CPB后肺损伤中的研究进展. 趋向 随着分子生物学技术的发展,克隆或合成人类SP-A、构建载体在体内进行真核细胞表达成为可能,为治疗CPB后肺损伤提供了一个新的发展方向.

  19. Surfactant gene polymorphisms and interstitial lung diseases

    Directory of Open Access Journals (Sweden)

    Pantelidis Panagiotis

    2001-11-01

    Full Text Available Abstract Pulmonary surfactant is a complex mixture of phospholipids and proteins, which is present in the alveolar lining fluid and is essential for normal lung function. Alterations in surfactant composition have been reported in several interstitial lung diseases (ILDs. Furthermore, a mutation in the surfactant protein C gene that results in complete absence of the protein has been shown to be associated with familial ILD. The role of surfactant in lung disease is therefore drawing increasing attention following the elucidation of the genetic basis underlying its surface expression and the proof of surfactant abnormalities in ILD.

  20. Production Technology and Physicochemical Properties of Composition Containing Surfactant Proteins

    Directory of Open Access Journals (Sweden)

    Valery V. Novochadov

    2016-06-01

    Full Text Available The article describes a production method of substance containing great amount of phospolipids (up to 36 % and surfactant proteins (up to 2 % in terms of lyophilisate composition. Basic physical and chemical characteristics of the substance (density, viscosity, surface tension and the coefficient of sliding friction indicate a high lubricant capacity of the derived product. These properties are kept when mixed with native human synovial fluid in the ratio of 1 to 9 inclusive. The obtained data allows to consider the derived composition, containing surfactant proteins and phospholipids, a variety of bionic lubricant suitable for testing as a potential equivalent of synovial fluid which can be used in traumatology and orthopedics, a cosmetic component or agent which increases the stability of the cell suspension during culturing in bioreactors.

  1. Surfactant protein D (SP-D) deficiency is attenuated in humanised mice expressing the Met(11)Thr short nucleotide polymorphism of SP-D

    DEFF Research Database (Denmark)

    Knudsen, Lars; Ochs, Katharina; Boxler, Laura;

    2013-01-01

    Surfactant protein D (SP-D) is part of the innate immune system involved in lung homeostasis. SP-D knockout mice show accumulations of foamy alveolar macrophages, alveolar lipoproteinosis and pulmonary emphysema. Three single nucleotide polymorphisms (SNPs) have been described in the coding...

  2. Complexation between dodecyl sulfate surfactant and zein protein in solution.

    Science.gov (United States)

    Ruso, Juan M; Deo, Namita; Somasundaran, P

    2004-10-12

    Interactions between sodium dodecyl sulfate and zein protein, a model system for the understanding of the effect of surfactants on skin, were investigated using a range of techniques involving UV-vis spectroscopy, TOC (total organic carbon analysis), electrophoresis, and static and dynamic light scattering. Zein protein was solubilized by SDS. The adsorption of SDS onto insoluble protein fraction caused the zeta potential of the complex to become more negative. From these values, we calculated the Gibbs energy of absorption, which decreases when the SDS concentration is raised. Finally the structure of the complex, based on the analysis by static and dynamic light scattering, is proposed to be rod like.

  3. Transport of nanoparticles across pulmonary surfactant monolayer: a molecular dynamics study.

    Science.gov (United States)

    Xu, Yan; Deng, Li; Ren, Hao; Zhang, Xianren; Huang, Fang; Yue, Tongtao

    2017-07-21

    Pulmonary nanodrug delivery is an emerging concept, especially for targeted lung cancer therapy. Once inhaled, the nanoparticles (NPs) acting as drug carriers need to efficiently cross the pulmonary surfactant monolayer (PSM) of lung alveoli, which act as the first barrier for external particles entering the lung. Herein, by performing molecular dynamics simulations, we study how inhaled NPs interact with the PSM, particularly focusing on the transport of NPs with different properties across the PSM. While hydrophilic NPs translocate directly across the PSM, transport of hydrophobic NPs is achieved as the PSM wraps them. Intriguingly, when hydrophilic NPs are decorated with lipid molecules (LCNPs), they are wrapped by the PSM efficiently with mild PSM perturbation. Moreover, the structure formed is like a vesicle, which will likely fuse with cell membranes to accomplish the transport of hydrophilic NPs into secondary organs. This behavior makes the LCNP a prospective candidate for pulmonary nanodrug delivery. Herein, the effects of the physical properties of LCNPs on their transport are investigated. Increasing the LCNP size promotes its wrapping by reducing the PSM bending energy. The binding energy that drives transport can be strengthened by increasing the lipid coating density and the lipid tail length, both of which also reduce the risk of PSM rupture during transport. These results should help researchers understand how to better use surface decorations to achieve efficient pulmonary entry, which may provide useful guidance for the design of nano-based platforms for inhaled drug delivery.

  4. Tuning of protein-surfactant interaction to modify the resultant structure.

    Science.gov (United States)

    Mehan, Sumit; Aswal, Vinod K; Kohlbrecher, Joachim

    2015-09-01

    Small-angle neutron scattering and dynamic light scattering studies have been carried out to examine the interaction of bovine serum albumin (BSA) protein with different surfactants under varying solution conditions. We show that the interaction of anionic BSA protein (pH7) with surfactant and the resultant structure are strongly modified by the charge head group of the surfactant, ionic strength of the solution, and mixed surfactants. The protein-surfactant interaction is maximum when two components are oppositely charged, followed by components being similarly charged through the site-specific binding, and no interaction in the case of a nonionic surfactant. This interaction of protein with ionic surfactants is characterized by the fractal structure representing a bead-necklace structure of micellelike clusters adsorbed along the unfolded protein chain. The interaction is enhanced with ionic strength only in the case of site-specific binding of an anionic surfactant with an anionic protein, whereas it is almost unchanged for other complexes of cationic and nonionic surfactants with anionic proteins. Interestingly, the interaction of BSA protein with ionic surfactants is significantly suppressed in the presence of nonionic surfactant. These results with mixed surfactants thus can be used to fold back the unfolded protein as well as to prevent surfactant-induced protein unfolding. For different solution conditions, the results are interpreted in terms of a change in fractal dimension, the overall size of the protein-surfactant complex, and the number of micelles attached to the protein. The interplay of electrostatic and hydrophobic interactions is found to govern the resultant structure of complexes.

  5. Effect of vasoactive intestinal peptide on pulmonary surfactants phospholipid synthesis in lung explants

    Institute of Scientific and Technical Information of China (English)

    Lian LI; Zi-qiang LUO; Fu-wen ZHOU; Dan-dan FENG; Cha-xiang GUAN; Chang-qing ZHANG; Xiu-hong SUN

    2004-01-01

    AIM: To investigate the effect of vasoactive intestinal peptide (VIP) on pulmonary surfactants (PS) phospholipid synthesis in cultured lung explants. METHODS: Lung explants were cultured with serum-free medium, [methyl-3H]choline incorporation, total phospholipid, phosphatidylcholine, activity of choline-phosphate cytidylyltransferase (CCT) and CCTα mRNA level in lung explants were determined. RESULTS: (1) VIP (10-10-10-7 mol/L) for 16 h promoted [methyl-3H]choline incorporation in dose dependence and VIP (10-8 mol/L) for 2 h-16 h promoted [methylz3H]choline incorporation in time dependence. (2) VIP (10-8 mol/L) enhanced the contents of total phospholipidsand phosphatidylcholine in lung explants. (3) VIP (10-10-10-7 mol/L) elevated microsomal CCT activity of lung explants in dose dependence. (4) VIP (10-8 mol/L) increased expression of CCTα mRNA in lung explants and alveolar type Ⅱ cells (ATII). (5) [D-P-Cl-Phe(6)-Leu(17)]-VIP (10-6 mol/L), a VIP receptors antagonist, abolished the increase of [3H]choline incorporation, microsomal CCT activity and CCTα mRNA level induced by VIP (10-8 mol/L) in lung explants. CONCLUSION: VIP could enhance synthesis of phosphatidylcholine, the major component of pulmonary surfactants by enhancing microsomal CCT activity and CCTα mRNA level via VIP receptormediated pathway.

  6. Pulmonary toxicity of trichloroethylene: induction of changes in surfactant phospholipids and phospholipase A2 activity in the mouse lung.

    Science.gov (United States)

    Scott, J E; Forkert, P G; Oulton, M; Rasmusson, M G; Temple, S; Fraser, M O; Whitefield, S

    1988-08-01

    Trichloroethylene (TCE) is a common organic solvent in use as a dry cleaning agent as well as an inhalant anesthetic. Nevertheless the effects of this material on the pulmonary surfactant which prevents alveolar collapse at maximal expiration is not known. Therefore, we have examined the effect of TCE on the intra- and extracellular surfactant pools and the activity of phospholipase A2, an enzyme which controls the remodeling of phosphatidylcholine to dipalmitoylphosphatidylcholine, the primary constituent of the pulmonary surfactant. Male CD-1 mice were treated ip with 2500 or 3000 mg/kg TCE. Twenty-four hours later mice were anesthetized and the lungs lavaged. Mice were then killed, the lungs perfused and excised, and subcellular fractions including lamellar bodies prepared. Some lungs were prepared for ultrastructural examination. Phospholipase A2 was assayed in all subcellular fractions. Phospholipid was assayed in the lavage (extracellular surfactant) and the lamellar bodies (intracellular surfactant). TCE (2500 mg/kg) caused selective exfoliation of Clara cells. However, only the dose of 3000 mg/kg TCE produced a significant decrease in the intracellular surfactant phospholipid. Minimal changes occurred in the phospholipid profiles. Phospholipase A2 specific activity was significantly decreased at both dosages within the lung microsomal fraction. In addition after treatment with 3000 mg/kg TCE the enzyme activity in the lamellar body fraction was significantly increased. These data suggest that inhalation of TCE may damage the enzymes which are responsible for synthesizing the pulmonary surfactant resulting in lower amounts of surfactant being stored and available for secretion into the alveolus.

  7. Pulmonary haptoglobin (pHp) is part of the surfactant system in the human lung.

    Science.gov (United States)

    Abdullah, Mahdi; Goldmann, Torsten

    2012-11-20

    Since the existence of pHp was demonstrated, it has been shown that this molecule and its receptor CD163 are regulated by different stimuli. Furthermore, a comparably fast secretion of pHp was described as well as the immuno-stimulatory effects. The intention of this study was to elucidate the role of pHp in the human lungs further. Here we show, by means of confocal microscopy and immune-electron-microscopy, a clear co-localization of pHp with surfactant protein-B in lamellar bodies of alveolar epithelial cells type II. These results are underlined by immunohistochemical stainings in differently fixed human lung tissues, which show pHp in vesicular and released form. The images of the released form resemble the intended position of surfactant in the human alveolus. pHp is secreted by Alveolar epithelial cells type II as previously shown. Moreover, pHp is co-localized with Surfactant protein-B. We conclude that the presented data shows that pHp is a native part of the surfactant system in the human lung. http://www.diagnosticpathology.diagnomx.eu/vs/2563584738239912.

  8. Effects of continuous tracheal gas insufflation during pressure limited ventilation on pulmonary surfactant in rabbits with acute lung injury

    Institute of Scientific and Technical Information of China (English)

    ZHU Guang-fa; ZHANG Wei; ZONG Hua; LIANG Ying

    2006-01-01

    Background Pulmonary surfactant dysfunction may contribute to the development of ventilator induced lung injury (VILI). Tracheal gas insufflation (TGI) is a technique in which fresh gas is introduced into the trachea and augment ventilation by reducing the dead space of ventilatory system, reducing ventilatory pressures and tidal volume (VT) while maintaining constant partial arterial CO2 pressure (PaCO2). We hypothesised that TGI limited peak inspiratory pressure (PIP) and VT and would minimize conventional mechanical ventilation (CMV) induced pulmonary surfactant dysfunction and thereby attenuate VILI in rabbits with acute lung injury (ALI).Methods ALI was induced by intratracheal administration of lipopolysaccharide in anaesthetized, ventilated healthy adult rabbits randomly assigned to continuous TGI at 0.5 L/min (TGI group) or CMV group (n=8 for each group), and subsequently ventilated with limited PIP and VT to maintain PaCO2 within 35 to 45 mmHg for 4 hours. Physiological dead space to VT ratio (VD/VT), dynamic respiratory compliance (Cdyn) and partial arterial O2 pressure (PaO2) were monitored. After ventilation, lungs were analysed for total phospholipids (TPL), total proteins (TP), pulmonary surfactant small to large aggregates ratio (SA/LA) in bronchoalveolar lavage fluid (BALF) and for determination of alveolar volume density (Vv), myeloperoxidase and interleukin (IL)-8.Results TGI resulted in significant (P<0.05 or P<0.01) decrease in PIP [(22.4±1.8) cmH2O vs (29.5±1.1) cmH2O], VT [(6.9±1.3) ml/kg vs (9.8±1.11) ml/kg], VD/VT [(32±5)% vs (46±2)%], TP [(109±22) mg/kg vs (187±25) mg/kg], SA/LA (2.5±0.4 vs 5.4±0.7), myeloperoxidase [(6.2±0.5) U/g tissue vs (12.3±0.8) U/g tissue] and IL-8 [(987±106) ng/g tissue vs (24±3) mN/m] of BALF, and significant (P<0.05) increase in Cdyn [(0.47±0.02) ml ·cmH2O-1 ·kg-1 vs (0.31±0.02) ml ·cmH2O-1 ·kg-1], PaO2 [(175±24) mmHg vs (135±26) mmHg],TPL/TP (52±8 vs 33±11) and Vv (0.65±0.05 vs 0

  9. Interplay of mycolic acids, antimycobacterial compounds and pulmonary surfactant membrane: a biophysical approach to disease.

    Science.gov (United States)

    Pinheiro, Marina; Giner-Casares, Juan J; Lúcio, Marlene; Caio, João M; Moiteiro, Cristina; Lima, José L F C; Reis, Salette; Camacho, Luis

    2013-02-01

    This work focuses on the interaction of mycolic acids (MAs) and two antimycobacterial compounds (Rifabutin and N'-acetyl-Rifabutin) at the pulmonary membrane level to convey a biophysical perspective of their role in disease. For this purpose, accurate biophysical techniques (Langmuir isotherms, Brewster angle microscopy, and polarization-modulation infrared reflection spectroscopy) and lipid model systems were used to mimic biomembranes: MAs mimic bacterial lipids of the Mycobacterium tuberculosis (MTb) membrane, whereas Curosurf® was used as the human pulmonary surfactant (PS) membrane model. The results obtained show that high quantities of MAs are responsible for significant changes on PS biophysical properties. At the dynamic inspiratory surface tension, high amounts of MAs decrease the order of the lipid monolayer, which appears to be a concentration dependent effect. These results suggest that the amount of MAs might play a critical role in the initial access of the bacteria to their targets. Both molecules also interact with the PS monolayer at the dynamic inspiratory surface. However, in the presence of higher amounts of MAs, both compounds improve the phospholipid packing and, therefore, the order of the lipid surfactant monolayer. In summary, this work discloses the putative protective effects of antimycobacterial compounds against the MAs induced biophysical impairment of PS lipid monolayers. These protective effects are most of the times overlooked, but can constitute an additional therapeutic value in the treatment of pulmonary tuberculosis (Tb) and may provide significant insights for the design of new and more efficient anti-Tb drugs based on their behavior as membrane ordering agents.

  10. Amphiphilic biopolymers (amphibiopols) as new surfactants for membrane protein solubilization

    Science.gov (United States)

    Duval-Terrié, Caroline; Cosette, Pascal; Molle, Gérard; Muller, Guy; Dé, Emmanuelle

    2003-01-01

    The aim of this study was to develop new surfactants for membrane protein solubilization, from a natural, biodegradable polymer: the polysaccharide pullulan. A set of amphiphilic pullulans (HMCMPs), differing in hydrophobic modification ratio, charge ratio, and the nature of the hydrophobic chains introduced, were synthesized and tested in solubilization experiments with outer membranes of Pseudomonas fluorescens. The membrane proteins were precipitated, and then resolubilized with various HMCMPs. The decyl alkyl chain (C10) was the hydrophobic graft that gave the highest level of solubilization. Decyl alkyl chain-bearing HMCMPs were also able to extract integral membrane proteins from their lipid environment. The best results were obtained with an amphiphilic pullulan bearing 18% decyl groups (18C10). Circular dichroism spectroscopy and membrane reconstitution experiments were used to test the structural and functional integrity of 18C10-solubilized proteins (OmpF from Escherichia coli and bacteriorhodopsin from Halobacterium halobium). Whatever their structure type (α or β), 18C10 did not alter either the structure or the function of the proteins analyzed. Thus, HMCMPs appear to constitute a promising new class of polymeric surfactants for membrane protein studies. PMID:12649425

  11. Lung surfactant protein A (SP-A) interactions with model lung surfactant lipids and an SP-B fragment.

    Science.gov (United States)

    Sarker, Muzaddid; Jackman, Donna; Booth, Valerie

    2011-06-07

    Surfactant protein A (SP-A) is the most abundant protein component of lung surfactant, a complex mixture of proteins and lipids. SP-A performs host defense activities and modulates the biophysical properties of surfactant in concerted action with surfactant protein B (SP-B). Current models of lung surfactant mechanism generally assume SP-A functions in its octadecameric form. However, one of the findings of this study is that when SP-A is bound to detergent and lipid micelles that mimic lung surfactant phospholipids, it exists predominantly as smaller oligomers, in sharp contrast to the much larger forms observed when alone in water. These investigations were carried out in sodium dodecyl sulfate (SDS), dodecylphosphocholine (DPC), lysomyristoylphosphatidylcholine (LMPC), lysomyristoylphosphatidylglycerol (LMPG), and mixed LMPC + LMPG micelles, using solution and diffusion nuclear magnetic resonance (NMR) spectroscopy. We have also probed SP-A's interaction with Mini-B, a biologically active synthetic fragment of SP-B, in the presence of micelles. Despite variations in Mini-B's own interactions with micelles of different compositions, SP-A is found to interact with Mini-B in all micelle systems and perhaps to undergo a further structural rearrangement upon interacting with Mini-B. The degree of SP-A-Mini-B interaction appears to be dependent on the type of lipid headgroup and is likely mediated through the micelles, rather than direct binding.

  12. An insight into the immune roles of surfactant proteins, SP-A and SP-D

    Directory of Open Access Journals (Sweden)

    Annapurna eNayak

    2012-06-01

    Full Text Available Pulmonary surfactant proteins, SP-A and SP-D, are hydrophilic collagen-containing calcium-dependent lectins, which appear to have a range of innate immune functions at pulmonary as well as extrapulmonary sites. These proteins bind to target ligands on pathogens, allergens and apoptotic cells via C-terminal carbohydrate recognition domains while the collagen region brings about the effector functions. SP-A and SP-D deals with various pathogens triggering a range of innate immune mechanisms such as agglutination/aggregation, enhancement of phagocytosis and killing reactions, and growth inhibition. SP-A and SP-D have also been involved in the control of pulmonary inflammation including allergy and asthma, and hence, they are likely to central issues in a range of pathological situations. There is also emerging evidence to suggest that SP-A and SP-D are capable of linking innate immunity with adaptive immunity that includes modulation of dendritic cell function and helper T cell polarisation. It is clear now that SP-A and SP-D are potent innate immune molecules in the lungs. This review is a summary of their immunological properties in general and their importance in human health and disease.

  13. Surfactant protein D in the female genital tract

    DEFF Research Database (Denmark)

    Leth-Larsen, Rikke; Floridon, C; Nielsen, O;

    2004-01-01

    Surfactant protein D (SP-D) plays a role in innate immunity against various pathogens and in vivo studies have demonstrated that SP-D also has anti-inflammatory properties. SP-D was originally demonstrated in alveolar type II cells, but recent studies have shown extrapulmonary expression of SP......-D indicating a systemic role for the protein. This study describes the presence of SP-D in the female genital tract, the placenta and in amniotic fluid using immunohistochemistry and enzyme-linked immunosorbent assay. SP-D was observed in cells lining surface epithelium and secretory glands in the vagina...

  14. Distinct changes in pulmonary surfactant homeostasis in common beta-chain-and GM-CSF-deficient mice

    NARCIS (Netherlands)

    Reed, JA; Ikegami, M; Robb, L; Begley, CG; Ross, G; Whitsett, JA

    Pulmonary alveolar proteinosis (PAP) is caused by inactivation of either granulocyte-macrophage colony-stimulating factor (GMCSF) or GM receptor common beta-chain (beta(c)) genes in mice [GM(-/-), beta(c)(-/-)], demonstrating a critical role of GM-CSF signaling in surfactant homeostasis. To

  15. Compositional and structural characterization of monolayers and bilayers composed of native pulmonary surfactant from wild type mice

    DEFF Research Database (Denmark)

    Bernardino de la Serna, Jorge; Hansen, Soren; Berzina, Zane

    2013-01-01

    This work comprises a structural and dynamical study of monolayers and bilayers composed of native pulmonary surfactant from mice. Spatially resolved information was obtained using fluorescence (confocal, wide field and two photon excitation) and atomic force microscopy methods. Lipid mass...... spectrometry experiments were also performed in order to obtain relevant information on the lipid composition of this material. Bilayers composed of mice pulmonary surfactant showed coexistence of distinct domains at room temperature, with morphologies and lateral packing resembling the coexistence of liquid...... ordered (lo)/liquid disordered (ld)-like phases reported previously in porcine lung surfactant. Interestingly, the molar ratio of saturated (mostly DPPC)/non-saturated phospholipid species and cholesterol measured in the innate material corresponds with that of a DOPC/DPPC/cholesterol mixture showing lo...

  16. Expression profiles of hydrophobic surfactant proteins in children with diffuse chronic lung disease

    Directory of Open Access Journals (Sweden)

    Guttentag Susan

    2005-07-01

    Full Text Available Abstract Background Abnormalities of the intracellular metabolism of the hydrophobic surfactant proteins SP-B and SP-C and their precursors may be causally linked to chronic childhood diffuse lung diseases. The profile of these proteins in the alveolar space is unknown in such subjects. Methods We analyzed bronchoalveolar lavage fluid by Western blotting for SP-B, SP-C and their proforms in children with pulmonary alveolar proteinosis (PAP, n = 15, children with no SP-B (n = 6, children with chronic respiratory distress of unknown cause (cRD, n = 7, in comparison to children without lung disease (n = 15 or chronic obstructive bronchitis (n = 19. Results Pro-SP-B of 25–26 kD was commonly abundant in all groups of subjects, suggesting that their presence is not of diagnostic value for processing defects. In contrast, pro-SP-B peptides cleaved off during intracellular processing of SP-B and smaller than 19–21 kD, were exclusively found in PAP and cRD. In 4 of 6 children with no SP-B, mutations of SFTPB or SPTPC genes were found. Pro-SP-C forms were identified at very low frequency. Their presence was clearly, but not exclusively associated with mutations of the SFTPB and SPTPC genes, impeding their usage as candidates for diagnostic screening. Conclusion Immuno-analysis of the hydrophobic surfactant proteins and their precursor forms in bronchoalveolar lavage is minimally invasive and can give valuable clues for the involvement of processing abnormalities in pediatric pulmonary disorders.

  17. The importance of surfactant on the development of neonatal pulmonary diseases Síndrome da angustia respiratória aguda e proteinose alveolar congênita

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    Priscila Pinheiro Ribeiro Lyra

    2007-01-01

    Full Text Available Pulmonary surfactant is a substance composed of a lipoprotein complex that is essential to pulmonary function. Pulmonary surfactant proteins play an important role in the structure, function, and metabolism of surfactant; 4 specific surfactant proteins have been identified: surfactant proteins-A, surfactant proteins-B, surfactant proteins-C, and surfactant proteins-D. Clinical, epidemiological, and biochemical evidence suggests that the etiology of respiratory distress syndrome is multifactorial with a significant genetic component. There are reports about polymorphisms and mutations on the surfactant protein genes, especially surfactant proteins-B, that may be associated with respiratory distress syndrome, acute respiratory distress syndrome, and congenital alveolar proteinosis. Individual differences regarding respiratory distress syndrome and acute respiratory distress syndrome as well as patient response to therapy might reflect phenotypic diversity due to genetic variation, in part. The study of the differences between the allelic variants of the surfactant protein genes can contribute to the understanding of individual susceptibility to the development of several pulmonary diseases. The identification of the polymorphisms and mutations that are indeed important for the pathogenesis of the diseases related to surfactant protein dysfunction, leading to the possibility of genotyping individuals at increased risk, constitutes a new research field. In the future, findings in these endeavors may enable more effective genetic counseling as well as the development of prophylactic and therapeutic strategies that would provide a real impact on the management of newborns with respiratory distress syndrome and other pulmonary diseases.O surfactante pulmonar é uma substância composta por um complexo lipoprotéico essencial para a função pulmonar normal. As proteínas do surfactante têm importante papel na estrutura, função e metabolismo do

  18. Surfactant Protein B Intron 4 Variation in German Patients with COPD and Acute Respiratory Failure

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    Carola Seifart

    2002-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is a major health problem. Genetic factors that contribute to the disease have been postulated. The pulmonary surfactant protein B (SP-B, which is essential for normal lung function, is considered as a candidate gene for COPD in this case-control study. We studied the SP-B intron 4 size variants in 346 individuals. This group consisted of 118 patients with chronic bronchitis or COPD, including 24 patients with acute respiratory failure (ARF in COPD, 118 matched controls without pulmonary disease and 110 healthy individuals (population control. The frequency of intron 4 variants was similar in either control group (10.9%, 14.4% respectively, with a small increase in the COPD group (18.6%. This increase was due to a high increase of intron 4 variants in the ARF subgroup (37.5%, p = 0.003, OR 4.9, 95% CI: 1.76–13.6. The data indicate that SP-B intron 4 variants may associate with increased risk of ARF in COPD and may be used as a marker of susceptibility in this disease subgroup.

  19. Effects of graphene oxide nanosheets on the ultrastructure and biophysical properties of the pulmonary surfactant film.

    Science.gov (United States)

    Hu, Qinglin; Jiao, Bao; Shi, Xinghua; Valle, Russell P; Zuo, Yi Y; Hu, Guoqing

    2015-11-21

    Graphene oxide (GO) is the most common derivative of graphene and has been used in a large range of biomedical applications. Despite considerable progress in understanding its cytotoxicity, its potential inhalation toxicity is still largely unknown. As the pulmonary surfactant (PS) film is the first line of host defense, interaction with the PS film determines the fate of the inhaled nanomaterials and their potential toxicity. Using a coarse-grained molecular dynamics model, we reported, for the first time, a novel mechanism of toxicity caused by the inhaled GO nanosheets. Upon deposition, the GO nanosheets induce pores in the PS film and thus have adverse effects on the ultrastructure and biophysical properties of the PS film. Notably, the pores induced by GO nanosheets result in increasing the compressibility of the PS film, which is an important indication of surfactant inhibition. In vitro experiments have also been conducted to study the interactions between GO and animal-derived natural PS films, qualitatively confirming the simulation results.

  20. Spontaneous surface self-assembly in protein-surfactant mixtures: interactions between hydrophobin and ethoxylated polysorbate surfactants.

    Science.gov (United States)

    Tucker, Ian M; Petkov, Jordan T; Penfold, Jeffrey; Thomas, Robert K; Li, Peixun; Cox, Andrew R; Hedges, Nick; Webster, John R P

    2014-05-01

    The synergistic interactions between certain ethoxylated polysorbate nonionic surfactants and the protein hydrophobin result in spontaneous self-assembly at the air-water interface to form layered surface structures. The surface structures are characterized using neutron reflectivity. The formation of the layered surface structures is promoted by the hydrophobic interaction between the polysorbate alkyl chain and the hydrophobic patch on the surface of the globular hydrophobin and the interaction between the ethoxylated sorbitan headgroup and hydrophilic regions of the protein. The range of the ethoxylated polysorbate concentrations over which the surface ordering occurs is a maximum for the more hydrophobic surfactant polyoxyethylene(8) sorbitan monostearate. The structures at the air-water interface are accompanied by a profound change in the wetting properties of the solution on hydrophobic substrates. In the absence of the polysorbate surfactant, hydrophobin wets a hydrophobic surface, whereas the hydrophobin/ethoxylated polysorbate mixtures where multilayer formation occurs result in a significant dewetting of hydrophobic surfaces. The spontaneous surface self-assembly for hydrophobin/ethoxylated polysorbate surfactant mixtures and the changes in surface wetting properties provide a different insight into protein-surfactant interactions and potential for manipulating surface and interfacial properties and protein surface behavior.

  1. Essential Regulation of Lung Surfactant Homeostasis by the Orphan G Protein-Coupled Receptor GPR116

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    Mi Young Yang

    2013-05-01

    Full Text Available GPR116 is an orphan seven-pass transmembrane receptor whose function has been unclear. Global disruption of the Gpr116 gene in mice revealed an unexpected, critical role for this receptor in lung surfactant homeostasis, resulting in progressive accumulation of surfactant lipids and proteins in the alveolar space, labored breathing, and a reduced lifespan. GPR116 expression analysis, bone marrow transplantation studies, and characterization of conditional knockout mice revealed that GPR116 expression in ATII cells is required for maintaining normal surfactant levels. Aberrant packaging of surfactant proteins with lipids in the Gpr116 mutant mice resulted in compromised surfactant structure, function, uptake, and processing. Thus, GPR116 plays an indispensable role in lung surfactant homeostasis with important ramifications for the understanding and treatment of lung surfactant disorders.

  2. Essential Regulation of Lung Surfactant Homeostasis by the Orphan G-protein Coupled Receptor GPR116

    Science.gov (United States)

    Yang, Mi Young; Hilton, Mary Beth; Seaman, Steven; Haines, Diana C.; Nagashima, Kunio; Burks, Christina M.; Tessarollo, Lino; Ivanova, Pavlina T.; Brown, H. Alex; Umstead, Todd M.; Floros, Joanna; Chroneos, Zissis C.; St. Croix, Brad

    2013-01-01

    SUMMARY GPR116 is an orphan seven-pass transmembrane receptor of previously unknown function. Global disruption of the Gpr116 gene in mice revealed an unexpected, critical role for this receptor in lung surfactant homeostasis, resulting in progressive accumulation of surfactant lipids and proteins in the alveolar space, labored breathing, and a reduced lifespan. GPR116 expression analysis, bone marrow transplantation studies and characterization of conditional knockout mice revealed that GPR116 expression in ATII cells is required for maintaining normal surfactant levels. Aberrant packaging of surfactant proteins with lipids in the Gpr116 mutant mice resulted in compromised surfactant structure, function, uptake, and processing. Thus, GPR116 plays an indispensable role in lung surfactant homeostasis with important ramifications for the understanding and treatment of lung surfactant disorders. PMID:23684610

  3. Essential regulation of lung surfactant homeostasis by the orphan G protein-coupled receptor GPR116.

    Science.gov (United States)

    Yang, Mi Young; Hilton, Mary Beth; Seaman, Steven; Haines, Diana C; Nagashima, Kunio; Burks, Christina M; Tessarollo, Lino; Ivanova, Pavlina T; Brown, H Alex; Umstead, Todd M; Floros, Joanna; Chroneos, Zissis C; St Croix, Brad

    2013-05-30

    GPR116 is an orphan seven-pass transmembrane receptor whose function has been unclear. Global disruption of the Gpr116 gene in mice revealed an unexpected, critical role for this receptor in lung surfactant homeostasis, resulting in progressive accumulation of surfactant lipids and proteins in the alveolar space, labored breathing, and a reduced lifespan. GPR116 expression analysis, bone marrow transplantation studies, and characterization of conditional knockout mice revealed that GPR116 expression in ATII cells is required for maintaining normal surfactant levels. Aberrant packaging of surfactant proteins with lipids in the Gpr116 mutant mice resulted in compromised surfactant structure, function, uptake, and processing. Thus, GPR116 plays an indispensable role in lung surfactant homeostasis with important ramifications for the understanding and treatment of lung surfactant disorders. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  4. In vivo evaluation of the inhibitory capacity of human plasma on exogenous surfactant function

    NARCIS (Netherlands)

    B.F. Lachmann (Burkhard); E.P. Eijking (Eric); K.L. So; D.A.M.P.J. Gommers (Diederik)

    1994-01-01

    textabstractObjective: The adult respiratory distress syndrome (ARDS) and neonatal respiratory distress syndrome (RDS) are characterized by high permeability pulmonary edema which contains plasma-derived proteins inhibiting pulmonary surfactant function. Currently, discussion continues as to what do

  5. SP-A-enriched surfactant for treatment of rat lung transplants with SP-A deficiency after storage and reperfusion

    NARCIS (Netherlands)

    Erasmus, ME; Hofstede, GJH; Petersen, AH; Batenburg, JJ; Haagsman, HP; Oetomo, SB; Prop, J

    2002-01-01

    Background. The function of pulmonary surfactant is affected by lung transplantation, contributing to impaired lung transplant function. A decreased amount of surfactant protein-A (SP-A) after reperfusion is believed to contribute to the impaired surfactant function. Surfactant treatment has been sh

  6. Compositional and structural characterization of monolayers and bilayers composed of native pulmonary surfactant from wild type mice.

    Science.gov (United States)

    Bernardino de la Serna, Jorge; Hansen, Soren; Berzina, Zane; Simonsen, Adam C; Hannibal-Bach, Hans K; Knudsen, Jens; Ejsing, Christer S; Bagatolli, Luis A

    2013-11-01

    This work comprises a structural and dynamical study of monolayers and bilayers composed of native pulmonary surfactant from mice. Spatially resolved information was obtained using fluorescence (confocal, wide field and two photon excitation) and atomic force microscopy methods. Lipid mass spectrometry experiments were also performed in order to obtain relevant information on the lipid composition of this material. Bilayers composed of mice pulmonary surfactant showed coexistence of distinct domains at room temperature, with morphologies and lateral packing resembling the coexistence of liquid ordered (lo)/liquid disordered (ld)-like phases reported previously in porcine lung surfactant. Interestingly, the molar ratio of saturated (mostly DPPC)/non-saturated phospholipid species and cholesterol measured in the innate material corresponds with that of a DOPC/DPPC/cholesterol mixture showing lo/ld phase coexistence at a similar temperature. This suggests that at quasi-equilibrium conditions, key lipid classes in this complex biological material are still able to produce the same scaffold observed in relevant but simpler model lipid mixtures. Also, robust structural and dynamical similarities between mono- and bi-layers composed of mice pulmonary surfactant were observed when the monolayers reach a surface pressure of 30mN/m. This value is in line with theoretically predicted and recently measured surface pressures, where the monolayer-bilayer equivalence occurs in samples composed of single phospholipids. Finally, squeezed out material attached to pulmonary surfactant monolayers was observed at surface pressures near the beginning of the monolayer reversible exclusion plateau (~40mN/m). Under these conditions this material adopts elongated tubular shapes and displays ordered lateral packing as indicated by spatially resolved LAURDAN GP measurements.

  7. Correlations of Mechanical Stability, Morphology, Pulmonary Surfactant, and Phospholipid Content in the Developing Lamb Lung*

    Science.gov (United States)

    Brumley, George W.; Chernick, Victor; Hodson, W. Alan; Normand, Colin; Fenner, Axel; Avery, Mary Ellen

    1967-01-01

    Pressure-volume characteristics and surface tension measurements of the lamb of 120 to 130 days gestational age were typical of the mature lung in the upper lobes and the immature lung in the lower lobes. By term both upper and lower lobes had findings characteristic of the mature animal. Phospholipid concentration per milligram DNA and per cent saturated fatty acids on pulmonary phosphatidyl choline were relatively constant from 60 to 120 days gestational age; thereafter there was a significant increase in both measurements. These changes usually coincided with an increase in osmiophilic inclusion bodies in the large alveolar cell. A concentration of disaturated phosphatidyl choline per milligram DNA in excess of 0.170 mg per mg was associated with a minimal surface tension below 13 dynes per cm (p < 0.001). Newborn animal lungs contained over 3 times this critical concentration, whereas adult lungs contained 1.5 times this value. The excess disaturated phosphatidyl choline per milligram DNA may represent a reservoir of pulmonary surfactant. Images PMID:6025487

  8. 吸入沙美特罗替卡松粉剂对稳定期COPD患者血清SP-D浓度的影响%Effect of inhaled salmeterol/fluticasone on serum surfactant protein D in patients with stable chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    陈明勇; 陈勃江; 陈斌; 刘小英

    2012-01-01

    Objective To determine the effect of inhaled salmeterol/fluticasone on serum surfactant protein D(SP- D) in patients with stable chronic obstructive pulmonary disease (COPD).Methods 84 COPD patients were randomly divided into two groups; group 1 ( n =42) were treated with salmeterol (50 μg) alone,and group 2 ( n =42) with salmeterol/fluticasone (50 μg/500 μg),each patient inhaled twice daily for 12 weeks.Serum samples were taken at baseline and after 12 weeks of treatment.The levels of serum SP-Dwere detected using ELISA.Results The average serum SP-D for patients were significantly decreased from ( 148.2 ± 65.7 ) μg/L to (89.2 ± 53.2) μg/L ( P <0.05 ) in patients who inhaled salmeterol/fluticasone.The average serum SP D for patients who inhaled salmeterol alone was (143.5 ± 69.1) μg/L and ( 136.7 ± 59.5) μg/L at baseline and after inhaled salmeterol were not significant (P > 0.05).Conclusions The serum SP- D in patients with stable COPD decreases significantly after treatment with inhaled salmeterol/fluticasone,which may be a potential diagnostic biomarker for COPD treatment.%目的 探讨吸入沙美特罗替卡松粉剂对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)稳定期患者血清肺表面活性物质相关蛋白D(surfactant associated protein D,SP-D)浓度的影响.方法 选择Ⅲ级及Ⅳ级稳定期COPD患者84例,随机分为沙美特罗(50μg)和沙美特罗替卡松粉剂(50 μg/500 μg)两组,每组42例,每例患者均吸入2次/日,每次1吸,疗程12周.收集治疗前后血清标本各一份,采用ELISA法检测患者血清SP -D浓度.结果 治疗前后平均血清SP- D浓度吸入沙美特罗替卡松粉剂治疗组患者分别为(148.2 ±65.7)μg/L和(89.2±53.2) μg/L,治疗前后血清平均SP-D水平差异有统计学意义(P<0.05).单纯吸入沙美特罗粉剂组治疗前后患者血清SP-D浓度分别为(143.5±69.1)μg/L和(136.7±59.5)μg/L,治疗前后血清平均SP-D水

  9. Human surfactant protein A2 gene mutations impair dimmer/trimer assembly leading to deficiency in protein sialylation and secretion.

    Directory of Open Access Journals (Sweden)

    Yi Song

    Full Text Available Surfactant protein A2 (SP-A2 plays an essential role in surfactant metabolism and lung host defense. SP-A2 mutations in the carbohydrate recognition domain have been related to familial pulmonary fibrosis and can lead to a recombinant protein secretion deficiency in vitro. In this study, we explored the molecular mechanism of protein secretion deficiency and the subsequent biological effects in CHO-K1 cells expressing both wild-type and several different mutant forms of SP-A2. We demonstrate that the SP-A2 G231V and F198S mutants impair the formation of dimmer/trimer SP-A2 which contributes to the protein secretion defect. A deficiency in sialylation, but not N-linked glycosylation, is critical to the observed dimmer/trimer impairment-induced secretion defect. Furthermore, both mutant forms accumulate in the ER and form NP-40-insoluble aggregates. In addition, the soluble mutant SP-A2 could be partially degraded through the proteasome pathway but not the lysosome or autophagy pathway. Intriguingly, 4-phenylbutyrate acid (4-PBA, a chemical chaperone, alleviates aggregate formation and partially rescued the protein secretion of SP-A2 mutants. In conclusion, SP-A2 G231V and F198S mutants impair the dimmer/trimer assembly, which contributes to the protein sialylation and secretion deficiency. The intracellular protein mutants could be partially degraded through the proteasome pathway and also formed aggregates. The treatment of the cells with 4-PBA resulted in reduced aggregation and rescued the secretion of mutant SP-A2.

  10. Surfactant Protein-D-Encoding Gene Variant Polymorphisms Are Linked to Respiratory Outcome in Premature Infants

    DEFF Research Database (Denmark)

    Sorensen, Grith Lykke; Dahl, Marianne; Tan, Qihua

    2014-01-01

    OBJECTIVE: Associations between the genetic variation within or downstream of the surfactant protein-D-encoding gene (SFTPD), which encodes the collectin surfactant protein-D (SP-D) and may lead to respiratory distress syndrome or bronchopulmonary dysplasia, recently were reported. Our aim was to...

  11. Cryptococcus neoformans is resistant to surfactant protein A mediated host defense mechanisms.

    Directory of Open Access Journals (Sweden)

    Steven S Giles

    Full Text Available Initiation of a protective immune response to infection by the pathogenic fungus Cryptococcus neoformans is mediated in part by host factors that promote interactions between immune cells and C. neoformans yeast. Surfactant protein A (SP-A contributes positively to pulmonary host defenses against a variety of bacteria, viruses, and fungi in part by promoting the recognition and phagocytosis of these pathogens by alveolar macrophages. In the present study we investigated the role of SP-A as a mediator of host defense against the pulmonary pathogen, C. neoformans. Previous studies have shown that SP-A binds to acapsular and minimally encapsulated strains of C. neoformans. Using in vitro binding assays we confirmed that SP-A does not directly bind to a fully encapsulated strain of C. neoformans (H99. However, we observed that when C. neoformans was incubated in bronchoalveolar fluid, SP-A binding was detected, suggesting that another alveolar host factor may enable SP-A binding. Indeed, we discovered that SP-A binds encapsulated C. neoformans via a previously unknown IgG dependent mechanism. The consequence of this interaction was the inhibition of IgG-mediated phagocytosis of C. neoformans by alveolar macrophages. Therefore, to assess the contribution of SP-A to the pulmonary host defenses we compared in vivo infections using SP-A null mice (SP-A-/- and wild-type mice in an intranasal infection model. We found that the immune response assessed by cellular counts, TNFalpha cytokine production, and fungal burden in lungs and bronchoalveolar lavage fluids during early stages of infection were equivalent. Furthermore, the survival outcome of C. neoformans infection was equivalent in SP-A-/- and wild-type mice. Our results suggest that unlike a variety of bacteria, viruses, and other fungi, progression of disease with an inhalational challenge of C. neoformans does not appear to be negatively or positively affected by SP-A mediated mechanisms of

  12. Pulmonary clearance of 99mTc-DTPA: role of the pulmonary surfactant system.

    NARCIS (Netherlands)

    J.A.H. Bos (Jelle)

    1992-01-01

    textabstractIt is established that in a wide variety of acute and chronic lung diseases the integrity of the alveolar-capillary membrane is altered. Increased permeability of the barrier is thought to cause increased filtration of fluids and proteins into the alveoli and increased absorption of inha

  13. Surfactant protein d deficiency in mice is associated with hyperphagia, altered fat deposition, insulin resistance, and increased Basal endotoxemia

    DEFF Research Database (Denmark)

    Stidsen, Jacob V; Khorooshi, Reza; Rahbek, Martin K U

    2012-01-01

    Pulmonary surfactant protein D (SP-D) is a host defence lectin of the innate immune system that enhances clearance of pathogens and modulates inflammatory responses. Recently it has been found that systemic SP-D is associated with metabolic disturbances and that SP-D deficient mice are mildly obese...... with elevated levels of systemic bacterial lipopolysaccharide.In conclusion, our findings suggest that lack of SP-D mediates modulation of food intake not directly involving hypothalamic regulatory pathways. The resulting accumulation of adipose tissue was associated with insulin resistance. The data suggest SP...

  14. S-nitrosylation of surfactant protein-D controls inflammatory function.

    Directory of Open Access Journals (Sweden)

    Chang-Jiang Guo

    2008-11-01

    Full Text Available The pulmonary collectins, surfactant proteins A and D (SP-A and SP-D have been implicated in the regulation of the innate immune system within the lung. In particular, SP-D appears to have both pro- and anti-inflammatory signaling functions. At present, the molecular mechanisms involved in switching between these functions remain unclear. SP-D differs in its quaternary structure from SP-A and the other members of the collectin family, such as C1q, in that it forms large multimers held together by the N-terminal domain, rather than aligning the triple helix domains in the traditional "bunch of flowers" arrangement. There are two cysteine residues within the hydrophobic N terminus of SP-D that are critical for multimer assembly and have been proposed to be involved in stabilizing disulfide bonds. Here we show that these cysteines exist within the reduced state in dodecameric SP-D and form a specific target for S-nitrosylation both in vitro and by endogenous, pulmonary derived nitric oxide (NO within a rodent acute lung injury model. S-nitrosylation is becoming increasingly recognized as an important post-translational modification with signaling consequences. The formation of S-nitrosothiol (SNO-SP-D both in vivo and in vitro results in a disruption of SP-D multimers such that trimers become evident. SNO-SP-D but not SP-D, either dodecameric or trimeric, is chemoattractive for macrophages and induces p38 MAPK phosphorylation. The signaling capacity of SNO-SP-D appears to be mediated by binding to calreticulin/CD91. We propose that NO controls the dichotomous nature of this pulmonary collectin and that posttranslational modification by S-nitrosylation causes quaternary structural alterations in SP-D, causing it to switch its inflammatory signaling role. This represents new insight into both the regulation of protein function by S-nitrosylation and NO's role in innate immunity.

  15. Molecular biological characterization of equine surfactant protein A.

    Science.gov (United States)

    Hospes, R; Hospes, B I L; Reiss, I; Bostedt, H; Gortner, L

    2002-12-01

    In the following, we describe the isolation and sequencing of the equine surfactant protein A (Sp-A) as found in both the cDNA and the genomic DNA. We found a length of the cDNA sequence of 747 bp (base pairs), in translation into amino acids of 248. Compared with the known molecular biological facts about Sp-A in other species, the cDNA sequence obtained showed highest homology with that of sheep (85.01%). The genomic DNA of equine Sp-A, as in other species, includes three introns. There were no hints for the existence of two different Sp-A genes. These results should form the basis for a better understanding of respiratory failure in foals and adult horses, and also lead to further studies on this item.

  16. Nonlinear surface dilatational rheology and foaming behavior of protein and protein fibrillar aggregates in the presence of natural surfactant

    NARCIS (Netherlands)

    Wan, Zhili; Yang, Xiaoquan; Sagis, L.M.C.

    2016-01-01

    The surface and foaming properties of native soy glycinin (11S) and its heat-induced fibrillar aggregates, in the presence of natural surfactant steviol glycoside (STE), were investigated and compared at pH 7.0 to determine the impact of protein structure modification on protein?surfactant interfaci

  17. Fluidizing and Solidifying Effects of Perfluorooctylated Fatty Alcohols on Pulmonary Surfactant Monolayers.

    Science.gov (United States)

    Nakahara, Hiromichi

    2016-01-01

    Pulmonary surfactant (PS) preparations based mainly on bovine or porcine extracts are commonly administered to patients with neonatal respiratory distress syndrome (NRDS) for therapy. The preparations are sufficiently effective to treat NRDS; however, they are associated with a risk of infection and involve costly purification procedures to achieve batch-to-batch reproducibility. Therefore, we investigated the mechanism and interfacial behavior of synthetic PS preparations containing a mimicking peptide (KLLKLLLKLWLKLLKLLL, Hel 13-5). In particular, a hybrid PS formulation with fluorinated amphiphiles is reported from the perspective of surface chemistry. Fluorinated amphiphiles are characterized by exceptional chemical and biological inertness, high oxygen-dissolving capacity, low surface tension, excellent spreading ability, and high fluidity. These properties are superior to those for the corresponding hydrocarbon analogs. Indeed, a small amount of fluorinated long-chain alcohols enhances the effectiveness of the model PS preparation for in vitro pulmonary functions. Moreover, the mode of the improved efficacy differs depending on the hydrophobic chain length in the alcohols. For alcohols with a short fluorocarbon (FC) chain, the monolayer phase of the model PS preparation remains disordered (fluidization). However, the addition of alcohols containing a long FC chain reduces the disordered/ordered phase transition pressure and the growth of ordered domains of the monolayer (condensation). Furthermore, repeated compression-expansion isotherms of the monolayers, which can simulate respiration in the lung, suggest irreversible elimination of the short-FC alcohol into the subphase and enhancement of the squeeze-out phenomenon of certain PS components by solid-like monolayer formation induced by the long-FC alcohol. We demonstrated that fluorinated amphiphiles may be used as additives for synthetic or commercial PS preparations for RDS treatment.

  18. Pulmonary surfactant augments cytotoxicity of silica nanoparticles: Studies on an in vitro air–blood barrier model

    Directory of Open Access Journals (Sweden)

    Jennifer Y. Kasper

    2015-02-01

    Full Text Available The air–blood barrier is a very thin membrane of about 2.2 µm thickness and therefore represents an ideal portal of entry for nanoparticles to be used therapeutically in a regenerative medicine strategy. Until now, numerous studies using cellular airway models have been conducted in vitro in order to investigate the potential hazard of NPs. However, in most in vitro studies a crucial alveolar component has been neglected. Before aspirated NPs encounter the cellular air–blood barrier, they impinge on the alveolar surfactant layer (10–20 nm in thickness that lines the entire alveolar surface. Thus, a prior interaction of NPs with pulmonary surfactant components will occur. In the present study we explored the impact of pulmonary surfactant on the cytotoxic potential of amorphous silica nanoparticles (aSNPs using in vitro mono- and complex coculture models of the air–blood barrier. Furthermore, different surface functionalisations (plain-unmodified, amino, carboxylate of the aSNPs were compared in order to study the impact of chemical surface properties on aSNP cytotoxicity in combination with lung surfactant. The alveolar epithelial cell line A549 was used in mono- and in coculture with the microvascular cell line ISO-HAS-1 in the form of different cytotoxicity assays (viability, membrane integrity, inflammatory responses such as IL-8 release. At a distinct concentration (100 µg/mL aSNP–plain displayed the highest cytotoxicity and IL-8 release in monocultures of A549. aSNP–NH2 caused a slight toxic effect, whereas aSNP–COOH did not exhibit any cytotoxicity. In combination with lung surfactant, aSNP–plain revealed an increased cytotoxicity in monocultures of A549, aSNP–NH2 caused a slightly augmented toxic effect, whereas aSNP–COOH did not show any toxic alterations. A549 in coculture did not show any decreased toxicity (membrane integrity for aSNP–plain in combination with lung surfactant. However, a significant augmented

  19. "SP-G", a putative new surfactant protein--tissue localization and 3D structure.

    Directory of Open Access Journals (Sweden)

    Felix Rausch

    Full Text Available Surfactant proteins (SP are well known from human lung. These proteins assist the formation of a monolayer of surface-active phospholipids at the liquid-air interface of the alveolar lining, play a major role in lowering the surface tension of interfaces, and have functions in innate and adaptive immune defense. During recent years it became obvious that SPs are also part of other tissues and fluids such as tear fluid, gingiva, saliva, the nasolacrimal system, and kidney. Recently, a putative new surfactant protein (SFTA2 or SP-G was identified, which has no sequence or structural identity to the already know surfactant proteins. In this work, computational chemistry and molecular-biological methods were combined to localize and characterize SP-G. With the help of a protein structure model, specific antibodies were obtained which allowed the detection of SP-G not only on mRNA but also on protein level. The localization of this protein in different human tissues, sequence based prediction tools for posttranslational modifications and molecular dynamic simulations reveal that SP-G has physicochemical properties similar to the already known surfactant proteins B and C. This includes also the possibility of interactions with lipid systems and with that, a potential surface-regulatory feature of SP-G. In conclusion, the results indicate SP-G as a new surfactant protein which represents an until now unknown surfactant protein class.

  20. Effects of surfactant depletion on regional pulmonary metabolic activity during mechanical ventilation.

    Science.gov (United States)

    de Prost, Nicolas; Costa, Eduardo L; Wellman, Tyler; Musch, Guido; Winkler, Tilo; Tucci, Mauro R; Harris, R Scott; Venegas, Jose G; Vidal Melo, Marcos F

    2011-11-01

    Inflammation during mechanical ventilation is thought to depend on regional mechanical stress. This can be produced by concentration of stresses and cyclic recruitment in low-aeration dependent lung. Positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG) allows for noninvasive assessment of regional metabolic activity, an index of neutrophilic inflammation. We tested the hypothesis that, during mechanical ventilation, surfactant-depleted low-aeration lung regions present increased regional (18)F-FDG uptake suggestive of in vivo increased regional metabolic activity and inflammation. Sheep underwent unilateral saline lung lavage and were ventilated supine for 4 h (positive end-expiratory pressure = 10 cmH(2)O, tidal volume adjusted to plateau pressure = 30 cmH(2)O). We used PET scans of injected (13)N-nitrogen to compute regional perfusion and ventilation and injected (18)F-FDG to calculate (18)F-FDG uptake rate. Regional aeration was quantified with transmission scans. Whole lung (18)F-FDG uptake was approximately two times higher in lavaged than in nonlavaged lungs (2.9 ± 0.6 vs. 1.5 ± 0.3 10(-3)/min; P < 0.05). The increased (18)F-FDG uptake was topographically heterogeneous and highest in dependent low-aeration regions (gas fraction 10-50%, P < 0.001), even after correction for lung density and wet-to-dry lung ratios. (18)F-FDG uptake in low-aeration regions of lavaged lungs was higher than that in low-aeration regions of nonlavaged lungs (P < 0.05). This occurred despite lower perfusion and ventilation to dependent regions in lavaged than nonlavaged lungs (P < 0.001). In contrast, (18)F-FDG uptake in normally aerated regions was low and similar between lungs. Surfactant depletion produces increased and heterogeneously distributed pulmonary (18)F-FDG uptake after 4 h of supine mechanical ventilation. Metabolic activity is highest in poorly aerated dependent regions, suggesting local increased inflammation.

  1. Donor surfactant protein D (SP-D) polymorphisms are associated with lung transplant outcome.

    Science.gov (United States)

    Aramini, B; Kim, C; Diangelo, S; Petersen, E; Lederer, D J; Shah, L; Robbins, H; Floros, J; Arcasoy, S M; Sonett, J R; D'Ovidio, F

    2013-08-01

    Chronic lung allograft dysfunction (CLAD) is the major factor limiting long-term success of lung transplantation. Polymorphisms of surfactant protein D (SP-D), an important molecule within lung innate immunity, have been associated with various lung diseases. We investigated the association between donor lung SP-D polymorphisms and posttransplant CLAD and survival in 191 lung transplant recipients consecutively transplanted. Recipients were prospectively followed with routine pulmonary function tests. Donor DNA was assayed by pyrosequencing for SP-D polymorphisms of two single-nucleotide variations altering amino acids in the mature protein N-terminal domain codon 11 (Met(11) Thr), and in codon 160 (Ala(160) Thr) of the C-terminal domain. CLAD was diagnosed in 88/191 patients, and 60/191 patients have died. Recipients of allografts that expressed the homozygous Met(11) Met variant of aa11 had significantly greater freedom from CLAD development and better survival compared to those with the homozygous Thr(11) Th variant of aa11. No significant association was noted for SP-D variants of aa160. Lung allografts with the SP-D polymorphic variant Thr(11) Th of aa11 are associated with development of CLAD and reduced survival. The observed genetic differences of the donor lung, potentially with their effects on innate immunity, may influence the clinical outcomes after lung transplantation.

  2. Interactions Between Biopolymers and Surfactants with Focus on Fluorosurfactants and Proteins

    OpenAIRE

    Macáková, Lubica

    2007-01-01

    The aim of this thesis was to obtain a better understanding of the association between surfactants and biopolymers in bulk solutions and at solid/aqueous liquid interface. In order to do this, the interactions between surfactants and biopolymers were investigated with a variety of experimental techniques. The main focus has been on the interactions between fluorosurfactants and proteins, which are important during electrophoresis of proteins in silica capillaries. Electrophoretic separation o...

  3. Interactions between Surfactants in Solution and Electrospun Protein Fibers: Effects on Release Behavior and Fiber Properties.

    Science.gov (United States)

    Stephansen, Karen; García-Díaz, María; Jessen, Flemming; Chronakis, Ioannis S; Nielsen, Hanne M

    2016-03-07

    Intermolecular interaction phenomena occurring between endogenous compounds, such as proteins and bile salts, and electrospun compounds are so far unreported, despite the exposure of fibers to such biorelevant compounds when applied for biomedical purposes, e.g., tissue engineering, wound healing, and drug delivery. In the present study, we present a systematic investigation of how surfactants and proteins, as physiologically relevant components, interact with insulin-loaded fish sarcoplasmic protein (FSP) electrospun fibers (FSP-Ins fibers) in solution and thereby affect fiber properties such as accessible surface hydrophilicity, physical stability, and release characteristics of an encapsulated drug. Interactions between insulin-loaded protein fibers and five anionic surfactants (sodium taurocholate, sodium taurodeoxycholate, sodium glycocholate, sodium glycodeoxycholate, and sodium dodecyl sulfate), a cationic surfactant (benzalkonium chloride), and a neutral surfactant (Triton X-100) were studied. The anionic surfactants increased the insulin release in a concentration-dependent manner, whereas the neutral surfactant had no significant effect on the release. Interestingly, only minute amounts of insulin were released from the fibers when benzalkonium chloride was present. The FSP-Ins fibers appeared dense after incubation with this cationic surfactant, whereas high fiber porosity was observed after incubation with anionic or neutral surfactants. Contact angle measurements and staining with the hydrophobic dye 8-anilino-1-naphthalenesulfonic acid indicated that the FSP-Ins fibers were hydrophobic, and showed that the fiber surface properties were affected differently by the surfactants. Bovine serum albumin also affected insulin release in vitro, indicating that also proteins may affect the fiber performance in an in vivo setting.

  4. Study of the interactions between lysozyme and a fully-fluorinated surfactant in aqueous solution at different surfactant-protein ratios.

    Science.gov (United States)

    Ruso, Juan M; González-Pérez, Alfredo; Prieto, Gerardo; Sarmiento, Félix

    2003-11-01

    The interactions of a fluorinated surfactant, sodium perfluorooctanoate, with lysozyme, have been investigated by a combination of UV absorbance, electrical conductivity and dynamic light scattering to detect and to characterize the conformational transitions of lysozyme. By using difference spectroscopy, the transition was followed as a function of surfactant concentration, and the data were analyzed to obtain the Gibbs energy of the transition in water (DeltaGw(o)) and in a hydrophobic environment (DeltaGh(o)) for saturated protein-surfactant complexes. Electrical conductivity was used to determine the critical micelle concentration of the surfactant in the presence of different lysozyme concentration. From these results, the average number of surfactant monomer per protein molecule was calculated. Finally, dynamic light scattering show that only changes in the secondary structure of the protein can be observed.

  5. The SARS coronavirus spike glycoprotein is selectively recognized by lung surfactant protein D and activates macrophages

    DEFF Research Database (Denmark)

    Leth-Larsen, Rikke; Zhong, Fei; Chow, Vincent T K;

    2007-01-01

    Da glycosylated protein. It was not secreted in the presence of tunicamycin and was detected as a 130 kDa protein in the cell lysate. The purified S-protein bound to Vero but not 293T cells and was itself recognized by lung surfactant protein D (SP-D), a collectin found in the lung alveoli. The binding required...

  6. Effect of pulmonary surfactant combined with mucosolvan on immune function, liver and kidney function in neonatal respiratory distress syndrome

    Institute of Scientific and Technical Information of China (English)

    Juan Ma; Xiao-Lei Wang; Zheng-Ying Li; Tao-Ying Chen

    2016-01-01

    Objective:To explore the pulmonary surfactant combined with mucosolvan on immune function, liver and kidney function in neonatal respiratory distress syndrome, provide help for the treatment.Methods:A total of 160 cases of neonatal respiratory distress syndrome in our hospital were selected and randomly divided into observation group and control group according to the random number table method, 80 cases in each group, the control group was given conventional therapy, the observation group was given pulmonary surfactant combined with mucosolvan treatment on the basis of conventional therapy, before treatment and 3 days after treatment, the arterial blood gas correlation indexes, respiratory distress syndrome related factors, immune related factors, liver and kidney function indexes were detected in the 2 groups.Results:Compared with before treatment, in the observation group and the control group after treatment, arterial blood gas indexes PaO2, TCO2, SaO2 significantly increased, while PaCO2 significantly decreased, related cytokines KL-6, MIF-1 and HMGB-1 significantly decreased, immunologic factors IFN-γ and IL-4 significantly increased, while IL-10 and TNF-α significantly decreased, liver function indexes AST, ALT and renal function indexes BUN, CRE decreased significantly, the differences had statistically significant; compared with the control group after treatment, in the observation group after combined treatment, arterial blood gas indexes PaO2, TCO2, SaO2 significantly increased, PaCO2 significantly decreased, related cytokines KL-6, MIF-1 and HMGB-1 significantly decreased, immunologic factors IL-10 and IL-4 significantly increased, IFN-γ and TNF-α significantly decreased, liver function indexes AST, ALT and renal function indexes BUN, CRE decreased significantly; the differences had statistically significant.Conclusion:Pulmonary surfactant combined with mucosolvan can improve the respiratory distress syndrome related factors, immune function, liver

  7. How Chain Length and Charge Affect Surfactant Denaturation of Acyl Coenzyme A Binding Protein (ACBP)

    DEFF Research Database (Denmark)

    Andersen, Kell Kleiner; Otzen, Daniel

    2009-01-01

    Using intrinsic tryptophan fluorescence, equilibria and kinetics of unfolding of acyl coenzyme A binding protein (ACBP) have been investigated in sodium alkyl sulfate surfactants of different chain length (8-16 carbon atoms) and with different proportions of the nonionic surfactant dodecyl...... maltoside (DDM). The aim has been to determine how surfactant chain length and micellar charge affect the denaturation mechanism. ACBP denatures in two steps irrespective of surfactant chain length, but with increasing chain length, the potency of the denaturant rises more rapidly than the critical micelle...... constants increases linearly with denaturant concentration below the cmc but declines at higher concentrations. Both shortening chain length and decreasing micellar charge reduce the overall kinetics of unfolding and makes the dependence of unfolding rate constants on surfactant concentration more complex...

  8. Natural history of five children with surfactant protein C mutations and interstitial lung disease.

    Science.gov (United States)

    Avital, Avraham; Hevroni, Avigdor; Godfrey, Simon; Cohen, Shlomo; Maayan, Channa; Nusair, Samir; Nogee, Lawrence M; Springer, Chaim

    2014-11-01

    Interstitial lung diseases in infants and children are uncommon and may be caused by specific inborn errors of surfactant metabolism. Five children with open lung biopsy diagnosed interstitial lung disease were followed (mean of 27.2 years) and evaluated for surfactant protein gene mutations. Four of the children were originally diagnosed as desquamative interstitial pneumonitis and one as chronic interstitial pneumonitis. All had good response to chloroquine or hydroxychloroquine treatment for periods of 7-38 months. Lung function tests, incremental exercise tests, and rentgenological studies were performed in the children. Surfactant protein gene mutations were searched in all the patients and in part of their families. Three of the patients, aged now 32, 29, and 37 years, feel well and have normal lung function, while two of the patients, both females, aged 28 and 37 years, conduct normal activities of daily living, have healthy children but have clinical, physiological and rentgenological evidence of restrictive lung disease. All five patients were found to have surfactant protein C gene (SFTPC) mutations, three of them with the most common mutation (p.I73T) and the other two with new mutations of surfactant protein C gene (p.I38F and p.V39L). We conclude that detection of surfactant protein mutations should be attempted in all children presenting with interstitial lung disease. Furthermore, treatment with hydroxychloroquine should be considered in children with SFTPC mutations. Prospective evaluation of hydroxychloroquine therapy in a greater number of patients is needed.

  9. Characteristics of sugar surfactants in stabilizing proteins during freeze-thawing and freeze-drying.

    Science.gov (United States)

    Imamura, Koreyoshi; Murai, Katsuyuki; Korehisa, Tamayo; Shimizu, Noriyuki; Yamahira, Ryo; Matsuura, Tsutashi; Tada, Hiroko; Imanaka, Hiroyuki; Ishida, Naoyuki; Nakanishi, Kazuhiro

    2014-06-01

    Sugar surfactants with different alkyl chain lengths and sugar head groups were compared for their protein-stabilizing effect during freeze-thawing and freeze-drying. Six enzymes, different in terms of tolerance against inactivation because of freeze-thawing and freeze-drying, were used as model proteins. The enzyme activities that remained after freeze-thawing and freeze-drying in the presence of a sugar surfactant were measured for different types and concentrations of sugar surfactants. Sugar surfactants stabilized all of the tested enzymes both during freeze-thawing and freeze-drying, and a one or two order higher amount of added sugar surfactant was required for achieving protein stabilization during freeze-drying than for the cryoprotection. The comprehensive comparison showed that the C10-C12 esters of sucrose or trehalose were the most effective through the freeze-drying process: the remaining enzyme activities after freeze-thawing and freeze-drying increased at the sugar ester concentrations of 1-10 and 10-100 μM, respectively, and increased to a greater extent than for the other surfactants at higher concentrations. Results also indicate that, when a decent amount of sugar was also added, the protein-stabilizing effect of a small amount of sugar ester through the freeze-drying process could be enhanced. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  10. Essential Regulation of Lung Surfactant Homeostasis by the Orphan G-protein Coupled Receptor GPR116

    OpenAIRE

    Mi Young Yang; Mary Beth Hilton; Steven Seaman; Diana C. Haines; Kunio Nagashima; Christina M. Burks; Lino Tessarollo; Pavlina T. Ivanova; H. Alex Brown; Todd M. Umstead; Joanna Floros; Zissis C. Chroneos; Brad St. Croix

    2013-01-01

    GPR116 is an orphan seven-pass transmembrane receptor whose function has been unclear. Global disruption of the Gpr116 gene in mice revealed an unexpected, critical role for this receptor in lung surfactant homeostasis, resulting in progressive accumulation of surfactant lipids and proteins in the alveolar space, labored breathing, and a reduced lifespan. GPR116 expression analysis, bone marrow transplantation studies, and characterization of conditional knockout mice revealed that GPR116 exp...

  11. 肺表面活性蛋白基因突变相关性婴幼儿肺间质疾病一例报告并文献复习%Pulmonary surfactant protein gene mutation associated with pediatric interstitial lung disease: a case study and the review of related literature

    Institute of Scientific and Technical Information of China (English)

    朱春梅; 曹玲; 黄荣妍; 王亚军; 邹继珍; 袁新宇; 宋昉; 陈慧中

    2013-01-01

    目的 报告1例肺表面活性蛋白(SP)基因突变相关性婴幼儿肺间质疾病的临床诊断过程,复习文献,了解SP基因突变与婴幼儿肺间质疾病的关系.方法 总结、分析病例的临床、胸部影像学、肺活检病理资料及基因检测资料并进行相关文献复习.结果 (1)病例资料:2岁女童因呼吸急促,咳嗽、咳痰,进行性加重3月余入院,既往体健.入院体检:呼吸60次/min,口周略紫绀,三凹征(+),两肺底可闻及细湿啰音,未见杵状指、趾.病原学检查均阴性,多次血气分析提示低氧血症,胸部高分辨CT提示双肺野磨玻璃密度影,双肺野内见弥漫斑片、索条影.入院后经抗感染、抗炎治疗,临床无好转,胸部CT无改变,行胸腔镜下肺活检术,肺组织病理符合慢性间质性肺炎伴部分纤维化.SP相关基因检测提示:SP-A1基因R219W突变,SP-C基因S186N突变.(2)复习文献:1篇文献报道成人特发性肺纤维化患者携带SP-A1基因R219W突变,无相关儿童病例报告;17例SP-C基因突变婴幼儿肺间质疾病患儿资料显示:临床表现主要为呼吸急促,呼吸困难,影像学多表现为弥漫性肺部浸润,肺组织病理改变主要为非特异性间质性肺炎,检测到17种SP-C基因突变.所报病例SP-A1基因突变与成年人特发性肺纤维化患者SP-A1基因突变一致;SP-C基因S186N突变,在已发表婴幼儿SP-C突变病例中尚未见报告.结论 (1)初步诊断1例与SP-C基因S186N突变相关性婴幼儿肺间质疾病.(2) SP-C基因突变与部分婴幼儿肺间质疾病发病密切相关.%Objective To report a case of pulmonary surfactant protein (SP) gene mutation associated with pediatric interstitial lung disease,and study the clinical diagnosis process and review of related literature,to understand the relationship between interstitial lung disease and SP gene mutation in infants and children.Method The clinical,radiological,histological,and genetic testing information

  12. Surfactant Protein-A inhibits Aspergillus fumigatus-induced allergic T-cell responses

    Directory of Open Access Journals (Sweden)

    Russo Scott J

    2005-08-01

    Full Text Available Abstract Background The pulmonary surfactant protein (SP-A has potent immunomodulatory activities but its role and regulation during allergic airway inflammation is unknown. Methods We studied changes in SP-A expression in the bronchoalveolar lavage (BAL using a murine model of single Aspergillus fumigatus (Af challenge of sensitized animals. Results SP-A protein levels in the BAL fluid showed a rapid, transient decline that reached the lowest values (25% of controls 12 h after intranasal Af provocation of sensitized mice. Decrease of SP-A was associated with influx of inflammatory cells and increase of IL-4 and IL-5 mRNA and protein levels. Since levels of SP-A showed a significant negative correlation with these BAL cytokines (but not with IFN-γ, we hypothesized that SP-A exerts an inhibitory effect on Th2-type immune responses. To study this hypothesis, we used an in vitro Af-rechallenge model. Af-induced lymphocyte proliferation of cells isolated from sensitized mice was inhibited in a dose-dependent manner by addition of purified human SP-A (0.1–10 μg/ml. Flow cytometric studies on Af-stimulated lymphocytes indicated that the numbers of CD4+ (but not CD8+ T cells were significantly increased in the parental population and decreased in the third and fourth generation in the presence of SP-A. Further, addition of SP-A to the tissue culture inhibited Af-induced IL-4 and IL-5 production suggesting that SP-A directly suppressed allergen-stimulated CD4+ T cell function. Conclusion We speculate that a transient lack of this lung collectin following allergen exposure of the airways may significantly contribute to the development of a T-cell dependent allergic immune response.

  13. Use of Viscosity to Probe the Interaction of Anionic Surfactants with a Coagulant Protein from Moringa oleifera Seeds

    Directory of Open Access Journals (Sweden)

    Raymond Maikokera

    2009-01-01

    Full Text Available The intrinsic viscosity of the coagulant protein was evaluated from the flow times of the protein solutions through a capillary viscometer, and the results suggested the coagulant protein to be globular. The interactions of the coagulant protein with anionic surfactant sodium dodecyl sulphate (SDS and sodium dodecyl benzene sulfonate (SDBS were also investigated by capillary viscometry. We conclude that there is strong protein-surfactant interaction at very low surfactant concentrations, and the behavior of the anionic surfactants in solutions containing coagulant protein is very similar. The viscometry results of protein-SDS system are compared with surface tension, fluorescence, and circular dichroism reported earlier. Combining the results of the four studies, the four approaches seem to confirm the same picture of the coagulant protein-SDS interaction. All the physical quantities when studied as function of surfactant concentration for 0.05% (w/v protein solution either exhibited a maximum or minimum at a critical SDS concentration.

  14. Meckel-Gruber syndrome protein MKS3 is required for endoplasmic reticulum-associated degradation of surfactant protein C.

    Science.gov (United States)

    Wang, Mei; Bridges, James P; Na, Cheng-Lun; Xu, Yan; Weaver, Timothy E

    2009-11-27

    Autosomal dominant mutations in the SFTPC gene are associated with idiopathic pulmonary fibrosis, a progressive lethal interstitial lung disease. Mutations that cause misfolding of the encoded proprotein surfactant protein C (SP-C) trigger endoplasmic reticulum (ER)-associated degradation, a pathway that segregates terminally misfolded substrate for retrotranslocation to the cytosol and degradation by proteasome. Microarray screens for genes involved in SP-C ER-associated degradation identified MKS3/TMEM67, a locus previously linked to the ciliopathy Meckel-Gruber syndrome. In this study, MKS3 was identified as a membrane glycoprotein predominantly localized to the ER. Expression of MKS3 was up-regulated by genetic or pharmacological inducers of ER stress. The ER lumenal domain of MKS3 interacted with a complex that included mutant SP-C and associated chaperones, whereas the region predicted to encode the transmembrane domains of MKS3 interacted with cytosolic p97. Deletion of the transmembrane and cytosolic domains abrogated interaction of MKS3 with p97 and resulted in accumulation of mutant SP-C proprotein; knockdown of MKS3 also inhibited degradation of mutant SP-C. These results support a model in which MKS3 links the ER lumenal quality control machinery with the cytosolic degradation apparatus.

  15. Meckel-Gruber Syndrome Protein MKS3 Is Required for Endoplasmic Reticulum-associated Degradation of Surfactant Protein C*

    Science.gov (United States)

    Wang, Mei; Bridges, James P.; Na, Cheng-Lun; Xu, Yan; Weaver, Timothy E.

    2009-01-01

    Autosomal dominant mutations in the SFTPC gene are associated with idiopathic pulmonary fibrosis, a progressive lethal interstitial lung disease. Mutations that cause misfolding of the encoded proprotein surfactant protein C (SP-C) trigger endoplasmic reticulum (ER)-associated degradation, a pathway that segregates terminally misfolded substrate for retrotranslocation to the cytosol and degradation by proteasome. Microarray screens for genes involved in SP-C ER-associated degradation identified MKS3/TMEM67, a locus previously linked to the ciliopathy Meckel-Gruber syndrome. In this study, MKS3 was identified as a membrane glycoprotein predominantly localized to the ER. Expression of MKS3 was up-regulated by genetic or pharmacological inducers of ER stress. The ER lumenal domain of MKS3 interacted with a complex that included mutant SP-C and associated chaperones, whereas the region predicted to encode the transmembrane domains of MKS3 interacted with cytosolic p97. Deletion of the transmembrane and cytosolic domains abrogated interaction of MKS3 with p97 and resulted in accumulation of mutant SP-C proprotein; knockdown of MKS3 also inhibited degradation of mutant SP-C. These results support a model in which MKS3 links the ER lumenal quality control machinery with the cytosolic degradation apparatus. PMID:19815549

  16. Endogenous lung surfactant inspired pH responsive nanovesicle aerosols: Pulmonary compatible and site-specific drug delivery in lung metastases

    Science.gov (United States)

    Joshi, Nitin; Shirsath, Nitesh; Singh, Ankur; Joshi, Kalpana S.; Banerjee, Rinti

    2014-11-01

    Concerns related to pulmonary toxicity and non-specificity of nanoparticles have limited their clinical applications for aerosol delivery of chemotherapeutics in lung cancer. We hypothesized that pulmonary surfactant mimetic nanoparticles that offer pH responsive release specifically in tumor may be a possible solution to overcome these issues. We therefore developed lung surfactant mimetic and pH responsive lipid nanovesicles for aerosol delivery of paclitaxel in metastatic lung cancer. 100-200 nm sized nanovesicles showed improved fusogenicity and cytosolic drug release, specifically with cancer cells, thereby resulting in improved cytotoxicity of paclitaxel in B16F10 murine melanoma cells and cytocompatibility with normal lung fibroblasts (MRC 5). The nanovesicles showed airway patency similar to that of endogenous pulmonary surfactant and did not elicit inflammatory response in alveolar macrophages. Their aerosol administration while significantly improving the biodistribution of paclitaxel in comparison to Taxol (i.v.), also showed significantly higher metastastes inhibition (~75%) in comparison to that of i.v. Taxol and i.v. Abraxane. No signs of interstitial pulmonary fiborisis, chronic inflammation and any other pulmonary toxicity were observed with nanovesicle formulation. Overall, these nanovesicles may be a potential platform to efficiently deliver hydrophobic drugs as aerosol in metastatic lung cancer and other lung diseases, without causing pulmonary toxicity.

  17. On relationships between surfactant type and globular proteins interactions in solution.

    Science.gov (United States)

    Blanco, Elena; Ruso, Juan M; Prieto, Gerardo; Sarmiento, Félix

    2007-12-01

    The binding of sodium perfluorooctanoate (C8FONa), sodium octanoate (C8HONa), lithium perfluorooctanoate (C8FOLi), and sodium dodecanoate (C12HONa) onto myoglobin, ovalbumin, and catalase in water has been characterized using electrophoretic mobility. The tendency of the protein-surfactant complexes to change their charge in the order catalase < ovalbumin < myoglobin was observed which was related to the contents of alpha-helices in the proteins. alpha-Helices are more hydrophobic than beta-sheets. The effect of surfactant on the zeta potentials follows C8HONa < C8FONa < C8FOLi < C12HONa for catalase and ovalbumin; and C8HONa < C8FOLi < C8FONa < C12HONa for myoglobin. The numbers of binding sites on the proteins were determined from the observed increases of the zeta-potential as a function of surfactant concentration in the regions where the binding was a consequence of the hydrophobic effect. The Gibbs energies of binding of the surfactants onto the proteins were evaluated. For all systems, Gibbs energies are negative and large at low concentrations (where binding to the high energy sites takes place) and become less negative at higher ones. This fact suggests a saturation process. Changes in Gibbs energies with the different proteins and surfactants under study have been found to follow same sequence than that found for the charge. The role of hydrophobic interactions in these systems has been demonstrated to be the predominant.

  18. Stable intermediates determine proteins' primary unfolding sites in the presence of surfactants

    DEFF Research Database (Denmark)

    Petersen, Steen Vang; Andersen, Kell kleiner; Enghild, Jan J.

    2009-01-01

    Despite detailed knowledge of the overall structural changes and stoichiometries of surfactant binding, little is known about which protein regions constitute the preferred sites of attack for initial unfolding. Here we have exposed three proteins to limited proteolysis at anionic (SDS) and catio......Despite detailed knowledge of the overall structural changes and stoichiometries of surfactant binding, little is known about which protein regions constitute the preferred sites of attack for initial unfolding. Here we have exposed three proteins to limited proteolysis at anionic (SDS......) and cationic (DTAC) surfactant concentrations corresponding to specific conformational transitions, using the surfactant-robust broad-specificity proteases Savinase and Alcalase. Cleavage sites are identified by SDS-PAGE and N-terminal sequencing. We observe well-defined cleavage fragments, which suggest......, cleavage sites can be rationalized from the structure of the protein's folding transition state and the position of loops in the native state. Nevertheless, they are more sensitive to choice of surfactant and protease, probably reflecting a heterogeneous and fluctuating ensemble of partially unfolded...

  19. Two Mutations in Surfactant Protein C Gene Associated with Neonatal Respiratory Distress

    Directory of Open Access Journals (Sweden)

    Anna Tarocco

    2015-01-01

    Full Text Available Multiple mutations of surfactant genes causing surfactant dysfunction have been described. Surfactant protein C (SP-C deficiency is associated with variable clinical manifestations ranging from neonatal respiratory distress syndrome to lethal lung disease. We present an extremely low birth weight male infant with an unusual course of respiratory distress syndrome associated with two mutations in the SFTPC gene: C43-7G>A and 12T>A. He required mechanical ventilation for 26 days and was treated with 5 subsequent doses of surfactant with temporary and short-term efficacy. He was discharged at 37 weeks of postconceptional age without any respiratory support. During the first 16 months of life he developed five respiratory infections that did not require hospitalization. Conclusion. This mild course in our patient with two mutations is peculiar because the outcome in patients with a single SFTPC mutation is usually poor.

  20. Electrophoretic and spectroscopic characterization of the protein patterns formed in different surfactant solutions.

    Science.gov (United States)

    Blanco, Elena; Ruso, Juan M; Prieto, Gerardo; Sarmiento, Félix

    2008-01-01

    The complexations between catalase and the sodium perfluorooctanoate/sodium octanoate and sodium perfluorooctanoate/sodium dodecanoate systems have been studied by a combination of electrophoresis and spectroscopy measurements. The numbers of adsorption sites on the protein were determined from the observed increases of the zeta-potential as a function of surfactant concentration in the regions where the adsorption was a consequence of the hydrophobic effect. The Gibbs energies of adsorption of the surfactants onto the protein were evaluated and the results show that for all systems, Gibbs energies are negative and larger, in absolute values, at low values of surfactant concentration where binding to the high energy sites takes place, and become less negative as more surfactant molecules bind, suggesting a saturation process. The role of hydrophobic interactions in these systems has been demonstrated to be the predominant. Spectroscopy measurements suggest conformational changes on catalase depending on the surfactant mixture as well as the mixed ratio. No isosbestic point or shifts have been found showing that catalase has spectrophotometrically one kind of binding site for these surfactant mixtures.

  1. OSCAR Is a Receptor for Surfactant Protein D That Activates TNF-α Release from Human CCR2+ Inflammatory Monocytes

    DEFF Research Database (Denmark)

    Barrow, Alexander D; Palarasah, Yaseelan; Bugatti, Mattia;

    2015-01-01

    Surfactant protein D (SP-D) is critical for maintenance of lung homeostasis and provides a first line of defense to pathogens at mucosal surfaces. Polymorphisms in the SP-D-encoding gene SFTPD have been associated with chronic obstructive pulmonary disease and ulcerative colitis. Identification...... of recombinant SP-D and captured native SP-D from human bronchoalveolar lavage. OSCAR localized in an intracellular compartment of alveolar macrophages together with SP-D. Moreover, we found OSCAR on the surface of interstitial lung and blood CCR2(+) inflammatory monocytes, which secreted TNF-α when exposed...... therapeutic target in chronic inflammatory diseases of the lung as well as other diseases involving tissue accumulation of SP-D, infiltration of inflammatory monocytes, and release of TNF-α....

  2. Species Differences in the Carbohydrate Binding Preferences of Surfactant Protein D

    DEFF Research Database (Denmark)

    Crouch, Erika C.; Smith, Kelly; McDonald, Barbara

    2006-01-01

    Interactions of surfactant protein D (SP-D) with micro-organisms and organic antigens involve binding to the trimeric neck plus carbohydrate recognition domain (neck+CRD). In these studies, we compared the ligand binding of homologous human, rat, and mouse trimeric neck+CRD fusion proteins, each ...

  3. Inherited surfactant deficiency due to uniparental disomy of rare mutations in the surfactant protein-B and ATP binding cassette, subfamily A, member 3 genes

    Science.gov (United States)

    Hamvas, Aaron; Nogee, Lawrence M.; Wegner, Daniel J.; DePass, Kelcey; Christodoulou, John; Bennetts, Bruce; McQuade, Leon R.; Gray, Peter H.; Deterding, Robin R.; Carroll, Travis R.; Kammesheidt, Anja; Kasch, Laura M.; Kulkarni, Shashikant; Cole, F. Sessions

    2009-01-01

    Objective To characterize inheritance of homozygous, rare, recessive loss-of-function mutations in the surfactant protein-B (SFTPB) or ATP binding cassette, subfamily A, member 3 (ABCA3) genes in newborns with lethal respiratory failure. Study design We resequenced parents whose infants were homozygous for mutations in SFTPB or ABCA3. For infants with only one heterozygous parent, we performed microsatellite analysis for chromosomes 2 (SFTPB) and 16 (ABCA3). Results We identified one infant homozygous for the c.1549C>GAA mutation (121ins2) in SFTPB for whom only the mother was heterozygous and 3 infants homozygous for mutations in ABCA3 (p.K914R, p.P147L, and c.806_7insGCT) for whom only the fathers were heterozygous. For the SP-B deficient infant, microsatellite markers confirmed maternal heterodisomy with segmental isodisomy. Microsatellite analysis confirmed paternal isodisomy for the three ABCA3 deficient infants. Two ABCA3 deficient infants underwent lung transplantation at 3 and 5 months of age, respectively, and two infants died. None exhibited any non-pulmonary phenotype. Conclusions Uniparental disomy should be suspected in infants with rare homozygous mutations in SFTPB or ABCA3. Confirmation of parental carrier status is important to provide recurrence risk and to monitor expression of other phenotypes that may emerge through reduction to homozygosity of recessive alleles. PMID:19647838

  4. The Effect of Membrane Environment on Surfactant Protein C Stability Studied by Constant-pH Molecular Dynamics.

    Science.gov (United States)

    Carvalheda, Catarina A; Campos, Sara R R; Baptista, António M

    2015-10-26

    Pulmonary surfactant protein C (SP-C) is a small peptide with two covalently linked fatty acyl chains that plays a crucial role in the formation and stabilization of the pulmonary surfactant reservoirs during the compression and expansion steps of the respiratory cycle. Although its function is known to be tightly related to its highly hydrophobic character and key interactions maintained with specific lipid components, much is left to understand about its molecular mechanism of action. Also, although it adopts a mainly helical structure while associated with the membrane, factors as pH variation and deacylation have been shown to affect its stability and function. In this work, the conformational behavior of both the acylated and deacylated SP-C isoforms was studied in a DPPC bilayer under different pH conditions using constant-pH molecular dynamics simulations. Our findings show that both protein isoforms are remarkably stable over the studied pH range, even though the acylated isoform exhibits a labile helix-turn-helix motif rarely observed in the other isoform. We estimate similar tilt angles for the two isoforms over the studied pH range, with a generally higher degree of internalization of the basic N-terminal residues in the deacylated case, and observe and discuss some protonation-conformation coupling effects. Both isoforms establish contacts with the surrounding lipid molecules (preferentially with the sn-2 ester bonds) and have a local effect on the conformational behavior of the surrounding lipid molecules, the latter being more pronounced for acylated SP-C.

  5. Anionic surfactants enhance click reaction-mediated protein conjugation with ubiquitin.

    Science.gov (United States)

    Schneider, Daniel; Schneider, Tatjana; Aschenbrenner, Joos; Mortensen, Franziska; Scheffner, Martin; Marx, Andreas

    2016-03-01

    The Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) has become increasingly important in the conjugation chemistry of biomolecules. For example, it is an efficient and convenient method to generate defined ubiquitin-protein conjugates. Here, we investigate the effect of surfactants on the efficiency of CuAAC for chemical protein ubiquitylation. We found that anionic surfactants enhance conjugate formation by up to 10-fold resulting in high yields even at low (i.e., micromolar) concentrations of the reactants. Notably, the herein investigated conjugates are functional and thus properly folded. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. The structure of latherin, a surfactant allergen protein from horse sweat and saliva.

    Science.gov (United States)

    Vance, Steven J; McDonald, Rhona E; Cooper, Alan; Smith, Brian O; Kennedy, Malcolm W

    2013-08-06

    Latherin is a highly surface-active allergen protein found in the sweat and saliva of horses and other equids. Its surfactant activity is intrinsic to the protein in its native form, and is manifest without associated lipids or glycosylation. Latherin probably functions as a wetting agent in evaporative cooling in horses, but it may also assist in mastication of fibrous food as well as inhibition of microbial biofilms. It is a member of the PLUNC family of proteins abundant in the oral cavity and saliva of mammals, one of which has also been shown to be a surfactant and capable of disrupting microbial biofilms. How these proteins work as surfactants while remaining soluble and cell membrane-compatible is not known. Nor have their structures previously been reported. We have used protein nuclear magnetic resonance spectroscopy to determine the conformation and dynamics of latherin in aqueous solution. The protein is a monomer in solution with a slightly curved cylindrical structure exhibiting a 'super-roll' motif comprising a four-stranded anti-parallel β-sheet and two opposing α-helices which twist along the long axis of the cylinder. One end of the molecule has prominent, flexible loops that contain a number of apolar amino acid side chains. This, together with previous biophysical observations, leads us to a plausible mechanism for surfactant activity in which the molecule is first localized to the non-polar interface via these loops, and then unfolds and flattens to expose its hydrophobic interior to the air or non-polar surface. Intrinsically surface-active proteins are relatively rare in nature, and this is the first structure of such a protein from mammals to be reported. Both its conformation and proposed method of action are different from other, non-mammalian surfactant proteins investigated so far.

  7. 肺泡表面相关蛋白A、D与结核分枝杆菌感染相关性的研究进展%Research progress of correlation between pulmonary surfactant associated protein A, D and Mycobacterium tuberculosis infection

    Institute of Scientific and Technical Information of China (English)

    胡华; 迟晶宇

    2010-01-01

    Pulmonary surfactants are synthesized and secreted by alveolar epithelial cells and bronchial epithelial cells,including SPA,SP-B,SP-C,SP-D,etc.. They play an important role in immune regulation and inflammatory response of the lung, among of which, SP-A and SP-D are the most important. Pulmonary tuberculosis is a state that allergic reaction and immune reaction exist at the same time induced by Mycobacterium tuberculosis. Mycobacterium tuberculosis goes through the respiratory tract before invading alveolous,and is phagocytized by alveolar macrophages. Pulmonary surfactants play an important intermediary role between Mycobacterium tuberculosis and alveolar macrophages. SP-A can recognize the receptors or other sugar moleculars on the cell wall of Mycobacterium tuberculosis. SP-D can bind with lipoarabinomannan on the surface of Mycobacterium tuberculosis. They are regulated and limited by certain factors in mediating the adhesion of Mycobacterium tuberculosis and alveolar macrophages, finally decide the degree of adhesion between Mycobacterium tuberculosis and alveolar macrophages, and determine the proliferation or degradation of Mycobacterium tuberculosis after entering into the body.%肺泡表面活性物质是由肺泡上皮细胞及支气管上皮细胞产生和分泌的,主要分为SP-A、SP-B、SP-C、SP-D等,在肺内免疫调节及炎症反应方面有重要作用,其中最主要的是SP-A和SP-D.肺结核是机体对结核分枝杆菌侵犯所产生的一种变态和免疫反应同时存在的状态,结核分枝杆菌在侵入肺泡之前首先要经呼吸道,被肺泡巨噬细胞吞噬,而肺泡表面活性物质在结核分枝杆菌与肺泡巨噬细胞之间起着重要中介体的作用.SP-A能够识别结核分枝杆菌细胞壁上的受体或者其他糖类分子,SP-D可以与结核分枝杆菌表面的脂质阿拉伯甘露聚糖结合,它们在介导结核分枝杆菌与肺泡巨噬细胞的黏附时受到一定因素的调节及限制,最终决

  8. Club cell protein 16 as a biomarker in pulmonary contusion

    OpenAIRE

    Wu, Feng; Ding, Boying; Yang, Xiaolong; Ma, Dongchun; Zhang, Chaodong; Hua, Congshu

    2016-01-01

    The aim of the present study was to investigate the variation and clinical significance of the 16-kDa club cell protein (CC16) in patients with pulmonary contusion. A total of 42 patients with pulmonary contusion were divided into experimental groups I (n=24, moderate pulmonary contusion) and II (n=18, severe pulmonary contusion). An enzyme-linked immunosorbent assay was used to detect the serum levels of CC16 in the two groups of patients within 24 h after the incident and at days 1, 3, 7 an...

  9. Disaturated-phosphatidylcholine and Surfactant protein-B turnover in human acute lung injury and in control patients

    Directory of Open Access Journals (Sweden)

    Rizzi Sabina

    2011-03-01

    Full Text Available Abstract Background Patients with Adult Respiratory Distress Syndrome (ARDS and Acute Lung Injury (ALI have low concentrations of disaturated-phosphatidylcholine and surfactant protein-B in bronchoalveolar lavage fluid. No information is available on their turnover. Objectives To analyze disaturated-phosphatidylcholine and surfactant protein-B turnover in patients with ARDS/ALI and in human adults with normal lungs (controls. Methods 2H2O as precursor of disaturated-phosphatidylcholine-palmitate and 113C-Leucine as precursor of surfactant protein-B were administered intravenously to 12 patients with ARDS/ALI and to 8 controls. Disaturated-phosphatidylcholine and surfactant protein-B were isolated from serial tracheal aspirates, and their fractional synthetic rate was derived from the 2H and 13C enrichment curves, obtained by gas chromatography mass spectrometry. Disaturated-phosphatidylcholine, surfactant protein-B, and protein concentrations in tracheal aspirates were also measured. Results 1 Surfactant protein-B turned over at faster rate than disaturated-phosphatidylcholine both in ARDS/ALI patients and in controls. 2 In patients with ARDS/ALI the fractional synthesis rate of disaturated-phosphatidylcholine was 3.1 times higher than in controls (p Conclusions 1 Disaturated-phosphatidylcholine and surfactant protein-B have a different turnover both in healthy and diseased lungs. 2 In ARDS/ALI the synthesis of these two surfactant components may be differently regulated.

  10. Linking surfactant protein SP-D and IL-13

    DEFF Research Database (Denmark)

    Qaseem, Asif S; Sonar, Sanchaita; Mahajan, Lakshna

    2012-01-01

    of allergen-IgE interaction, histamine release by sensitised mast cells, downregulation of specific IgE production, suppression of pulmonary and peripheral eosinophilia, inhibition of mechanisms that cause airway remodelling, and induction of apoptosis in sensitised eosinophils. SP-D can also shift helper T......-expressing IL-13 in the lung develop several characteristics of asthma such as pulmonary eosinophilia, airway epithelial hyperplasia, mucus cell metaplasia, sub-epithelial fibrosis, charcot-Leyden-Like crystals, airways obstruction, and non-specific airways hyper-responsiveness to cholinergic stimulation...

  11. Time resolved studies of interfacial reactions of ozone with pulmonary phospholipid surfactants using field induced droplet ionization mass spectrometry.

    Science.gov (United States)

    Kim, Hugh I; Kim, Hyungjun; Shin, Young Shik; Beegle, Luther W; Goddard, William A; Heath, James R; Kanik, Isik; Beauchamp, J L

    2010-07-29

    Field induced droplet ionization mass spectrometry (FIDI-MS) comprises a soft ionization method to sample ions from the surface of microliter droplets. A pulsed electric field stretches neutral droplets until they develop dual Taylor cones, emitting streams of positively and negatively charged submicrometer droplets in opposite directions, with the desired polarity being directed into a mass spectrometer for analysis. This methodology is employed to study the heterogeneous ozonolysis of 1-palmitoyl-2-oleoyl-sn-phosphatidylglycerol (POPG) at the air-liquid interface in negative ion mode using FIDI mass spectrometry. Our results demonstrate unique characteristics of the heterogeneous reactions at the air-liquid interface. We observe the hydroxyhydroperoxide and the secondary ozonide as major products of POPG ozonolysis in the FIDI-MS spectra. These products are metastable and difficult to observe in the bulk phase, using standard electrospray ionization (ESI) for mass spectrometric analysis. We also present studies of the heterogeneous ozonolysis of a mixture of saturated and unsaturated phospholipids at the air-liquid interface. A mixture of the saturated phospholipid 1,2-dipalmitoyl-sn-phosphatidylglycerol (DPPG) and unsaturated POPG is investigated in negative ion mode using FIDI-MS while a mixture of 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) and 1-stearoyl-2-oleoyl-sn-phosphatidylcholine (SOPC) surfactant is studied in positive ion mode. In both cases FIDI-MS shows the saturated and unsaturated pulmonary surfactants form a mixed interfacial layer. Only the unsaturated phospholipid reacts with ozone, forming products that are more hydrophilic than the saturated phospholipid. With extensive ozonolysis only the saturated phospholipid remains at the droplet surface. Combining these experimental observations with the results of computational analysis provides an improved understanding of the interfacial structure and chemistry of a surfactant layer system when

  12. Influence of Natural Lung Surfactant Inhalations on Clinical Symptoms and Pulmonary Function Parameters in Patients with Bronchial Asthma. Communication 1

    Directory of Open Access Journals (Sweden)

    O.V. Stepanova

    2016-12-01

    Full Text Available Background: Damage to lung surfactant (LS enabling the lung local immunity may contribute to the development of bronchial inflammation in patients with bronchial asthma. Methods and Results: A 40-day course of 16 LS (Surfactant-BL inhalations at the dose of 25mg was added to inhaled corticosteroids (ICS and short/long-acting bronchodilators or combined inhalers in 14 patients with bronchial asthma. After 7 inhalations, patients demonstrated a significant decrease in shortness of breath and bronchospasm attacks, double reduction of ICS dose (p=0.01, and improvement of pulmonary function. Forced vital capacity (FVC increases during treatment in a linear fashion (y=62.9+5.60•x; p<0.05, reaching the normal level (80% after 9 inhalations (Day 15. Forced expiratory volume (FEV1 increases in a linear fashion (y=50.7+4.15•x; p<0.05 without reaching the normal level (80% after 16 inhalations (Day 41. The FEV1/FVC ratio does not change significantly in the time period between Day 1 to Day 15. By Day 41 the value decreases significantly to 67.4±4.66% (p<0.05. The peak expiratory flow (PEF parameter increases in a linear fashion (y=53.9+5.00•x; p<0.01 from 57.7±6.33% to 76.2±9.33% of the predicted value. Conclusion: LS inhalations improve the condition of patients with BA, allow ICS dose reduction by 2 times, and improve pulmonary function parameters.

  13. 肺泡表面活性物质相关蛋白A在慢性心源性肺水肿大鼠肺组织中的表达%Expression of pulmonary surfactant associated protein A in lung tissue of rats with chronic cardiogenic pulmonary edema

    Institute of Scientific and Technical Information of China (English)

    张世魁; 杨蓉佳; 张成飞

    2013-01-01

    目的 观察慢性心源性肺水肿大鼠肺组织病理形态学改变,研究其肺泡表面活性物质相关蛋白A及肺泡灌洗液中TNF-α、IL-1、IL-6的表达,阐述它们在慢性心源性肺水肿发病机制中的作用.方法 14只自发性高血压大鼠高脂饮食饲养1年,建立慢性心源性肺水肿模型,14只血压正常大鼠以正常饮食饲养1年,为正常对照组,分别以免疫组织化学染色检测各组大鼠肺组织中SP-A的表达.RT-PCR法检测各组大鼠肺组织SP-A mRNA的表达,ELISA法检测各组大鼠支气管肺泡灌洗液中TNF-α、IL-1、IL-6的水平.结果 试验组肺组织中SP-A mRNA的表达较对照组明显上调(P<0.05),肺泡灌洗液中TNF-α、IL-1、IL-6水平明显高于对照组,差异有统计学意义(P<0.05).SP-A mRNA表达与支气管肺泡灌洗液中TNF-α、IL-1、IL-6的水平呈显著正相关(r=0.612、r=0.702、r=0.824,P<0.05).结论 慢性心源性肺水肿大鼠的肺组织中SP-A mRNA的表达较对照组明显上调,且与支气管肺泡灌洗液中TNF-α、IL-1、IL-6的水平呈显著正相关.SP-A及TNF-α、IL-1、IL-6均与慢性心源性肺水肿的发生发展过程密切相关,但因果关系不明.%Objective To observe the pathologic change of lung tissue in rats with chronic cardiogenic pulmonary edema, and to study the expression of SP-A mRNA in lung tissue and the level of TNF-α, IL-1 and IL-6 in bronchial alveolar lavage fluid in order to illustrate their pathogenesy in rats with chronic cardiogenic pulmonary edema. Methods 14 spontaneous hypertensive rats were bred with high fat diet for 1 year to set up the model of chronic cardiogenic pulmonary edema model as the test group, and 14 rats with regular blood pressure were fed with normal diet for 1 year as the control group. The expression of SP-A in lung tissue was detected by immune histo-chemical stain. The expression of SP-A mRNA in lung tissue was detected by RT-PCR. The levels of TNF-α, IL-1 and IL-6 in

  14. Stable intermediates determine proteins' primary unfolding sites in the presence of surfactants

    DEFF Research Database (Denmark)

    Petersen, Steen Vang; Andersen, Kell kleiner; Enghild, Jan J.

    2009-01-01

    Despite detailed knowledge of the overall structural changes and stoichiometries of surfactant binding, little is known about which protein regions constitute the preferred sites of attack for initial unfolding. Here we have exposed three proteins to limited proteolysis at anionic (SDS) and catio......Despite detailed knowledge of the overall structural changes and stoichiometries of surfactant binding, little is known about which protein regions constitute the preferred sites of attack for initial unfolding. Here we have exposed three proteins to limited proteolysis at anionic (SDS......) and cationic (DTAC) surfactant concentrations corresponding to specific conformational transitions, using the surfactant-robust broad-specificity proteases Savinase and Alcalase. Cleavage sites are identified by SDS-PAGE and N-terminal sequencing. We observe well-defined cleavage fragments, which suggest...... that flexibility is limited to certain regions of the protein. Cleavage sites for α-lactalbumin and myoglobin correspond to regions identified in other studies as partially unfolded at low pH or in the presence of organic solvents. For Tnfn3, which does not form partially folded structures under other conditions...

  15. A polymer surfactant corona dynamically replaces water in solvent-free protein liquids and ensures macromolecular flexibility and activity.

    Science.gov (United States)

    Gallat, François-Xavier; Brogan, Alex P S; Fichou, Yann; McGrath, Nina; Moulin, Martine; Härtlein, Michael; Combet, Jérôme; Wuttke, Joachim; Mann, Stephen; Zaccai, Giuseppe; Jackson, Colin J; Perriman, Adam W; Weik, Martin

    2012-08-15

    The observation of biological activity in solvent-free protein-polymer surfactant hybrids challenges the view of aqueous and nonaqueous solvents being unique promoters of protein dynamics linked to function. Here, we combine elastic incoherent neutron scattering and specific deuterium labeling to separately study protein and polymer motions in solvent-free hybrids. Myoglobin motions within the hybrid are found to closely resemble those of a hydrated protein, and motions of the polymer surfactant coating are similar to those of the hydration water, leading to the conclusion that the polymer surfactant coating plasticizes protein structures in a way similar to hydration water.

  16. C reactive protein and chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Dahl, Morten; Vestbo, Jørgen; Zacho, Jeppe

    2011-01-01

    It is unclear whether elevated plasma C reactive protein (CRP) is causally related to chronic obstructive pulmonary disease (COPD). The authors tested the hypothesis that genetically elevated plasma CRP causes COPD using a Mendelian randomisation design.......It is unclear whether elevated plasma C reactive protein (CRP) is causally related to chronic obstructive pulmonary disease (COPD). The authors tested the hypothesis that genetically elevated plasma CRP causes COPD using a Mendelian randomisation design....

  17. Protein denaturation due to the action of surfactants: a study by SAXS and ITC

    Energy Technology Data Exchange (ETDEWEB)

    Oseliero Filho, Pedro Leonidas; Oliveira, Cristiano Luis Pinto de [Universidade de Sao Paulo (USP), SP (Brazil); Pedersen, Jan Skov; Otzen, Daniel Erik [University of Aarhus (Denmark)

    2012-07-01

    Full text: Proteins are the major constituent of biological systems along with carbohydrates, lipids and nucleic acids (DNA and RNA). According to their structure and composition, proteins perform several functions in the organism, starting from the macroscopic level, with participation on the olfaction of animals, down to the cellular level, allocated in the membrane and making the connection between extra and intracellular environment. The function of a protein (which may be enzymatic, hormonal, structural, energetic, transport etc) is related to several factors including its structure (primary, secondary, tertiary or quaternary). Denaturation occurs when the secondary structure and/or tertiary is lost, which is almost always followed by the loss of the associated biological function. Temperature, pH and the action of surfactants influence the process of the denaturation. The influence of surfactants to the protein structure and function is the aim of this work. Therefore we are using an isolated protein, {alpha}-lactalbumin, that is found in the milk and whose function is related to the synthesis of galactose. The purpose is to characterize, in a thermodynamic-structural point of view, the denaturation of alpha-lactalbumin in the presence of surfactants anionic (sodium dodecyl sulfate - SDS), cationic (tetradecyltrimethylammonium bromide - TTAB), zwitterionic (2-diheptanoyl-sn-glycero-3- phosphocholine - DHPC) and nonionic (decyl-{beta}-D-Maltopyranoside - DM). The isothermal titration calorimetry (ITC) technique, which provides information of structural changes from changes in energy, represents the starting point for the study, while the technique of small angle X-ray scattering (SAXS) provides information about the structural characteristics of surfactant-protein complexes formed at each step of the denaturation process. The data analysis is in the initial stage, but it was possible to obtain general parameters related to the complex formed from the

  18. Circulating surfactant protein D is decreased in early rheumatoid arthritis: a 1-year prospective study

    DEFF Research Database (Denmark)

    Hoegh, S V; Lindegaard, H M; Sorensen, G L;

    2008-01-01

    Innate immune system abnormalities, e.g., mannan-binding lectin (MBL) genotype variants, have been demonstrated to modify the disease course of rheumatoid arthritis (RA). Surfactant protein D (SP-D) shares important structural and functional properties with MBL suggesting that SP-D may...... with traditional disease activity measures indicate that SP-D reflects a distinctive aspect in the RA pathogenesis....

  19. Long-term stability and circadian variation in circulating levels of surfactant protein D

    DEFF Research Database (Denmark)

    Hoegh, Silje Vermedal; Sorensen, Grith Lykke; Tornoe, Ida;

    2010-01-01

    Surfactant protein D (SP-D) is an oligomeric calcium-dependent lectin with important roles in innate host defence against infectious microorganisms. Several studies have shown that patients with inflammatory lung disease have elevated levels of circulating SP-D, and serum SP-D has been suggested ...

  20. Serum surfactant protein D is correlated to development of dementia and augmented mortality

    DEFF Research Database (Denmark)

    Nybo, Mads; Andersen, Kjeld; Sørensen, Grith Lykke;

    2007-01-01

    Development of dementia, including Alzheimer's disease (AD), is associated with lipid dysregulation and inflammation. As the host defense lectin surfactant protein D (SP-D) has multiple effects in lipid homeostasis and inflammation, the correlation between SP-D concentrations and development of d...

  1. Dynamic strength of the interaction between lung surfactant protein D (SP-D) and saccharide ligands

    DEFF Research Database (Denmark)

    Thormann, Esben; Dreyer, Jakob K; Simonsen, Adam C

    2007-01-01

    In order to investigate the dynamic strength of the interaction between lung surfactant protein D (SP-D) and different sugars, maltose, mannose, glucose, and galactose, we have used an atomic force microscope to monitor the interaction on a single molecule scale. The experiment is performed by me...

  2. 急性肺损伤/急性呼吸窘迫综合征新生儿血清Clara细胞分泌蛋白、肺表面活性蛋白A变化的意义%Significance of changes of serum Clara cell secretory protein 16, pulmonary surfactant protein A in newborn infants with acute lung injury/acute respiratory distress syndrome

    Institute of Scientific and Technical Information of China (English)

    刘改英; 林广; 刘颖; 王艳芳; 张成; 刘芳; 马海燕; 郭锐

    2013-01-01

    Objective To investigate the effect of serum Clara cell secretory protein 16 (CC16),pulmonary surfactant protein A(SP-A) in diagnosis of acute lung injury (ALI)/acute respiratory distress syndrome(ARDS) in newborn infants.Methods Fifty ALI/ARDS newborn infants in Zhuhai People's Hospital between 2011 Sep.and Dec.2012 were selected as treatment group (ALI group including 35 cases,ARDS group including 15 cases),50 healthy newborns were selected as healthy control group.The changes of serum CC16,SP-A were detected by enzyme-linked immuno sorbent assay and were compared in the 3 groups.Results 1.Serum CC16 in ALI group and ARDS group were (34.19 ± 1.09) mg/L,(55.28 ± 0.82) mg/L,respectively,which were significantly higher than that in healthy control group [(12.67 ± 1.10) mg/L] (all P < 0.05),and there was significant difference between ALI group and ARDS group(P <0.05).2.Serum SP-A in ALI group and ARDS group were(56.78 ± 3.48) mg/L,(70.23 ± 5.14) mg/L respectively,which were significantly higher than that in healthy control group [(22.10 ± 3.32) mg/L] (all P < 0.05),and there was significant difference between ALI group and ARDS group (P < 0.05).Conclusion Serum CC16,SP-A can be effective parameter for early monitoring ALI/ARDS in newborn infants.%目的 探讨血清Clara细胞分泌蛋白(CC16)、肺表面活性蛋白A(SP-A)在新生儿急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)诊断中的作用.方法 选取2011年9月至2012年12月珠海市人民医院收治的50例ALI/ARDS新生儿作为观察组,其中ALI组35例,ARDS组15例;将同期健康体检的50例新生儿作为健康对照组.采用ELISA法检测3组患儿血清CC16及SP-A水平,比较3组患儿血清CC16、SP-A水平的变化.结果 1.血清CC 16:ALI组[(34.19 ±1.09) mg/L]、ARDS组[(55.28 ±0.82) mg/L]明显高于健康对照组[(12.67±1.10)mg/L](P均<0.05),且ALI组与ARDS组比较差异亦有统计学意义(P<0.05).2.血清SP-A:ALI组[(56.78±3.48) mg

  3. The Collapse of Monolayers Containing Pulmonary Surfactant Phospholipids Is Kinetically Determined

    OpenAIRE

    Yan, Wenfei; Piknova, Barbora; Hall, Stephen B.

    2005-01-01

    Prior studies have shown that during and after slow compressions of monomolecular films containing the complete set of purified phospholipids (PPL) from calf surfactant at an air/water interface, surface pressures (π) reach and sustain values that are remarkably high relative to expectations from simple systems with model lipids. Microscopy shows that the liquid-expanded, tilted-condensed, and collapsed phases are present together in the PPL films between 45 and 65 mN/m. The Gibbs phase rule ...

  4. Nontoxic impact of PEG-coated gold nanospheres on functional pulmonary surfactant-secreting alveolar type II cells.

    Science.gov (United States)

    Bouzas, Virginia; Haller, Thomas; Hobi, Nina; Felder, Edward; Pastoriza-Santos, Isabel; Pérez-Gil, Jesús

    2014-12-01

    The outstanding properties of gold nanoparticles (NPs) make them very attractive for biomedical applications. In particular, the inhalation route has gained considerable interest as an innovative strategy for diagnosis and treatment of pulmonary diseases. It is, therefore, important to scrutinise the potentially deleterious or side effects of NPs on lung epithelium. The present study investigates, for the first time, the impact of polyethylene glycol (PEG)-coated NPs on freshly purified primary cultures of rat alveolar type II (ATII) cells. These cells play a central role in the respiratory function of the lungs. They are responsible for synthesizing and secreting pulmonary surfactant (PS), which is required to stabilise the respiratory surface during breathing dynamics. Cytotoxicity and cellular uptake of NPs was evaluated by analysing morphology, viability and exocytotic activity of ATII cells (PS secretion). The impact of ATII cells' exposure to NPs was studied in a wide range of gold concentration with particles sizes of 15 and 100 nm. The results show that PEG-coated NPs are very modestly internalised by ATII cells and it neither leads to detectable morphological changes nor to decreased cell viability nor to alterations in basic functional parameters such as PS secretion, even on exposure to high gold concentration (~0.2 mM) during relatively long periods of time (24-48 h).

  5. 慢性阻塞性肺疾病患者肺组织中肺表面活性蛋白D的表达与临床意义%Expression and clinical significance of surfactant protein D in lungs of patients of chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    陈欣; 曹洁

    2013-01-01

    目的 通过观察肺表面活性蛋白D(SP-D)在吸烟者与慢性阻塞性肺疾病(COPD)患者肺组织中的表达探究SP-D与COPD的关系.方法 通过免疫组织化学技术检测10例不吸烟非COPD、10例吸烟非COPD、10例吸烟COPD的患者的SP-D在气道上皮细胞、Ⅱ型肺泡上皮细胞和肺泡巨噬细胞的表达.结果 ①SP-D在气道上皮细胞的表达吸烟非COPD组强于COPD组(P=0.023),前两者又都强于不吸烟非COPD组(P=0.000,P=0.009);②SP-D在Ⅱ型肺泡上皮细胞的表达吸烟非COPD组强于吸烟COPD组(P=0.015),前两者又都强于不吸烟非COPD组(P =0.00,P=0.022);③SP-D在肺泡巨噬细胞的表达吸烟非COPD组与吸烟COPD组无明显差异(P=0.313),但前两者都强于不吸烟非COPD组(P=0.00,P=0.005).在吸烟COPD组中,无论是气道上皮细胞、Ⅱ型肺泡上皮细胞还是肺泡巨噬细胞SP-D的表达强度与肺功能均呈正相关.结论 与不吸烟非COPD的人相比,吸烟非COPD和稳定期COPD患者的肺组织中SP-D的表达增强,而吸烟非COPD患者又比吸烟COPD患者SP-D的表达强,SP-D的表达强度与COPD患者的肺功能密切相关,吸烟可能是SP-D表达升高的重要诱因,SP-D表达的下降可能在COPD的发病机制中有重要作用,SP-D可能成为反应COPD严重程度的重要指标.%Objective To investigate the expression of surfactant protein D (SP-D) in smokers and patients of chronic obstructive pulmonary disease (COPD),so as to demonstrate the possible association of SP-D with COPD.Methods The expression of SP-D was detected by immunohistochemical staining.Results ①The expression of SP-D in airway epithelial cells of smoker group was stronger than that in COPD group (P =0.023),which of control group was less than in smoker group and COPD group (P=0.000,P =0.009).②The expression of SP-D in alveolar type Ⅱ epithelial cells of smoker group was stronger than that in COPD group (P =0.015),which of control group was less than in smoker

  6. Scintigraphy for Pulmonary Capillary Protein Leak

    Science.gov (United States)

    1982-09-01

    adrministration (16). The method is noninvasive and has been used clinically to determine the severity and duration of non- cardiogenic pulmonary edema ...If the leak exceeds the 1.iiiphatic capacity, which can increase flow by a factor of 20, pulmcnary interstitial edema occurs. T•hen the interstitial...of shoee is the accepted !::odel for the scudv of pulmonary permehbility - edema (18). It is, therefore, necessary to comnpare our scintigraphic

  7. Interaction of Moringa oleifera seed protein with a mineral surface and the influence of surfactants.

    Science.gov (United States)

    Kwaambwa, Habauka M; Hellsing, Maja S; Rennie, Adrian R; Barker, Robert

    2015-06-15

    The paper describes the adsorption of purified protein from seeds of Moringa oleifera to a sapphire interface and the effects of addition of the anionic surfactant sodium dodecylsulfate (SDS) and the cationic surfactant hexadecyltrimethylammonium bromide (CTAB). Neutron reflection was used to determine the structure and composition of interfacial layers adsorbed at the solid/solution interface. The maximum surface excess of protein was found to be about 5.3 mg m(-2). The protein does not desorb from the solid/liquid interface when rinsed with water. Addition of SDS increases the reflectivity indicating co-adsorption. It was observed that CTAB is able to remove the protein from the interface. The distinct differences to the behavior observed previously for the protein at the silica/water interface are identified. The adsorption of the protein to alumina in addition to other surfaces has shown why it is an effective flocculating agent for the range of impurities found in water supplies. The ability to tailor different surface layers in combination with various surfactants also offers the potential for adsorbed protein to be used in separation technologies.

  8. Protein-nanoparticle interactions evaluation by immunomethods: Surfactants can disturb quantitative determinations.

    Science.gov (United States)

    Fornaguera, Cristina; Calderó, Gabriela; Solans, Conxita; Vauthier, Christine

    2015-08-01

    The adsorption of proteins on nanoparticle surface is one of the first events that occur when nanoparticles enter in the blood stream, which influences nanoparticles lifetime and further biodistribution. Albumin, which is the most abundant protein in serum and which has been deeply characterized, is an interesting model protein to investigate nanoparticle-protein interactions. Therefore, the interaction of nanoparticles with serum albumin has been widely studied. Immunomethods were suggested for the investigation of adsorption isotherms because of their ease to quantify the non-adsorbed bovine serum albumin without the need of applying separation methods that could modify the balance between the adsorbed and non-adsorbed proteins. The present work revealed that this method should be applied with caution. Artifacts in the determination of free protein can be generated by the presence of surfactants such as polysorbate 80, widely used in the pharmaceutical and biomedical field, that are needed to preserve the stability of nanoparticle dispersions. It was shown that the presence of traces of polysorbate 80 in the dispersion leads to an overestimation of the amount of bovine serum albumin remaining free in the dispersion medium when determined by both radial immunodiffusion and rocket immunoelectrophoresis. However, traces of poloxamer 188 did not result in clear perturbed migrations. These methods are not appropriate to perform adsorption isotherms of proteins on nanoparticle dispersions containing traces of remaining free surfactant. They should only be applied on dispersions that are free of surfactant that is not associated with nanoparticles.

  9. Secondary structure and lipid interactions of the N-terminal segment of pulmonary surfactant SP-C in Langmuir films: IR reflection-absorption spectroscopy and surface pressure studies

    DEFF Research Database (Denmark)

    Bi, Xiaohong; Flach, Carol R; Pérez-Gil, Jesus

    2002-01-01

    syndrome, a pathological condition resulting from deficiency in surfactant. To facilitate rational design of therapeutic agents, a molecular level understanding of lipid interaction with surfactant proteins or their analogues in aqueous monolayer films is necessary. The current work uses infrared...

  10. Bio-inspired pulmonary surfactant-modified nanogels : A promising siRNA delivery system

    NARCIS (Netherlands)

    De Backer, Lynn; Braeckmans, Kevin; Stuart, Marc C. A.; Demeester, Jo; De Smedt, Stefaan C.; Raemdonck, Koen

    2015-01-01

    Inhalation therapy with small interfering RNA (siRNA) is a promising approach in the treatment of pulmonary disorders. However, clinical translation is severely limited by the lack of suitable delivery platforms. In this study, we aim to address this limitation by designing a novel bioinspired hybri

  11. Fluorescent Ensemble Based on Bispyrene Fluorophore and Surfactant Assemblies: Sensing and Discriminating Proteins in Aqueous Solution.

    Science.gov (United States)

    Fan, Junmei; Ding, Liping; Bo, Yu; Fang, Yu

    2015-10-14

    A particular bispyrene fluorophore (1) with two pyrene moieties covalently linked via a hydrophilic spacer was synthesized. Fluorescence measurements reveal that the fluorescence emission of 1 could be well modulated by a cationic surfactant, dodecyltrimethylammonium bromide (DTAB). Protein sensing studies illustrate that the selected ensemble based on 1/DTAB assemblies exhibits ratiometric responses to nonmetalloproteins and turn-off responses to metalloproteins, which can be used to differentiate the two types of proteins. Moreover, negatively charged nonmetalloproteins can be discriminated from the positively charged ones according to the difference in ratiometric responses. Fluorescence sensing studies with control bispyrenes indicate that the polarity of the spacer connecting two pyrene moieties plays an important role in locating bispyrene fluorophore in DTAB assemblies, which further influences its sensing behaviors to noncovalent interacting proteins. This study sheds light on the influence of the probe structure on the sensing performance of a fluorescent ensemble based on probe and surfactant assemblies.

  12. PLUNC is a novel airway surfactant protein with anti-biofilm activity.

    Directory of Open Access Journals (Sweden)

    Lokesh Gakhar

    Full Text Available BACKGROUND: The PLUNC ("Palate, lung, nasal epithelium clone" protein is an abundant secretory product of epithelia present throughout the conducting airways of humans and other mammals, which is evolutionarily related to the lipid transfer/lipopolysaccharide binding protein (LT/LBP family. Two members of this family--the bactericidal/permeability increasing protein (BPI and the lipopolysaccharide binding protein (LBP--are innate immune molecules with recognized roles in sensing and responding to Gram negative bacteria, leading many to propose that PLUNC may play a host defense role in the human airways. METHODOLOGY/PRINCIPAL FINDINGS: Based on its marked hydrophobicity, we hypothesized that PLUNC may be an airway surfactant. We found that purified recombinant human PLUNC greatly enhanced the ability of aqueous solutions to spread on a hydrophobic surface. Furthermore, we discovered that PLUNC significantly reduced surface tension at the air-liquid interface in aqueous solutions, indicating novel and biologically relevant surfactant properties. Of note, surface tensions achieved by adding PLUNC to solutions are very similar to measurements of the surface tension in tracheobronchial secretions from humans and animal models. Because surfactants of microbial origin can disperse matrix-encased bacterial clusters known as biofilms [1], we hypothesized that PLUNC may also have anti-biofilm activity. We found that, at a physiologically relevant concentration, PLUNC inhibited biofilm formation by the airway pathogen Pseudomonas aeruginosa in an in vitro model. CONCLUSIONS/SIGNIFICANCE: Our data suggest that the PLUNC protein contributes to the surfactant properties of airway secretions, and that this activity may interfere with biofilm formation by an airway pathogen.

  13. Structure and dynamics of a protein-surfactant assembly studied by ion-mobility mass spectrometry and molecular dynamics simulations.

    Science.gov (United States)

    Borysik, Antoni J

    2015-09-01

    The structure and dynamics of a protein-surfactant assembly studied by ion-mobility mass spectrometry (IMS) and vacuum molecular dynamics (MD) simulations is reported. Direct evidence is provided for the ability of the surfactant dodecyl-β-D-maltoside (DDM) to prevent charge-induced unfolding of the membrane protein (PagP) in the gas-phase. Restraints obtained by IMS are used to map the surfactant positions onto the protein surface. Surfactants occupying more exposed positions at the apexes of the β-barrel structure are most in-line with the experimental observations. MD simulations provide additional evidence for this assembly organization through surfactant inversion and migration on the protein structure in the absence of solvent. Surfactant migration entails a net shift from apolar membrane spanning regions to more polar regions of the protein structure with the DDM molecule remaining attached to the protein via headgroup interactions. These data provide evidence for the role of protein-DDM headgroup interactions in stabilizing membrane protein structure from gas-phase unfolding.

  14. Immunocytochemical localization of the surfactant apoprotein and Clara cell antigen in chemically induced and naturally occurring pulmonary neoplasms of mice.

    Science.gov (United States)

    Ward, J. M.; Singh, G.; Katyal, S. L.; Anderson, L. M.; Kovatch, R. M.

    1985-01-01

    The localization of surfactant apoprotein (SAP) and the Clara cell antigen(s) (CCA) was studied in naturally occurring and experimentally induced pulmonary hyperplasias and neoplasms by avidin-biotin peroxidase complex (ABC) immunocytochemistry. Lungs of B6C3F1 and A strain mice with naturally occurring lesions, B6C3F1 mice given injections of N-nitrosodiethylamine (DEN), BALB/c nu/nu or nu/+ mice exposed transplacentally on Day 16 of gestation to ethylnitrosourea (ENU), or BALB/c nu/+ mice exposed to ENU at 8-12 weeks of age were preserved in formalin or Bouin's fixative. After ABC immunocytochemistry, SAP was found in the cytoplasm of normal alveolar Type II cells; in the majority of cells in focal alveolar and solid hyperplasias originating in peribronchiolar or peripheral locations; and in solid, tubular, papillary, and mixed adenomas and carcinomas. The larger mixed-pattern neoplasms and small or large tubular neoplasms usually had the least number of cells with SAP. The majority of large papillary adenomas and carcinomas in BALB/c mice exposed to ENU and in untreated A strain mice contained SAP in the nuclei of many neoplastic cells but only in the cytoplasm of a few neoplastic cells. CCA was found in normal Clara cells of bronchi and bronchioles but not in any hyperplastic or neoplastic lesion of any mouse studied. This study provided immunocytochemical evidence that the vast majority of naturally occurring and experimentally induced pulmonary neoplasms of mice are alveolar Type II cell adenomas and carcinomas. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:3883798

  15. An investigation of the carbon nanotube--Lipid interface and its impact upon pulmonary surfactant lipid function.

    Science.gov (United States)

    Melbourne, Jodie; Clancy, Adam; Seiffert, Joanna; Skepper, Jeremy; Tetley, Teresa D; Shaffer, Milo S P; Porter, Alexandra

    2015-07-01

    Multiwalled carbon nanotubes (MWCNTs) are now synthesized on a large scale, increasing the risk of occupational inhalation. However, little is known of the MWCNT-pulmonary surfactant (PS) interface and its effect on PS functionality. The Langmuir-Blodgett trough was used to evaluate the impact of MWCNTs on fundamental properties of PS lipids which influence PS function, i.e. compression resistance and maximum obtainable pressure. Changes were found to be MWCNT length-dependent. 'Short' MWCNTs (1.1 μm, SD = 0.61) penetrated the lipid film, reducing the maximum interfacial film pressure by 10 mN/m (14%) in dipalmitoylphosphatidylcholine (DPPC) and PS, at an interfacial MWCNT-PS lipid mass ratio range of 50:1 to 1:1. 'Long' commercial MWCNTs (2.1 μm, SD = 1.2) caused compression resistance at the same mass loadings. 'Very long' MWCNTs (35 μm, SD = 19) sequestered DPPC and were squeezed out of the DPPC film. High resolution transmission electron microscopy revealed that all MWCNT morphologies formed DPPC coronas with ordered arrangements. These results provide insight into how nanoparticle aspect ratio affects the interaction mechanisms with PS, in its near-native state at the air-water interface.

  16. Latherin: a surfactant protein of horse sweat and saliva.

    Directory of Open Access Journals (Sweden)

    Rhona E McDonald

    Full Text Available Horses are unusual in producing protein-rich sweat for thermoregulation, a major component of which is latherin, a highly surface-active, non-glycosylated protein. The amino acid sequence of latherin, determined from cDNA analysis, is highly conserved across four geographically dispersed equid species (horse, zebra, onager, ass, and is similar to a family of proteins only found previously in the oral cavity and associated tissues of mammals. Latherin produces a significant reduction in water surface tension at low concentrations (< or = 1 mg ml(-1, and therefore probably acts as a wetting agent to facilitate evaporative cooling through a waterproofed pelt. Neutron reflection experiments indicate that this detergent-like activity is associated with the formation of a dense protein layer, about 10 A thick, at the air-water interface. However, biophysical characterization (circular dichroism, differential scanning calorimetry in solution shows that latherin behaves like a typical globular protein, although with unusual intrinsic fluorescence characteristics, suggesting that significant conformational change or unfolding of the protein is required for assembly of the air-water interfacial layer. RT-PCR screening revealed latherin transcripts in horse skin and salivary gland but in no other tissues. Recombinant latherin produced in bacteria was also found to be the target of IgE antibody from horse-allergic subjects. Equids therefore may have adapted an oral/salivary mucosal protein for two purposes peculiar to their lifestyle, namely their need for rapid and efficient heat dissipation and their specialisation for masticating and processing large quantities of dry food material.

  17. Application of polyhydroxyalkanoate binding protein PhaP as a bio-surfactant.

    Science.gov (United States)

    Wei, Dai-Xu; Chen, Chong-Bo; Fang, Guo; Li, Shi-Yan; Chen, Guo-Qiang

    2011-08-01

    PhaP or phasin is an amphiphilic protein located on surfaces of microbial storage polyhydroxyalkanoates granules. This study aimed to explore amphiphilic properties of PhaP for possible application as a protein surfactant. Following agents were used to conduct this study as controls including bovine serum albumin, sodium dodecyl sulfate (SDS), Tween 20, sodium oleate, a commercial liquefied detergent together with the same amount of PhaP. Among all these tested control surfactants, PhaP showed the strongest effect to form emulsions with lubricating oil, diesel, and soybean oil, respectively. PhaP emulsion stability study compared with SDS revealed that PhaP had a stronger capability to maintain a very stable emulsion layer after 30 days while SDS lost half and two-thirds of its capacity after 2 and 30 days, respectively. When PhaP was more than 200 μg/ml in the water, all liquids started to exhibit stable emulsion layers. Similar to SDS, PhaP significantly reduced the water contact angles of water on a hydrophobic film of biaxially oriented polypropylene. PhaP was thermally very stable, it showed ability to form emulsion and to bind to the surface of polyhydroxybutyrate nanoparticles after a 60- min heating process at 95 °C. It is therefore concluded that PhaP is a protein with thermally stable property for application as natural and environmentally friendly surfactant for food, cosmetic, and pharmaceutical usages.

  18. Surfactant protein (SP)-A and SP-D as antimicrobial and immunotherapeutic agents.

    Science.gov (United States)

    Awasthi, Shanjana

    2010-06-01

    Surfactant protein (SP)-A and SP-D belong to the "Soluble C-type Lectin" family of proteins and are collectively known as "Collectins". Based on their ability to recognize pathogens and to regulate the host defense, SP-A and SP-D have been recently categorized as "Secretory Pathogen Recognition Receptors". SP-A and SP-D were first identified in the lung; the expression of SP-A and SP-D has also been observed at other mucosal surfaces, such as lacrimal glands, gastrointestinal mucosa, genitourinary epithelium and periodontal surfaces. Since the role of these proteins is not fully elucidated at other mucosal surfaces, the focus of this article is on lung-SP-A and SP-D. It has become clear from research studies performed over a number of years that SP-A and SP-D are critical for the maintenance of lung homeostasis and the regulation of host defense and inflammation. However, none of the surfactant preparations available for clinical use have SP-A or SP-D. A review is presented here on SP-A- and SP-D-deficiencies in lung diseases, the importance of the administration of SP-A and SP-D, and recent patents and research directions that may lead to the design of novel SP-A- or SP-D-based therapeutics and surfactants.

  19. Purification, characterization and immunolocalization of porcine surfactant protein D

    DEFF Research Database (Denmark)

    Sørensen, C.M.; Nielsen, Ove Lilholm; Willis, A.

    2005-01-01

    chromatography. The purified protein appeared on sodium dodecyl sulphate-polyacrylamide gel electrophoresis as a band of similar to53 000 MW in the reduced state and similar to138 000 MW in the unreduced state. Porcine SP-D was sensitive to collagenase digestion and N-deglycosylation, which reduced the molecular...

  20. Genetic and environmental influences of surfactant protein D serum levels

    DEFF Research Database (Denmark)

    Sørensen, Grith Lykke; Hjelmborg, Jacob v. B.; Kyvik, Kirsten Ohm

    2006-01-01

    in the NH(2)-terminal region (Met11Thr) of the mature protein is significantly associated with the serum SP-D levels. A classic twin study was performed on a twin population including 1,476 self-reported healthy adults. The serum SP-D levels increased with male sex, age, and smoking status. The intraclass...

  1. Biophysical mimicry of lung surfactant protein B by random nylon-3 copolymers.

    Science.gov (United States)

    Dohm, Michelle T; Mowery, Brendan P; Czyzewski, Ann M; Stahl, Shannon S; Gellman, Samuel H; Barron, Annelise E

    2010-06-16

    Non-natural oligomers have recently shown promise as functional analogues of lung surfactant proteins B and C (SP-B and SP-C), two helical and amphiphilic proteins that are critical for normal respiration. The generation of non-natural mimics of SP-B and SP-C has previously been restricted to step-by-step, sequence-specific synthesis, which results in discrete oligomers that are intended to manifest specific structural attributes. Here we present an alternative approach to SP-B mimicry that is based on sequence-random copolymers containing cationic and lipophilic subunits. These materials, members of the nylon-3 family, are prepared by ring-opening polymerization of beta-lactams. The best of the nylon-3 polymers display promising in vitro surfactant activities in a mixed lipid film. Pulsating bubble surfactometry data indicate that films containing the most surface-active polymers attain adsorptive and dynamic-cycling properties that surpass those of discrete peptides intended to mimic SP-B. Attachment of an N-terminal octadecanoyl unit to the nylon-3 copolymers, inspired by the post-translational modifications found in SP-C, affords further improvements by reducing the percent surface area compression to reach low minimum surface tension. Cytotoxic effects of the copolymers are diminished relative to that of an SP-B-derived peptide and a peptoid-based mimic. The current study provides evidence that sequence-random copolymers can mimic the in vitro surface-active behavior of lung surfactant proteins in a mixed lipid film. These findings raise the possibility that random copolymers might be useful for developing a lung surfactant replacement, which is an attractive prospect given that such polymers are easier to prepare than are sequence-specific oligomers.

  2. Factors affecting protein transfer into surfactant-isooctane solution: a case study of extraction behavior of chemically modified cytochrome c.

    Science.gov (United States)

    Ono, T; Goto, M

    1998-01-01

    The extraction mechanism of proteins by surfactant molecules in an organic solvent has been investigated using a chemically modified protein. We conducted guanidylation on lysine residues of cytochrome c by replacing their amino groups with homoarginine to enhance the protein-surfactant interaction. Results have shown that guanidylated cytochrome c readily forms a hydrophobic complex with dioleyl phosphoric acid (DOLPA) through hydrogen bonding between the phosphate moiety and the guanidinium groups. Although improved protein-surfactant interaction activated the formation of a hydrophobic complex at the interface, it could not improve the protein transfer in isooctane. It has been established that the protein extraction mechanism using surfactant molecules is mainly governed by two processes: formation of an interfacial complex at the oil-water interface and the subsequent solubilization of the complex into the organic phase. In addition, a kinetic study demonstrated that guanidylation of lysine accelerated the initial extraction rate of cytochrome c. This fact implies that the protein transferability from aqueous phase into organic phase depends on the protein-surfactant interaction which can be modified by protein surface engineering.

  3. Protective effects of surfactant protein D treatment in 1,3-β-glucan-modulated allergic inflammation.

    Science.gov (United States)

    Fakih, Dalia; Pilecki, Bartosz; Schlosser, Anders; Jepsen, Christine S; Thomsen, Laura K; Ormhøj, Maria; Watson, Alastair; Madsen, Jens; Clark, Howard W; Barfod, Kenneth K; Hansen, Soren; Marcussen, Niels; Jounblat, Rania; Chamat, Soulaima; Holmskov, Uffe; Sorensen, Grith L

    2015-12-01

    Surfactant protein D (SP-D) is a pulmonary collectin important in lung immunity. SP-D-deficient mice (Sftpd(-/-)) are reported to be susceptible to ovalbumin (OVA)- and fungal allergen-induced pulmonary inflammation, while treatment with exogenous SP-D has therapeutic effects in such disease models. β-Glucans are a diverse group of polysaccharides previously suggested to serve as fungal ligands for SP-D. We set out to investigate if SP-D could interact with 1,3-β-glucan and attenuate allergic pulmonary inflammation in the presence of 1,3-β-glucan. Allergic airway disease was induced in Sftpd(-/-) and Sftpd(+/+) mice by OVA sensitization and subsequent challenge with OVA, 1,3-β-glucan, or OVA/1,3-β-glucan together. Mice in the combined treatment group were further treated with a high dose of recombinant fragment of human SP-D (rfhSP-D). We demonstrated direct interaction between SP-D and 1,3-β-glucan. OVA-induced mucous cell metaplasia was increased in Sftpd(-/-) mice, supporting previously reported protective effects of endogenous SP-D in allergy. OVA-induced parenchymal CCL11 levels and eosinophilic infiltration in bronchoalveolar lavage were unaffected by 1,3-β-glucan, but were reversed with rfhSP-D treatment. 1,3-β-Glucan treatment did, however, induce pulmonary neutrophilic infiltration and increased TNF-α levels in bronchoalveolar lavage, independently of OVA-induced allergy. This infiltration was also reversed by treatment with rfhSP-D. 1,3-β-Glucan reduced OVA-induced mucous cell metaplasia, T helper 2 cytokines, and IFN-γ production. rfhSP-D treatment further reduced mucous metaplasia and T helper 2 cytokine secretion to background levels. In summary, rfhSP-D treatment resulted in attenuation of both allergic inflammation and 1,3-β-glucan-mediated neutrophilic inflammation. Our data suggest that treatment with high-dose SP-D protects from mold-induced exacerbations of allergic asthma.

  4. Microfibril-associated Protein 4 Binds to Surfactant Protein A (SP-A) and Colocalizes with SP-A in the Extracellular Matrix of the Lung

    DEFF Research Database (Denmark)

    Schlosser, Anders; Thomsen, Theresa H.; Shipley, J. Michael

    2006-01-01

    Pulmonary surfactant protein A (SP-A) is an oligomeric collectin that recognizes lipid and carbohydrate moieties present on broad range of micro-organisms, and mediates microbial lysis and clearance. SP-A also modulates multiple immune-related functions including cytokine production and chemotaxis...... for phagocytes. Here we describe the molecular interaction between the extracellular matrix protein microfibril-associated protein 4 (MFAP4) and SP-A. MFAP4 is a collagen-binding molecule containing a C-terminal fibrinogen-like domain and a N-terminal located integrin-binding motif. We produced recombinant MFAP4...... with a molecular mass of 36 and 66 kDa in the reduced and unreduced states respectively. Gel filtration chromatography and chemical crosslinking showed that MFAP4 forms oligomers of four dimers. We demonstrated calcium-dependent binding between MFAP4 and human SP-A1 and SP-A2. No binding was seen to recombinant SP-A...

  5. Role of the N-terminal seven residues of surfactant protein B (SP-B.

    Directory of Open Access Journals (Sweden)

    Mahzad Sharifahmadian

    Full Text Available Breathing is enabled by lung surfactant, a mixture of proteins and lipids that forms a surface-active layer and reduces surface tension at the air-water interface in lungs. Surfactant protein B (SP-B is an essential component of lung surfactant. In this study we probe the mechanism underlying the important functional contributions made by the N-terminal 7 residues of SP-B, a region sometimes called the "insertion sequence". These studies employed a construct of SP-B, SP-B (1-25,63-78, also called Super Mini-B, which is a 41-residue peptide with internal disulfide bonds comprising the N-terminal 7-residue insertion sequence and the N- and C-terminal helices of SP-B. Circular dichroism, solution NMR, and solid state (2H NMR were used to study the structure of SP-B (1-25,63-78 and its interactions with phospholipid bilayers. Comparison of results for SP-B (8-25,63-78 and SP-B (1-25,63-78 demonstrates that the presence of the 7-residue insertion sequence induces substantial disorder near the centre of the lipid bilayer, but without a major disruption of the overall mechanical orientation of the bilayers. This observation suggests the insertion sequence is unlikely to penetrate deeply into the bilayer. The 7-residue insertion sequence substantially increases the solution NMR linewidths, most likely due to an increase in global dynamics.

  6. Human salivary agglutinin binds to lung surfactant protein-D and is identical with scavenger receptor protein gp-340

    DEFF Research Database (Denmark)

    Ligtenberg, T J; Bikker, F J; Groenink, J

    2001-01-01

    bound in a similar way to Streptococcus mutans and surfactant protein-D. Histochemically, the distribution of gp-340 in the submandibular salivary glands was identical with the agglutinin distribution, as shown in a previous paper [Takano, Bogert, Malamud, Lally and Hand (1991) Anat. Rec. 230, 307......Salivary agglutinin is a 300-400 kDa salivary glycoprotein that binds to antigen B polypeptides of oral streptococci, thereby playing a role in their colonization and the development of caries. A mass spectrum was recorded of a trypsin digest of agglutinin. A dominant peak of 1460 Da was sequenced...... of gp-340. gp-340 is a 340 kDa glycoprotein isolated from bronchoalveolar lavage fluid that binds specifically to lung surfactant protein-D. DMBT1 is a candidate tumour suppressor gene. A search in the human genome revealed only one copy of this gene. The molecular mass, as judged from SDS...

  7. Effect of silk protein surfactant on silk degumming and its properties.

    Science.gov (United States)

    Wang, Fei; Cao, Ting-Ting; Zhang, Yu-Qing

    2015-10-01

    The silk protein surfactant (SPS) first used as a silk degumming agent in this study is an amino acid-type anionic surfactant that was synthesized using silk fibroin amino acids and lauroyl chloride. We studied it systematically in comparison with the traditional degumming methods such as sodium carbonate (Na2CO3) and neutral soap (NS). The experimental results showed that the sericin can be completely removed from the silk fibroin fiber after boiling the fibers three times for 30 min and using a bath ratio of 1:80 (g/mL) and a concentration of 0.2% SPS in an aqueous solution. The results of the tensile properties, thermal analysis, and SEM all show that SPS is similar to the NS, far superior to Na2CO3. In short, SPS may be used as an environmentally friendly silk degumming/refining agent in the silk textile industry and in the manufacture of silk floss quilts.

  8. Reduced influenza viral neutralizing activity of natural human trimers of surfactant protein D

    DEFF Research Database (Denmark)

    Hartshorn, Kevan L; White, Mitchell R; Tecle, Tesfaldet

    2007-01-01

    BACKGROUND: Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection. Common human polymorphisms of SP-D have been found in many human populations and associated with increased risk of certain infections. We recently reported that the Thr...... human SP-D multimers as well as reduced hemagglutination inhibiting activity against several strains of IAV. Natural SP-D trimers also had different interactions with human neutrophil peptide defensins (HNPs) in viral neutralization assays as compared to multimeric SP-D. CONCLUSION: These studies......-D can be useful for dissecting out different functional properties of the protein....

  9. Genetic and environmental influences of surfactant protein D serum levels

    DEFF Research Database (Denmark)

    Sorensen, G.L.; Hjelmborg, J.V.; Kyvik, K.O.

    2006-01-01

    defining the constitutional serum level of SP-D and determine the magnitude of the genetic contribution to serum SP-D in the adult population. Recent studies have demonstrated that serum SP-D concentrations in children are genetically determined and that a single nucleotide polymorphism (SNP) located...... in the NH(2)-terminal region (Met11Thr) of the mature protein is significantly associated with the serum SP-D levels. A classic twin study was performed on a twin population including 1,476 self-reported healthy adults. The serum SP-D levels increased with male sex, age, and smoking status. The intraclass...... correlation was significantly higher for monozygotic (MZ) twin pairs than for dizygotic (DZ) twin pairs. Serum SP-D variance was influenced by nonshared environmental effects and additive genetic effects. Multivariate analysis of MZ and DZ covariance matrixes showed significant genetic correlation among serum...

  10. Biosurfactants and surfactants interacting with membranes and proteins: Same but different?

    Science.gov (United States)

    Otzen, Daniel E

    2017-04-01

    Biosurfactants (BS) are surface-active molecules produced by microorganisms. For several decades they have attracted interest as promising alternatives to current petroleum-based surfactants. Aside from their green profile, they have remarkably low critical micelle concentrations, reduce the air/water surface tension to very low levels and are excellent emulsifiers, all of which make them comparable or superior to their synthetic counterparts. These remarkable physical properties derive from their more complex chemical structures in which hydrophilic and hydrophobic regions are not as clearly separated as chemical surfactants but have a more mosaic distribution of polarity as well as branched or circular structures. This allows the lipopeptide surfactin to adopt spherical structures to facilitate dense packing at interfaces. They are also more complex. Glycolipid BS, e.g. rhamnolipids (RL) and sophorolipids, are produced biologically as mixtures which vary in the size and saturation of the hydrophobic region as well as modifications in the hydrophilic headgroup, such as the number of sugar groups and different levels of acetylation, leading to variable surface-active properties. Their amphiphilicity allows RL to insert easily into membranes at sub-cmc concentrations to modulate membrane structure and extract lipopolysaccharides, leading to extensive biofilm remodeling in vivo, sometimes in collaboration with hydrophobic RL precursors. Thanks to their mosaicity, even anionic BS like RL only bind weakly to proteins and show much lower denaturing potency, even supporting membrane protein refolding. Nevertheless, they can promote protein degradation by proteases e.g. by neutralizing positive charges, which together with their biofilm-combating properties makes them very promising detergent surfactants. This article is part of a Special Issue entitled: Lipid order/lipid defects and lipid-control of protein activity edited by Dirk Schneider.

  11. Altered surfactant protein A gene expression and protein homeostasis in rats with emphysematous changes

    Institute of Scientific and Technical Information of China (English)

    HU Qiong-jie; XIONG Sheng-dao; ZHANG Hui-lan; SHI Xue-mei; XU Yong-jian; ZHANG Zhen-xiang; ZHEN Guo-hua; ZHAO Jian-ping

    2008-01-01

    Background The decrease of suffactant protein(SP)secreted by the alveolar type Ⅱ cell is one of the important causes of limiting air of pulmonary emphysema.However,the SP-A gene and protein changes in this disease are rarely studied.This study was undertaken to investigate alterations in SP-A gene activity and protein,and to explore their roles in the pathogenesis of emphysematous changes.Methods Twenty Wistar rats were divided randomly into a normal control group(n=10)and a cigarette smoking(CS)+lipopolysaccharide(LPS)group(n=10).Ultra-structural changes were obsewed under an electron microscope.The number of cells positive for SP-A was measured by immunohistochemistry.The mRNA expression and protein Ievel of SP-A in the lung tissues were determined by quantitative polymerase chain reaction(qPCR)and Western blot separately.The protein level of SP-A in lavage fluid was determined by Western blot.Results The number of cells positive for SP-A of the CS+LPS group(0.35±0.03)was lower than that of the blank control group(0.72±0.06,P<0.05).The level of SP-A in the lung tissues of rats in the CS+LPS group(0.2765±0.0890)was lower than that in the blank controI group(0.6875±0.1578,P<0.05).The level of SP-A in the lavage fluid of rats in the CS+LPS group(0.8567±0.1458)was lower than that in the blank controI group(1.3541±0.2475,P<0.05).The lung tissues of rats in the CS+LPS group showed an approximate increase(0.4-fold)in SP-A mRNA levels relative to β-actin mRNA (P<0.05).Conclusions The changes of SP-A may be related to emphysematous changes in the lung.And cigarette smoke and LPS alter lung SP-A gene activity and protein homeostasis.

  12. Protein-surfactant interactions at hydrophobic interfaces studied with total internal reflection fluorescence correlation spectroscopy (TIR-FCS).

    Science.gov (United States)

    Sonesson, Andreas W; Blom, Hans; Hassler, Kai; Elofsson, Ulla M; Callisen, Thomas H; Widengren, Jerker; Brismar, Hjalmar

    2008-01-15

    The aim of this work was to study the dynamics of proteins near solid surfaces in the presence or absence of competing surfactants by means of total internal reflection fluorescence correlation spectroscopy (TIR-FCS). Two different proteins were studied, bovine serum albumin (BSA) and Thermomyces lanuginosus lipase (TLL). A nonionic/anionic (C12E6/LAS) surfactant composition was used to mimic a detergent formulation and the surfaces used were C18 terminated glass. It was found that with increasing surfactant concentrations the term in the autocorrelation function (ACF) representing surface binding decreased. This suggested that the proteins were competed off the hydrophobic surface by the surfactant. When fitting the measured ACF to a model for surface kinetics, it was seen that with raised C12E6/LAS concentration, the surface interaction rate increased for both proteins. Under these experimental conditions this meant that the time the protein was bound to the surface decreased. At 10 microM C12E6/LAS the surface interaction was not visible for BSA, whereas it was still distinguishable in the ACF for TLL. This indicated that TLL had a higher affinity than BSA for the C18 surface. The study showed that TIR-FCS provides a useful tool to quantify the surfactant effect on proteins adsorption.

  13. Circulating surfactant protein D as a potential lung-specific biomarker of health outcomes in COPD: a pilot study

    Directory of Open Access Journals (Sweden)

    Man SF Paul

    2007-10-01

    Full Text Available Abstract Background There is a paucity of surrogate lung-specific biological markers that can be used to track disease progression and predict clinical outcomes in chronic obstructive pulmonary disease (COPD. The principal aim of this pilot study was to determine whether circulating surfactant protein D (SPD or Clara Cell protein-16 (CC16 levels are associated with lung function or health status in patients with severe COPD. Methods We studied 23 patients with advanced COPD. Lung function measurements, Chronic Respiratory Disease Questionnaire (CRQ scores, and serum levels of SPD, CC16, and C-reactive protein (CRP were determined at baseline and at 3 months. Results At baseline, FEV1 was inversely associated with serum SPD levels (P = 0.045 but not with CC16 (P = 0.675 or CRP levels (P = 0.549. Over a 3 month period, changes in SPD levels correlated significantly with changes in CRQ scores (adjusted P = 0.008 such that patients who had the largest declines in serum SPD levels experienced the largest gains in health status. The association was particularly notable between circulating SPD level and the dyspnea domain of the CRQ score (P = 0.018. Changes in CC16 or CRP levels did not correlate with changes in CRQ scores. Conclusion Changes in serum SPD levels tracked well with changes in health status over a 3 month period in patients with severe COPD. These data suggest that circulating SPD levels may be useful biomarkers to track health outcomes of COPD patients.

  14. Correlation of mineral dust-induced changes in the composition of a fraction enriched in lung surfactant with pulmonary histologic lesions in rats

    Energy Technology Data Exchange (ETDEWEB)

    Schengrund, C.-L.; Griffith, J.W.; Wilson, R.P.; Xiaoli Chi [Pennsylvania State University, Hershey, PA (United States). Dept. of Biochemistry and Molecular Biology

    1996-07-01

    In previous work the composition of surfactant isolated from cell-free bronchoalveolar lavage (CF-BAL) from the right lungs of monkeys instilled with 500 mg of either generic bituminous, anthracite, quartz, or titanium dioxide dust was compared with that of surfactant isolated from CF-BAL from control left lungs. Exposure to quartz, anthracite, or titanium dioxide induced a significant increase in the amount of protein recovered, which was evident throughout most of the time period (1 year) studied. Exposure to quartz also induced a significant decrease in the total amount of lipid-associated phosphorus. To determine whether dust-induced changes in surfactant composition paralleled changes in lung morphology, consecutive studies were carried out in rats. Rats were instilled with 50 mg of either quartz or anthracite dust/kilogram body weight. One milligram of bituminous dust was intilled with every 5 mg of quartz dust as a marker to indicate dust location. Histologic evaluation of quartz dust-exposed lungs showed alveolitis, including microgranulomas, which were associated with clusters of dust-containing macrophages and polymorphonuclear cells which were localized within alveoli and interstitium surrounding small bronchioles. The anthracite dust-exposed lungs contained similar cell types localized around small bronchioles, which did not form microgranulomas. Surfactant protein A was found within alveolar type II cells and macrophages of both rat and primate lungs, but not within macrophages markedly distended with dust particles. The number of alveolar type II cells appeared to increase in response to the length of time of exposure to dust, as did the total amount of protein recovered in the surfactant-enriched fractions prepared from CF-BAL from dust-instilled lungs relative to that in surfactant-enriched fractions isolated from CF-BAL from control lungs. 26 refs., 2 figs., 2 tabs.

  15. Nonlinear Surface Dilatational Rheology and Foaming Behavior of Protein and Protein Fibrillar Aggregates in the Presence of Natural Surfactant.

    Science.gov (United States)

    Wan, Zhili; Yang, Xiaoquan; Sagis, Leonard M C

    2016-04-19

    The surface and foaming properties of native soy glycinin (11S) and its heat-induced fibrillar aggregates, in the presence of natural surfactant steviol glycoside (STE), were investigated and compared at pH 7.0 to determine the impact of protein structure modification on protein-surfactant interfacial interactions. The adsorption at, and nonlinear dilatational rheological behavior of, the air-water interface were studied by combining drop shape analysis tensiometry, ellipsometry, and large-amplitude oscillatory dilatational rheology. Lissajous plots of surface pressure versus deformation were used to analyze the surface rheological response in terms of interfacial microstructure. The heat treatment generates a mixture of long fibrils and unconverted peptides. The presence of small peptides in 11S fibril samples resulted in a faster adsorption kinetics than that of native 11S. The addition of STE affected the adsorption of 11S significantly, whereas no apparent effect on the adsorption of the 11S fibril-peptide system was observed. The rheological response of interfaces stabilized by 11S-STE mixtures also differed significantly from the response for 11S fibril-peptide-STE mixtures. For 11S, the STE reduces the degree of strain hardening in extension and increases strain hardening in compression, suggesting the interfacial structure may change from a surface gel to a mixed phase of protein patches and STE domains. The foams generated from the mixtures displayed comparable foam stability to that of pure 11S. For 11S fibril-peptide mixtures STE only significantly affects the response in extension, where the degree of strain softening is decreased compared to the pure fibril-peptide system. The foam stability of the fibril-peptide system was significantly reduced by STE. These findings indicate that fibrillization of globular proteins could be a potential strategy to modify the complex surface and foaming behaviors of protein-surfactant mixtures.

  16. Surfactants and the Mechanics of Respiration

    Science.gov (United States)

    Jbaily, Abdulrahman; Szeri, Andrew J.

    2016-11-01

    Alveoli are small sacs found at the end of terminal bronchioles in human lungs with a mean diameter of 200 μm. A thin layer of fluid (hypophase) coats the inner face of an alveolus and is in contact with the air in the lungs. The thickness of this layer varies among alveoli, but is in the range of 0.1 to 0.5 μm for many portions of the alveolar network. The interfacial tension σ at the air-hypophase interface tends to favor collapse of the alveolus, and resists its expansion during inhalation. Type II alveolar cells synthesize and secrete a mixture of phospholipids and proteins called pulmonary surfactant. These surfactant molecules adsorb to the interface causing σ of water at body temperature is 70 mN/m and falls to an equilibrium value of 25 mN/m when surfactants are present. Also, in a dynamic sense, it is known that σ is reduced to near 0 during exhalation when the surfactant film compresses. In this work, the authors develop a mechanical and transport model of the alveolus to study the effect of surfactants on various aspects of respiration. The model is composed of three principal parts: (i) air movement into and out of the alveolus; (ii) a balance of linear momentum across the two-layered membrane of the alveolus (hypophase and elastic wall); and (iii) a pulmonary surfactant transport problem in the hypophase. The goal is to evaluate the influence of pulmonary surfactant on respiratory mechanics.

  17. Changes of Tumor Necrosis Factor, Surfactant Protein A, and Phospholipids in Bronchoalveolar Lavage Fluid in the Development and Progression of Coal Workers' Pneumoconiosis

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    To evaluate the alterations of biomarkers in the development and progression of coal workers'pneumoconiosis (CWP). Methods The type and number of cells, and the levels of tumor necrosis factor-alpha (TNF-α),pulmonary surfactant protein, phospholipids and fibronectin in bronchoalveolar lavage fluid were assayed in 14 health active coal miners, 21 coal miners without CWP and 13 miners with CWP of 0/1 to 1/1. Results Compared to active coal miners without CWP (8.23 μg/mL), TNF-α concentration was gradually decreased when dust exposure was stopped (5.90 μg/mL).Elevated surfactant protein A (SP-A) level and phosphatidylglycerol (PG) to phosphatidylinositol (PI) ratio were found in miners actively exposed to coal dust (6528 ng/mL for SP-A and 10. for PG/PI), and both parameters decreased when CWP progressed from CWP (0/1) (3419 μg/mL for SP-A and 5.9 for PG/PI) to CWP (1/1) (1654 μg/mL for SP-A and 5.5 for PG/PI).Conclusion Biomarkers in bronchoalveolar lavage fluid can be used to screen coal miners at high risk of developing coal workers' pneumoconiosis.

  18. THE CONCENTRATION OF SURFACTANT PROTEIN-A IN AMNIOTIC FLUID DECREASES IN SPONTANEOUS HUMAN PARTURITION AT TERM

    Science.gov (United States)

    Chaiworapongsa, Tinnakorn; Hong, Joon-Seok; Hull, William M.; Kim, Chong Jai; Gomez, Ricardo; Mazor, Moshe; Romero, Roberto; Whitsett, Jeffrey A.

    2012-01-01

    OBJECTIVE The fetus is thought to play a central role in the onset of labor. Pulmonary surfactant protein (SP)-A, secreted by the maturing fetal lung, has been implicated in the mechanisms initiating parturition in mice. The present study was conducted to determine whether amniotic fluid concentrations of SP-A and SP-B change during human parturition. STUDY DESIGN Amniotic fluid SP-A and SP-B concentrations were measured with sensitive and specific ELISA in the following groups of pregnant women: 1) mid-trimester of pregnancy between 15th and 18th weeks of gestation (n=29); 2) term pregnancy not in labor (n=28); and 3) term pregnancy in spontaneous labor (n=26). Non-parametric statistics were used for analysis. RESULTS SP-A was detected in all amniotic fluid samples. SP-B was detected in 24.1% (7/29) of mid-trimester samples and in all samples at term. The median amniotic fluid concentration of SP-A and SP-B were significantly higher in women at term than in women in the mid-trimester (SP-A term no labor: median 5.6 μg/ml, range 2.2–15.2 μg/ml vs. mid-trimester: median 1.64 μg/ml, range 0.1–4.7 μg/ml; and SP-B term no labor: median 0.54 μg/ml, range 0.17–1.99 μg/ml vs. mid-trimester: median 0 μg/ml, range 0–0.35 μg/ml; both plabor was significantly lower than that in women at term not in labor (term in labor: median 2.7 μg/ml, range 1.2–10.1 μg/ml vs. term no labor: median 5.6 μg/ml, range 2.2–15.2 μg/ml; plabor and those not in labor (term in labor: median 0.47 μg/ml range 0.04–1.32 μg/ml vs. term no labor: median 0.54 μg/ml range 0.17–1.99 μg/ml; p=0.2). CONCLUSION The amniotic fluid concentration of surfactant protein-A decreases in spontaneous human parturition at term. PMID:18828058

  19. Endotoxin increases pulmonary vascular protein permeability in the dog

    Energy Technology Data Exchange (ETDEWEB)

    Welsh, C.H.; Dauber, I.M.; Weil, J.V.

    1986-10-01

    Endotoxin increases pulmonary vascular permeability consistently in some species but fails to reliably cause injury in the dog. We wondered whether this phenomenon depended on the method of injury assessment, as others have relied on edema measurement; we quantified injury by monitoring the rate of extravascular protein accumulation. /sup 113m/In-labeled protein and /sup 99m/Tc-labeled erythrocytes were injected into anesthetized dogs and monitored by an externally placed lung probe. A protein leak index, the rate of extravascular protein accumulation, was derived from the rate of increase in lung protein counts corrected for changes in intravascular protein activity. After administration of Salmonella enteriditis endotoxin (4 micrograms/kg), the protein leak index was elevated 2.5-fold (41.1 +/- 4.6 X 10(-4) min-1) compared with control (16.0 +/- 2.8 X 10(-4) min-1). In contrast, wet-to-dry weight ratios failed to increase after endotoxin (4.6 +/- 0.8 vs. control values of 4.2 +/- 0.5 g/g dry bloodless lung). However, we observed that endotoxin increased lung dry weight (per unit body weight), which may have attenuated the change in wet-to-dry weight ratios. To determine whether low microvascular pressures following endotoxin attenuated edema formation, we increased pulmonary arterial wedge pressures in five dogs by saline infusion, which caused an increase in wet-to-dry weight ratios following endotoxin but no change in the five controls. We conclude that low dose endotoxin causes pulmonary vascular protein leak in the dog while edema formation is minimal or absent.

  20. Structural effects of pH and deacylation on surfactant protein C in an organic solvent mixture: a constant-pH MD study.

    Science.gov (United States)

    Carvalheda, Catarina A; Campos, Sara R R; Machuqueiro, Miguel; Baptista, António M

    2013-11-25

    The pulmonary surfactant protein C (SP-C) is a small highly hydrophobic protein that adopts a mainly helical structure while associated with the membrane but misfolds into a β-rich metastable structure upon deacylation, membrane dissociation, and exposure to the neutral pH of the aqueous alveolar subphase, eventually leading to the formation of amyloid aggregates associated with pulmonary alveolar proteinosis. The present constant-pH MD study of the acylated and deacylated isoforms of SP-C in a chloroform/methanol/water mixture, often used to mimic the membrane environment, shows that the loss of the acyl groups has a structural destabilizing effect and that the increase of pH promotes intraprotein contacts which contribute to the loss of helical structure in solution. These contacts result from the poor solvation of charged groups by the solvent mixture, which exhibits a limited membrane-mimetic character. Although a single SP-C molecule was used in the simulations, we propose that analogous intermolecular interactions may play a role in the early stages of the protein misfolding and aggregation in this mixture.

  1. Multiplex protein profiling of bronchoalveolar lavage in idiopathic pulmonary fibrosis and hypersensitivity pneumonitis

    Directory of Open Access Journals (Sweden)

    Willems Stijn

    2013-01-01

    Full Text Available Context: Idiopathic pulmonary fibrosis (IPF and chronic hypersensitivity pneumonitis (HP are diffuse parenchymal lung diseases characterized by a mixture of inflammation and fibrosis, leading to lung destruction and finally death. AIMS: The aim of this study was to compare different pathophysiological mechanisms, such as angiogenesis, coagulation, fibrosis, tissue repair, inflammation, epithelial damage, oxidative stress, and matrix remodeling, in both disorders using bronchoalveolar lavage (BAL. Methods: At diagnosis, patients underwent bronchoscopy with BAL and were divided into three groups: Control ( n = 10, HP ( n = 11, and IPF ( n = 11, based on multidisciplinary approach (clinical examination, radiology, and histology: Multiplex searchlight technology was used to analyze 25 proteins representative for different pathophysiological processes: Eotaxin, basic fibroblast growth factor (FGFb, fibronectin, hepatocyte growth factor (HGF, interleukine (IL-8, IL-12p40, IL-17, IL-23, monocyte chemotactic protein (MCP-1, macrophage-derived chemokine (MDC, myeloperoxidase (MPO, matrix metalloproteinase (MMP-8, MMP-9, active plasminogen activating inhibitor 1 (PAI-1, pulmonary activation regulated chemokine (PARC, placental growth factor (PlGF, protein-C, receptor for advanced glycation end products (RAGE, regulated on activation normal T cells expressed and secreted (RANTES, surfactant protein-C (SP-C, transforming growth factor-β1 (TGF-β1, tissue inhibitor of metalloproteinase-1 (TIMP-1, tissue factor, thymic stromal lymphopoietin (TSLP, and vascular endothelial growth factor (VEGF. Results: All patients suffered from decreased pulmonary function and abnormal BAL cell differential compared with control. Protein levels were increased in both IPF and HP for MMP-8 ( P = 0.022, MMP-9 ( P = 0.0020, MCP-1 ( P = 0.0006, MDC ( P = 0.0048, IL-8 ( P = 0.013, MPO ( P = 0.019, and protein-C ( P = 0.0087, whereas VEGF was decreased ( P = 0.0003 compared with

  2. The Unfolded Protein Response in Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Kelsen, Steven G

    2016-04-01

    Accumulation of nonfunctional and potentially cytotoxic, misfolded proteins in chronic obstructive pulmonary disease (COPD) is believed to contribute to lung cell apoptosis, inflammation, and autophagy. Because of its fundamental role as a quality control system in protein metabolism, the "unfolded protein response" (UPR) is of potential importance in the pathogenesis of COPD. The UPR comprises a series of transcriptional, translational, and post-translational processes that decrease protein synthesis while enhancing protein folding capacity and protein degradation. Several studies have suggested that the UPR contributes to lung cell apoptosis and lung inflammation in at least some subjects with human COPD. However, information on the prevalence of the UPR in subjects with COPD, the lung cells that manifest a UPR, and the role of the UPR in the pathogenesis of COPD is extremely limited and requires additional study.

  3. Surfactant Proteins SP-A and SP-D Modulate Uterine Contractile Events in ULTR Myometrial Cell Line.

    Directory of Open Access Journals (Sweden)

    Georgios Sotiriadis

    Full Text Available Pulmonary surfactant proteins SP-A and SP-D are pattern recognition innate immune molecules. However, there is extrapulmonary existence, especially in the amniotic fluid and at the feto-maternal interface. There is sufficient evidence to suggest that SP-A and SP-D are involved in the initiation of labour. This is of great importance given that preterm birth is associated with increased mortality and morbidity. In this study, we investigated the effects of recombinant forms of SP-A and SP-D (rhSP-A and rhSP-D, the comprising of trimeric lectin domain on contractile events in vitro, using a human myometrial cell line (ULTR as an experimental model. Treatment with rhSP-A or rhSP-D increased the cell velocity, distance travelled and displacement by ULTR cells. rhSP-A and rhSP-D also affected the contractile response of ULTRs when grown on collagen matrices showing reduced surface area. We investigated this effect further by measuring contractility-associated protein (CAP genes. Treatment with rhSP-A and rhSP-D induced expression of oxytocin receptor (OXTR and connexin 43 (CX43. In addition, rhSP-A and rhSP-D were able to induce secretion of GROα and IL-8. rhSP-D also induced the expression of IL-6 and IL-6 Ra. We provide evidence that SP-A and SP-D play a key role in modulating events prior to labour by reconditioning the human myometrium and in inducing CAP genes and pro-inflammatory cytokines thus shifting the uterus from a quiescent state to a contractile one.

  4. Interactions between Surfactants in Solution and Electrospun Protein Fibers: Effects on Release Behavior and Fiber Properties

    DEFF Research Database (Denmark)

    Boutrup Stephansen, Karen; García-Díaz, María; Jessen, Flemming

    2016-01-01

    ), a cationic surfactant (benzalkonium chloride), and a neutral surfactant (Triton X-100) were studied. The anionic surfactants increased the insulin release in a concentration-dependent manner, whereas the neutral surfactant had no significant effect on the release. Interestingly, only minute amounts...... of insulin were released from the fibers when benzalkonium chloride was present. The FSP-Ins fibers appeared dense after incubation with this cationic surfactant, whereas high fiber porosity was observed after incubation with anionic or neutral surfactants. Contact angle measurements and staining...

  5. Surfactant protein D is a candidate biomarker for subclinical tobacco smoke-induced lung damage

    DEFF Research Database (Denmark)

    Johansson, Sofie L.; Tan, Qihua; Holst, René;

    2014-01-01

    Variation in Surfactant Protein D (SP-D) is associated with lung function in tobacco smoke-induced chronic respiratory disease. We hypothesized that the same association exists in the general population and could be used to identify individuals sensitive to smoke-induced lung damage. The associat......Variation in Surfactant Protein D (SP-D) is associated with lung function in tobacco smoke-induced chronic respiratory disease. We hypothesized that the same association exists in the general population and could be used to identify individuals sensitive to smoke-induced lung damage...... or haplotypes, and expiratory lung function were assessed using twin study methodology and mixed-effects models. Significant inverse associations were evident between sSP-D and the forced expiratory volume in 1 second and forced vital capacity in the presence of current tobacco smoking but not in non...... with lung function measures in interaction with tobacco smoking. The obtained data suggest sSP-D as a candidate biomarker in risk assessments for subclinical tobacco smoke-induced lung damage. The data and derived conclusion warrant confirmation in a longitudinal population following chronic obstructive...

  6. Signal amplification in electrochemical detection of buckwheat allergenic protein using field effect transistor biosensor by introduction of anionic surfactant

    Directory of Open Access Journals (Sweden)

    Sho Hideshima

    2016-03-01

    Full Text Available Food allergens, especially buckwheat proteins, sometimes induce anaphylactic shock in patients after ingestion. Development of a simple and rapid screening method based on a field effect transistor (FET biosensor for food allergens in food facilities or products is in demand. In this study, we achieved the FET detection of a buckwheat allergenic protein (BWp16, which is not charged enough to be electrically detected by FET biosensors, by introducing additional negative charges from anionic surfactants to the target proteins. A change in the FET characteristics reflecting surface potential caused by the adsorption of target charged proteins was observed when the target sample was coupled with the anionic surfactant (sodium dodecyl sulfate; SDS, while no significant response was detected without any surfactant treatment. It was suggested that the surfactant conjugated with the protein could be useful for the charge amplification of the target proteins. The surface plasmon resonance analysis revealed that the SDS-coupled proteins were successfully captured by the receptors immobilized on the sensing surface. Additionally, we obtained the FET responses at various concentrations of BWp16 ranging from 1 ng/mL to 10 μg/mL. These results suggest that a signal amplification method for FET biosensing is useful for allergen detection in the food industry.

  7. The effects of GH and hormone replacement therapy on serum concentrations of mannan-binding lectin, surfactant protein D and vitamin D binding protein in Turner syndrome

    DEFF Research Database (Denmark)

    Gravholt, Claus Højbjerg; Leth-Larsen, Rikke; Lauridsen, Anna Lis

    2004-01-01

    function. In the present study we examined whether GH or hormone replacement therapy (HRT) in Turner syndrome (TS) influence the serum concentrations of MBL and two other proteins partaking in the innate immune defence, surfactant protein D (SP-D) and vitamin D binding protein (DBP). DESIGN: Study 1...

  8. Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D

    DEFF Research Database (Denmark)

    Holmskov, U; Mollenhauer, J; Madsen, J

    1999-01-01

    Surfactant protein D (SP-D) is an oligomeric C type lectin that promotes phagocytosis by binding to microbial surface carbohydrates. A 340-kDa glycoprotein (gp-340) has been shown to bind SP-D in the presence of calcium but does so independently of carbohydrate recognition. This protein exists both...... transcription-PCR analysis showed that the main sites of synthesis of gp-340 are lung, trachea, salivary gland, small intestine, and stomach. Immunohistochemistry revealed strong staining for gp-340 in alveolar and other tissue macrophages. Immunostaining of the macrophage membrane was either uniform or focal...... intestine and in the ducts of salivary glands. The distribution of gp-340 in macrophages is compatible with a role as an opsonin receptor for SP-D....

  9. Equilibrium and dynamic interfacial properties of protein/ionic-liquid-type surfactant solutions at the decane/water interface.

    Science.gov (United States)

    Cao, Chong; Lei, Jinmei; Zhang, Lu; Du, Feng-Pei

    2014-11-25

    The interfacial behavior of β-casein and lysozyme solutions has been investigated in the presence of an ionic liquid-type imidazolium surfactant ([C16mim]Br) at the decane/water interface. The dynamic dilational properties of the protein/surfactant solutions are investigated by the oscillating drop method and interfacial tension relaxation method. The interfacial tension isotherms for the mixed adsorption layers indicate that the increased addition of [C16mim]Br to a pure protein changes the properties of the complex formed at the decane/water interface. Whereas the interfacial tension data of the protein/surfactant mixed layers do not clearly show differences with changing bulk composition, the dilational rheology provides undoubted evidence that the structure and, in particular, the dynamics of the adsorbed layers depend on the bulk surfactant concentration. The experiment data for β-casein/[C16mim]Br solutions indicate that at higher bulk [C16mim]Br concentrations, β-casein in the interfacial layer is subject to conformational changes, where it gives space to [C16mim]Br molecules in the form of coadsorb rather than replacement; in contrast, in lysozyme/[C16mim]Br solutions some lysozyme molecules desorb from the interface due to the competitive adsorption of free [C16mim]Br molecules. Experimental results related to the interfacial dilational properties of the protein/surfactant solutions show that the dilational modulus turns out to be more sensitive to the conformation of protein/surfactant mixture at the liquid interface than the interfacial tension.

  10. Persurf, a New Method to Improve Surfactant Delivery: A Study in Surfactant Depleted Rats

    OpenAIRE

    2012-01-01

    PURPOSE: Exogenous surfactant is not very effective in adults with ARDS, since surfactant does not reach atelectatic alveoli. Perfluorocarbons (PFC) can recruit atelectatic areas but do not replace impaired endogenous surfactant. A surfactant-PFC-mixture could combine benefits of both therapies. The aim of the proof-of-principal-study was to produce a PFC-in-surfactant emulsion (Persurf) and to test in surfactant depleted Wistar rats whether Persurf achieves I.) a more homogenous pulmonary di...

  11. Surfactant protein D binds to human immunodeficiency virus (HIV) envelope protein gp120 and inhibits HIV replication

    DEFF Research Database (Denmark)

    Meschi, Joseph; Crouch, Erika C; Skolnik, Paul;

    2005-01-01

    The envelope protein (gp120) of human immunodeficiency virus (HIV) contains highly conserved mannosylated oligosaccharides. These glycoconjugates contribute to resistance to antibody neutralization, and binding to cell surface lectins on macrophages and dendritic cells. Mannose-binding lectin (MBL......) binds to gp120 and plays a role in defence against the virus. In this study it is demonstrated that surfactant protein D (SP-D) binds to gp120 and inhibits HIV infectivity at significantly lower concentrations than MBL. The binding of SP-D was mediated by its calcium-dependent carbohydrate...... defence against HIV. A chimeric protein containing the N-terminal and collagen domains of SP-D linked to the neck and carbohydrate-recognition domains of MBL (called SP-D/MBL(neck+CRD)) had greater ability to bind to gp120 and inhibit virus replication than either SP-D or MBL. The enhanced binding of SP...

  12. Distribution of endotracheally instilled surfactant protein SP-C in lung-lavaged rabbits.

    NARCIS (Netherlands)

    Bambang Oetomo, Sidarto; de Leij, Louis; Curstedt, T; ter Haar, J G; Schoots, Coenraad; Wildevuur, Charles; Okken, Albert

    1991-01-01

    In lung-lavaged surfactant-deficient rabbits (n = 6) requiring artificial ventilation, porcine surfactant was instilled endotracheally. This resulted in improvement of lung function so that the animals could be weaned off artificial ventilation. The animals were killed 4 1/2 h after surfactant admin

  13. Small surfactant-like peptides can drive soluble proteins into active aggregates

    Directory of Open Access Journals (Sweden)

    Zhou Bihong

    2012-01-01

    Full Text Available Abstract Background Inactive protein inclusion bodies occur commonly in Escherichia coli (E. coli cells expressing heterologous proteins. Previously several independent groups have found that active protein aggregates or pseudo inclusion bodies can be induced by a fusion partner such as a cellulose binding domain from Clostridium cellulovorans (CBDclos when expressed in E. coli. More recently we further showed that a short amphipathic helical octadecapeptide 18A (EWLKAFYEKVLEKLKELF and a short beta structure peptide ELK16 (LELELKLKLELELKLK have a similar property. Results In this work, we explored a third type of peptides, surfactant-like peptides, for performing such a "pulling-down" function. One or more of three such peptides (L6KD, L6K2, DKL6 were fused to the carboxyl termini of model proteins including Aspergillus fumigatus amadoriase II (AMA, all three peptides were used, Bacillus subtilis lipase A (LipA, only L6KD was used, hereinafter the same, Bacillus pumilus xylosidase (XynB, and green fluorescent protein (GFP, and expressed in E. coli. All fusions were found to predominantly accumulate in the insoluble fractions, with specific activities ranging from 25% to 92% of the native counterparts. Transmission electron microscopic (TEM and confocal fluorescence microscopic analyses confirmed the formation of protein aggregates in the cell. Furthermore, binding assays with amyloid-specific dyes (thioflavin T and Cong red to the AMA-L6KD aggregate and the TEM analysis of the aggregate following digestion with protease K suggested that the AMA-L6KD aggregate may contain structures reminiscent of amyloids, including a fibril-like structure core. Conclusions This study shows that the surfactant-like peptides L6KD and it derivatives can act as a pull-down handler for converting soluble proteins into active aggregates, much like 18A and ELK16. These peptide-mediated protein aggregations might have important implications for protein aggregation in

  14. Energy and Protein Intake and Its Relationship with Pulmonary Function in Chronic Obstructive Pulmonary Disease (COPD Patients

    Directory of Open Access Journals (Sweden)

    Leila Yazdanpanah

    2010-12-01

    Full Text Available Chronic Obstructive Pulmonary Disease (COPD is a public health problem worldwide. Increased energy and protein needs, decreased energy and protein intake are common in COPD patients. Adequate intake is essential to improve pulmonary function and immune system, prevention of weight loss and maintaining muscle mass and strength. Assessment of energy and protein intake and its relationship with pulmonary function in COPD patients was performed in this study. The study group included 63 COPD patients. For all subjects, evaluation of energy and protein intake by Food Frequency Questionnaire (FFQ and 24-hour recall, spirometry for measuring pulmonary function and determining disease severity were performed. The subjects were divided into three groups based on disease severity according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD stages. Relationship between energy and protein intake with pulmonary function was assessed. Energy and protein intake were lower than the calculated energy and protein demand for all groups. Significant relationship was found between the amount of protein intake extrapolated from food frequency questionnaire with Forced Vital Capacity (FVC (r=0.2, P=0.02 and Vital Capacity (VC (r=0.3, P=0.008. The results of the study suggest that accurate evaluation of protein and energy intake and requirements should be included in the goals of medical treatment of COPD patients.

  15. Pilot study exploring lung allograft surfactant protein A (SP-A) expression in association with lung transplant outcome.

    Science.gov (United States)

    D'Ovidio, F; Kaneda, H; Chaparro, C; Mura, M; Lederer, D; Di Angelo, S; Takahashi, H; Gutierrez, C; Hutcheon, M; Singer, L G; Waddell, T K; Floros, J; Liu, M; Keshavjee, S

    2013-10-01

    Primary graft failure and chronic lung allograft dysfunction (CLAD) limit lung transplant long-term outcomes. Various lung diseases have been correlated with surfactant protein (SP) expression and polymorphisms. We sought to investigate the role of SP expression in lung allografts prior to implantation, in relation to posttransplant outcomes. The expression of SP-(A, B, C, D) mRNA was assayed in 42 allografts. Posttransplant assessments include pulmonary function tests, bronchoscopy, broncho-alveolar lavage fluid (BALF) and biopsies to determine allograft rejection. BALF was assayed for SP-A, SP-D in addition to cytokines IL-8, IL-12 and IL-2. The diagnosis of CLAD was evaluated 6 months after transplantation. Lung allografts with low SP-A mRNA expression prior to implantation reduced survival (Log-rank p < 0.0001). No association was noted for the other SPs. Allografts with low SP-A mRNA had greater IL-2 (p = 0.03) and IL-12 (p < 0.0001) in the BALF and a greater incidence of rejection episodes (p = 0.003). Levels of SP-A mRNA expression were associated with the SP-A2 polymorphisms (p = 0.015). Specifically, genotype 1A1A(0) was associated with lower SP-A mRNA expression (p < 0.05). Lung allografts with low levels of SP-A mRNA expression are associated with reduced survival. Lung allograft SP-A mRNA expression appears to be associated with SP-A gene polymorphisms.

  16. Surfactant protein d deficiency in mice is associated with hyperphagia, altered fat deposition, insulin resistance, and increased basal endotoxemia.

    Directory of Open Access Journals (Sweden)

    Jacob V Stidsen

    Full Text Available Pulmonary surfactant protein D (SP-D is a host defence lectin of the innate immune system that enhances clearance of pathogens and modulates inflammatory responses. Recently it has been found that systemic SP-D is associated with metabolic disturbances and that SP-D deficient mice are mildly obese. However, the mechanism behind SP-D's role in energy metabolism is not known.Here we report that SP-D deficient mice had significantly higher ad libitum energy intake compared to wild-type mice and unchanged energy expenditure. This resulted in accumulation but also redistribution of fat tissue. Blood pressure was unchanged. The change in energy intake was unrelated to the basal levels of hypothalamic Pro-opiomelanocortin (POMC and Agouti-related peptide (AgRP gene expression. Neither short time systemic, nor intracereberoventricular SP-D treatment altered the hypothalamic signalling or body weight accumulation.In ad libitum fed animals, serum leptin, insulin, and glucose were significantly increased in mice deficient in SP-D, and indicative of insulin resistance. However, restricted diets eliminated all metabolic differences except the distribution of body fat. SP-D deficiency was further associated with elevated levels of systemic bacterial lipopolysaccharide.In conclusion, our findings suggest that lack of SP-D mediates modulation of food intake not directly involving hypothalamic regulatory pathways. The resulting accumulation of adipose tissue was associated with insulin resistance. The data suggest SP-D as a regulator of energy intake and body composition and an inhibitor of metabolic endotoxemia. SP-D may play a causal role at the crossroads of inflammation, obesity, and insulin resistance.

  17. Environmental Pollutant Ozone Causes Damage to Lung Surfactant Protein B (SP-B)

    Science.gov (United States)

    2015-01-01

    Lung surfactant protein B (SP-B) is an essential protein found in the surfactant fluid at the air–water interface of the lung. Exposure to the air pollutant ozone could potentially damage SP-B and lead to respiratory distress. We have studied two peptides, one consisting of the N-terminus of SP-B [SP-B(1–25)] and the other a construct of the N- and C-termini of SP-B [SP-B(1–25,63–78)], called SMB. Exposure to dilute levels of ozone (∼2 ppm) of monolayers of each peptide at the air–water interface leads to a rapid reaction, which is evident from an increase in the surface tension. Fluorescence experiments revealed that this increase in surface tension is accompanied by a loss of fluorescence from the tryptophan residue at the interface. Neutron and X-ray reflectivity experiments show that, in contrast to suggestions in the literature, the peptides are not solubilized upon oxidation but rather remain at the interface with little change in their hydration. Analysis of the product material reveals that no cleavage of the peptides occurs, but a more hydrophobic product is slowly formed together with an increased level of oligomerization. We attributed this to partial unfolding of the peptides. Experiments conducted in the presence of phospholipids reveal that the presence of the lipids does not prevent oxidation of the peptides. Our results strongly suggest that exposure to low levels of ozone gas will damage SP-B, leading to a change in its structure. The implication is that the oxidized protein will be impaired in its ability to interact at the air–water interface with negatively charged phosphoglycerol lipids, thus compromising what is thought to be its main biological function. PMID:26270023

  18. Prognostic value of immunohistochemical surfactant protein A expression in regenerative/hyperplastic alveolar epithelial cells in idiopathic interstitial pneumonias

    Directory of Open Access Journals (Sweden)

    Kajiki Akira

    2011-03-01

    Full Text Available Abstract Background It is difficult to predict survival in patients with idiopathic pulmonary fibrosis. Recently, several proteins, such as surfactant protein (SP and KL-6, have been reported to be useful biologic markers for prediction of prognosis for interstitial pneumonias. It is not clear whether there is any relationship between expression of these proteins in regenerative/hyperplastic alveolar epithelial cells and prognosis of idiopathic interstitial pneumonias (IIPs. Objectives This study aimed to elucidate the clinical significance of the expression of such lung secretory proteins as SP-A and KL-6 in lung tissues of patients with IIPs. Methods We retrospectively investigated the immunohistochemical expression of SP-A, KL-6, cytokeratin (CK, and epithelial membrane antigen (EMA in alveolar epithelial cells in lung tissues obtained from surgical lung biopsy in 43 patients with IIPs, and analyzed the correlation between expression of these markers and the prognosis of each IIP patient. CK and EMA were used as general markers for epithelial cells. Results In patients with usual interstitial pneumonia (UIP, the ratio of SP-A positive epithelial cells to all alveolar epithelial cells (SP-A positive ratio in the collapsed and mural fibrosis areas varied, ranging from cases where almost all alveolar epithelial cells expressed SP-A to cases where only a few did. On the other hand, in many patients with nonspecific interstitial pneumonia (NSIP, many of the alveolar epithelial cells in the diseased areas expressed SP-A. The SP-A positive ratio was significantly lower in patients who died from progression of UIP than in patients with UIP who remained stable or deteriorated but did not die. In NSIP patients, a similar tendency was noted between the SP-A positive ratio and prognosis. Conclusions The results suggest that the paucity of immunohistochemical SP-A expression in alveolar epithelial cells in diseased areas (i.e. regenerative

  19. Pulmonary surfactant expression analysis--role of cell-cell interactions and 3-D tissue-like architecture.

    Science.gov (United States)

    Nandkumar, Maya A; Ashna, U; Thomas, Lynda V; Nair, Prabha D

    2015-03-01

    Surfactant production is important in maintaining alveolar function both in vivo and in vitro, but surfactant expression is the primary property lost by alveolar Type II Pneumocytes in culture and its maintenance is a functional requirement. To develop a functional tissue-like model, the in vivo cell-cell interactions and three dimensional architecture has to be reproduced. To this end, 3D button-shaped synthetic gelatin vinyl acetate (GeVAc) co-polymer scaffold was seeded with different types of lung cells. Functionality of the construct was studied under both static and dynamic conditions. The construct was characterized by Environmental Scanning Electron and fluorescent microscopy, and functionality of the system was analyzed by studying mRNA modulations of all four surfactant genes A, B, C, and D by real time-PCR and varying culture conditions. The scaffold supports alveolar cell adhesion and maintenance of cuboidal morphology, and the alveolar-specific property of surfactant synthesis, which would otherwise be rapidly lost in culture. This is a novel 3D system that expresses all 4 surfactants for a culture duration of 3 weeks.

  20. Serial bronchoscopic lung lavage in pulmonary alveolar proteinosis under local anesthesia

    Directory of Open Access Journals (Sweden)

    K Rennis Davis

    2015-01-01

    Full Text Available Pulmonary alveolar proteinosis (PAP is a rare disease, characterized by alveolar accumulation of surfactant composed of proteins and lipids due to defective surfactant clearance by alveolar macrophages. Mainstay of treatment is whole lung lavage, which requires general anesthesia. Herein, we report a case of primary PAP, successfully treated with serial bronchoscopic lung lavages under local anesthesia.

  1. Association between the surfactant protein D (SFTPD) gene and subclinical carotid artery atherosclerosis

    DEFF Research Database (Denmark)

    Sorensen, Grith L; Bladbjerg, Else Marie; Steffensen, Rudi;

    2016-01-01

    OBJECTIVE: Surfactant protein D (SP-D) is a defense collectin with inflammation-modulating properties. SP-D deficiency inhibits atherosclerosis in vivo, and the circulatory SP-D levels have been previously associated with cardiovascular disease mortality. We hypothesized that plasma SP-D (p......SP-D) and SP-D gene (SFTPD) single nucleotide polymorphisms (SNPs) are risk factors for atherosclerosis. METHODS: We evaluated individuals who were all 60 years old and participated in The Glostrup Population Study. Subclinical atherosclerosis was diagnosed based on the ultrasonographic measurement of intima......: The results do not support that pSP-D levels influence the development of subclinical atherosclerosis. However, the SFTPD SNP data support previous observations from animal studies that SP-D plays a role in the etiology of atherosclerotic disease development. The nominal significant effects are likely...

  2. Protein losing enteropathy secondary to a pulmonary artery stent

    Directory of Open Access Journals (Sweden)

    Narayanswami Sreeram

    2012-01-01

    Full Text Available A 2-year-old patient with hypoplastic left heart syndrome presented 6 months following Fontan completion with protein-losing enteropathy (PLE. He had undergone stent implantation in the left pulmonary artery after the Norwood procedure, followed by redilation of the stent prior to Fontan completion. Combined bronchoscopic and catheterization studies during spontaneous breathing confirmed left bronchial stenosis behind the stent, and diastolic systemic ventricular pressure during expiration of 25 mm Hg. We postulate that the stent acts as a valve, against which the patient generates high expiratory pressures, which are reflected in the ventricular diastolic pressure. This may be the cause of PLE.

  3. Involvement of eicosanoids and surfactant protein D in extrinsic allergic alveolitis.

    Science.gov (United States)

    Higashi, A; Higashi, N; Tsuburai, T; Takeuchi, Y; Taniguchi, M; Mita, H; Saito, A; Takatori, K; Arimura, K; Akiyama, K

    2005-12-01

    The pathophysiology of extrinsic allergic alveolitis (EAA) involves oxidative lung damage as well as interstitial and alveolar inflammation. Macrophages and mast cells are inflammatory components of EAA that produce both leukotrienes (LTs) and prostaglandin D2 (PGD2). In addition, PGD2 is also produced by the free-radical-catalysed peroxidation of arachidonic acid during oxidative stress. Urinary 8-iso prostaglandin F2alpha (8-isoPGF2alpha) and serum surfactant protein D (SP-D) are considered appropriate biomarkers of oxidative stress and interstitial lung disease activity, respectively. The present study aimed to assess the association of these biomarkers with the pathophysiology of EAA. Two cases of acute EAA caused by the inhalation of fungi spores were reported. Eight asthmatic patients and six healthy control subjects were also enrolled in the current study. The serum SP-D and urinary eicosanoid (LTE4, PGD2 metabolite (9alpha,11betaPGF2), 8-isoPGF2alpha) concentrations markedly increased during the acute exacerbation phase. These concentrations decreased following corticosteroid therapy in the EAA patients. There was a significant correlation between serum SP-D and urinary 9alpha,11betaPGF2 concentrations in the EAA patients. In conclusion, although the present study proposes that serum surfactant protein-D and urinary eicosanoids are new biomarkers involved in the various immunological responses in extrinsic allergic alveolitis, further large-scale studies are needed to investigate the role of these compounds, not just as biomarkers, but also as biological potentiators of extrinsic allergic alveolitis.

  4. Measurement of human surfactant protein-B turnover in vivo from tracheal aspirates using targeted proteomics.

    Science.gov (United States)

    Tomazela, Daniela M; Patterson, Bruce W; Hanson, Elizabeth; Spence, Kimberly L; Kanion, Tiffany B; Salinger, David H; Vicini, Paolo; Barret, Hugh; Heins, Hillary B; Cole, F Sessions; Hamvas, Aaron; MacCoss, Michael J

    2010-03-15

    We describe a method to measure protein synthesis and catabolism in humans without prior purification and use the method to measure the turnover of surfactant protein-B (SP-B). SP-B, a lung-specific, hydrophobic protein essential for fetal-neonatal respiratory transition, is present in only picomolar quantities in tracheal aspirate samples and difficult to isolate for dynamic turnover studies using traditional in vivo tracer techniques. Using infusion of [5,5,5-(2)H(3)] leucine and a targeted proteomics method, we measured both the quantity and kinetics of SP-B tryptic peptides in tracheal aspirate samples of symptomatic newborn infants. The fractional synthetic rate (FSR) of SP-B measured using the most abundant proteolytic fragment, a 10 amino acid peptide from the carboxy-terminus of proSP-B (SPTGEWLPR), from the circulating leucine pool was 0.035 +/- 0.005 h(-1), and the fractional catabolic rate was 0.044 +/- 0.003 h(-1). This technique permits high-throughput and sensitive measurement of turnover of low abundance proteins with minimal sample preparation.

  5. Surfactant protein-A modulates LPS-induced TLR4 localization and signaling via β-arrestin 2.

    Directory of Open Access Journals (Sweden)

    Vicky Sender

    Full Text Available The soluble C-type lectin surfactant protein (SP-A mediates lung immune responses partially via its direct effects on alveolar macrophages (AM, the main resident leukocytes exposed to antigens. SP-A modulates the AM threshold of lipopolysaccharide (LPS activity towards an anti-inflammatory phenotype both in vitro and in vivo through various mechanisms. LPS responses are tightly regulated via distinct pathways including subcellular TLR4 localization and thus ligand sensing. The cytosolic scaffold and signaling protein β-arrestin 2 acts as negative regulator of LPS-induced TLR4 activation. Here we show that SP-A neither increases TLR4 abundancy nor co-localizes with TLR4 in primary AM. SP-A significantly reduces the LPS-induced co-localization of TLR4 with the early endosome antigen (EEA 1 by promoting the co-localization of TLR4 with the post-Golgi compartment marker Vti1b in freshly isolated AM from rats and wild-type (WT mice, but not in β-arrestin 2(-/- AM. Compared to WT mice pulmonary LPS-induced TNF-α release in β-arrestin 2(-/- mice is accelerated and enhanced and exogenous SP-A fails to inhibit both lung LPS-induced TNF-α release and TLR4/EEA1 positioning. SP-A, but not LPS, enhances β-arrestin 2 protein expression in a time-dependent manner in primary rat AM. The constitutive expression of β-arrestin 2 in AM from SP-A(-/- mice is significantly reduced compared to SP-A(+/+ mice and is rescued by SP-A. Prolonged endosome retention of LPS-induced TLR4 in AM from SP-A(-/- mice is restored by exogenous SP-A, and is antagonized by β-arrestin 2 blocking peptides. LPS induces β-arrestin 2/TLR4 association in primary AM which is further enhanced by SP-A. The data demonstrate that SP-A modulates LPS-induced TLR4 trafficking and signaling in vitro and in vivo engaging β-arrestin 2.

  6. Surfactant inhibition in acute respiratory failure : consequences for exogenous surfactant therapy

    NARCIS (Netherlands)

    E.P. Eijking (Eric)

    1993-01-01

    textabstractThe neonatal respiratory distress syndrome (RDS) is characterized by immaturity of the lung, resulting in relative or absolute absence of pulmonary surfactant. Worldwide, neonates suffering from RDS have been treated successfully with exogenous surfactant preparations. Currently, exogeno

  7. [The phenol turbidity test for measurement of pulmonary surfactants in amniotic fluid--rapid test for fetal lung maturity (author's transl)].

    Science.gov (United States)

    Tatsumi, H; Shimada, N; Kuramoto, R; Mochizuki, Y; Nishizima, M; Arai, M; Osanai, K; Ishihara, K; Goso, K; Hotta, K

    1981-05-01

    A simple and sensitive procedure for the quantitative estimation of pulmonary surfactants in the amniotic fluid is described. The method is based on the formation of turbidity from the amniotic fluid surfactants with phenol. Amniotic fluid drawn through an intrauterine catheter was centrifuged at 2000 rpm for 5 min. One ml of 5% aqueous phenol solution was added to 1.0 ml of the diluted supernatant. Control solution was prepared by addition of 1.0 ml of distilled water to the supernatant, instead of phenol solution. The turbidity was measured spectrophotometrically against control at 340 nm 5 to 10 min after agitation on a Vortex mixer for 5 sec. The turbidity obtained from amniotic fluid with phenol was proportional to the increase in total phospholipids in the fluid measured enzymatically. Moreover, only lecithin in the phospholipids was related to the turbidity formation. Sphyngomyelin, lysolecithin, phosphatidylethanolamin did not produce any turbidity with phenol. The spectrophotometric reading of 87 cases (31-41 weeks) was ranged at 0.18-3.52. Four cases with lower value (0.40) showed neonatal respiratory problem. The phenol turbidity test is more useful for the detection of fetal lung maturity comparing with the generally used shake test.

  8. Effect of surfactants on Ra-sHSPI - A small heat shock protein from the cattle tick Rhipicephalus annulatus

    Science.gov (United States)

    Siddiqi, Mohammad Khursheed; Shahein, Yasser E.; Hussein, Nahla; Khan, Rizwan H.

    2016-09-01

    Electrostatic interaction plays an important role in protein aggregation phenomenon. In this study, we have checked the effect of anionic - Sodium Dodecyl Sulfate (SDS) and cationic-Cetyltrimethyl Ammonium Bromide (CTAB) surfactant on aggregation behavior of Ra-sHSPI, a small heat shock protein purified from Rhipicephalus annulatus tick. To monitor the effect of these surfactants, we have employed several spectroscopic methods such as Rayleigh light scattering measurements, ANS (8-Anilinonaphthalene-1-sulfonic acid) fluorescence measurements, ThT (Thioflavin T) binding assays, Far-UV CD (Circular Dichroism) and dynamic light scattering measurements. In the presence of anionic surfactant-SDS, Ra-sHSPI forms amyloid fibrils, in contrast, no amyloid formation was observed in presence of cationic surfactant at low pH. Enhancement of ANS fluorescence intensity confirms the exposition of more hydrophobic patches during aggregation. ThT binding assay confirms the amyloid fibrillar nature of the SDS induced Ra-sHSPI aggregates and supported by PASTA 2.0 (prediction of amyloid structural aggregation) software. This study demonstrates the crucial role of charge during amyloid fibril formation at low pH in Ra-sHSPI.

  9. Interaction of surfactant protein A with the intermediate filaments desmin and vimentin.

    Science.gov (United States)

    Garcia-Verdugo, Ignacio; Synguelakis, Monique; Degrouard, Jeril; Franco, Claudio-Areias; Valot, Benoit; Zivy, Michel; Chaby, Richard; Tanfin, Zahra

    2008-05-06

    Surfactant protein A (SP-A), a member of the collectin family that modulates innate immunity, has recently been involved in the physiology of reproduction. Consistent with the activation of ERK-1/2 and COX-2 induced by SP-A in myometrial cells, we reported previously the presence of two major proteins recognized by SP-A in these cells. Here we identify by mass spectrometry one of these SP-A targets as the intermediate filament (IF) desmin. In myometrial preparations derived from desmin-deficient mice, the absence of binding of SP-A to any 50 kDa protein confirmed the identity of this SP-A-binding site as desmin. Our data based on partial chymotrypsin digestion of pure desmin suggested that SP-A recognizes especially its rod domain, which is known to play an important role during the assembly of desmin into filaments. In line with that, electron microscopy experiments showed that SP-A inhibits in vitro the polymerization of desmin filaments. SP-A also recognized in vitro polymerized filaments in a calcium-dependent manner at a physiological ionic strength but not the C1q receptor gC1qR. Furthermore, Texas Red-labeled SP-A colocalized with desmin filaments in myometrial cells. Interestingly, vimentin, the IF characteristic of leukocytes, is one of the major proteins recognized by SP-A in protein extracts of U937 cells after PMA-induced differentiation of this monocytic cell line. Interaction of SP-A with vimentin was further confirmed using recombinant vimentin in solid-phase binding assays. The ability of SP-A to interact with desmin and vimentin, and to prevent polymerization of desmin monomers, shed light on unexpected and wider biological roles of this collectin.

  10. AMOTL2 interaction with TAZ causes the inhibition of surfactant proteins expression in lung cells.

    Science.gov (United States)

    Lucci, Valeria; Di Palma, Tina; D'Ambrosio, Chiara; Scaloni, Andrea; Zannini, Mariastella

    2013-10-25

    TAZ (Transcriptional co-Activator with PDZ-binding motif), is a biologically potent transcriptional coactivator and functions by binding to the PPXY motif present in several transcription factors. Notably, TAZ behaves as a transducer linking cytoplasmic signaling events to transcriptional regulation in the nucleus. Several different factors regulate TAZ expression and/or function. In particular, a major regulation of TAZ activity occurs through the Hippo pathway by a phosphorylation-mediated mechanism that causes its cytoplasmic sequestration or degradation. Here we demonstrate that AMOTL2 robustly co-immunoprecipitates with TAZ, and their interaction is dependent on the WW domain of TAZ and the PPXY motif in the N-terminus of AMOTL2. Furthermore, we show that AMOTL2 colocalizes with TAZ in the cytoplasm of H441 human lung cells and regulates TAZ cytoplasm-to-nucleus translocation through direct protein-protein interaction. Interestingly, the overexpression of AMOTL2 inhibits the functional cooperation between the transcription factor TTF-1 and TAZ on the Surfactant C gene promoter, as well as the expression of other known target genes of these regulatory factors. Taken together, our results suggest an inhibitory role of AMOTL2 on TAZ ability to co-activate transcription and describe a different mechanism, Hippo pathway-independent, that modulates the activity of TAZ in lung cells through the interaction with Angiomotin-like 2 (AMOTL2). © 2013 Elsevier B.V. All rights reserved.

  11. Surfactant protein A regulates IgG-mediated phagocytosis in inflammatory neutrophils.

    Science.gov (United States)

    Wofford, Jessica A; Wright, Jo Rae

    2007-12-01

    Surfactant proteins (SP)-A and SP-D have been shown to affect the functions of a variety of innate immune cells and to interact with various immune proteins such as complement and immunoglobulins. The goal of the current study is to test the hypothesis that SP-A regulates IgG-mediated phagocytosis by neutrophils, which are major effector cells of the innate immune response that remove invading pathogens by phagocytosis and by extracellular killing mediated by reactive oxygen and nitrogen. We have previously shown that SP-A stimulates chemotaxis by inflammatory, but not peripheral, neutrophils. To evaluate the ability of SP-A to modulate IgG-mediated phagocytosis, polystyrene beads were coated with BSA and treated with anti-BSA IgG. SP-A significantly and specifically enhanced IgG-mediated phagocytosis by inflammatory neutrophils, but it had no effect on beads not treated with IgG. SP-A bound to IgG-coated beads and enhanced their uptake via direct interactions with the beads as well as direct interactions with the neutrophils. SP-A did not affect reactive oxygen production or binding of IgG to neutrophils and had modest effects on polymerization of actin. These data suggest that SP-A plays an important role in mediating the phagocytic response of neutrophils to IgG-opsonized particles.

  12. Preparation of Mesoporous Nano-Hydroxyapatite Using a Surfactant Template Method for Protein Delivery

    Institute of Scientific and Technical Information of China (English)

    Xiaodong Wu; Xiaofeng Song; Dongsong Li; Jianguo Liu; Peibiao Zhang; Xuesi Chen

    2012-01-01

    Mesoporous nano-hydroxyapatite (n-HA) has gained more and more attention as drug storage and release hosts.The aim of this study is to observe the effect of the ratio of surfactant to the theoretical yield of HA on the mesoporous n-HA,then to reveal the effect of the mesoporous nanostrueture on protein delivery.The mesoporous n-HA was synthesized using the wet precipitation in the presence of cetyltrimethylammonium bromide (CTAB) at ambient temperature and normal atmospheric pressure.The morphology,size,crystalline phase,chemical composition and textural characteristics of the product were well characterized by X-ray Powder Diffraction (XRD),Fourier Transform Infrared Spectroscopy (FTIR),Scanning Electron Microscopy (SEM),Transmission Electron Microscopy (TEM),Dynamic Light Scattering (DLS) and N2 adsorption/desorption,respectively.The protein adsorption/release studies were also carried out by using Bovine Serum Albumin (BSA) as a model protein.The results reveal that the mesoporous n-HA synthesized with CTAB exhibits high pure phase,low crystallinity and the typical characteristics of the mesostructure.The BSA loading increases with the specific surface area and the pore volume of n-HA,and the release rates of BSA are different due to their different pore sizes and pore structures,n-HA synthesized with 0.5% CTAB has the highest BSA loading and the slowest release rate because of its highest surface area and smaller pore size.These mesoporous n-HA materials demonstrate a potential application in the field of protein delivery due to their bioaetive,biocompatible and mesoporous properties.

  13. Certain surfactants significantly enhance the activity of antibiotics in the mouse model of MTB and drug resistant MTB infection and effectively remove the bacteria from a pulmonary cavity in human ex-vivo study.

    Science.gov (United States)

    Risin, Semyon A; Hunter, Robert L; Kobak, Mikhail; Ariel, Boris; Vishnevsky, Boris; Erokhin, Vladislav; Demikhova, Olga; Bocharova, Irina; Stoops, James K

    2014-01-01

    Surfactants have the potential to overcome natural resistance of MTB to antibiotics which is mediated by barriers that impede the penetration of drugs to their targets. A major component of this barrier is trehalose dimycolate (TDM) which surrounds the bacteria with a thick lipid shield. In this study dodecyl maltoside (DDM) was evaluated for this purpose. This surfactant is an excellent cellular permeabilizing agent with associated low toxicity. The administration of the surfactant as an aerosol into the lungs of the infected mice achieved a 5-10 times enhancement of the isoniazid (INH) treatment gauged by the reduction of the colony forming units. This study also established proof of principle that surfactants alone applied as an aerosol can reduce the bacteria count in lungs infected with MTB. The potential of the surfactant in the therapy of human cavitary TB was also investigated using a surgically removed lung from a patient with extreme drug resistant MTB (XDR-TB). A cavity in this lung was flushed with DDM solution ex-vivo. The procedure readily removed the bacteria, excessive amounts of TDM and necrotic tissue from the cavity. These studies demonstrate that DDM can disrupt the layers of TDM and free embedded MTB and, consequently, surfactants have promise as a proficient modality for the treatment of pulmonary MTB.

  14. Protein aggregation with poly(vinyl) alcohol surfactant reduces double emulsion-encapsulated mammalian cell-free expression

    Science.gov (United States)

    Ho, Kenneth K. Y.; Lee, Jin Woo; Durand, Grégory; Majumder, Sagardip

    2017-01-01

    Development of artificial cell models requires encapsulation of biomolecules within membrane-bound compartments. There have been limited studies of using mammalian cell-free expression (CFE) system as the ‘cytosol’ of artificial cells. We exploit glass capillary droplet microfluidics for the encapsulation of mammalian CFE within double emulsion templated vesicles. The complexity of the physicochemical properties of HeLa cell-free lysate poses a challenge compared with encapsulating simple buffer solutions. In particular, we discovered the formation of aggregates in double emulsion templated vesicles encapsulating mammalian HeLa CFE, but not with bacterial CFE. The aggregates did not arise from insolubility of the proteins made from CFE nor due to the interaction of mammalian CFE with the organic solvents in the middle phase of the double emulsions. We found that aggregation is dependent on the concentration of poly(vinyl) alcohol (PVA) surfactant, a critical double emulsion-stabilizing surfactant, and the lysate concentration in mammalian CFE. Despite vesicle instability and reduced protein expression, we demonstrate protein expression by encapsulating mammalian CFE system. Using mass spectrometry and Western blot, we identified and verified that actin is one of the proteins inside the mammalian CFE that aggregated with PVA surfactant. Our work establishes a baseline description of mammalian CFE system encapsulated in double emulsion templated vesicles as a platform for building artificial cells. PMID:28358875

  15. Protein aggregation with poly(vinyl) alcohol surfactant reduces double emulsion-encapsulated mammalian cell-free expression.

    Science.gov (United States)

    Ho, Kenneth K Y; Lee, Jin Woo; Durand, Grégory; Majumder, Sagardip; Liu, Allen P

    2017-01-01

    Development of artificial cell models requires encapsulation of biomolecules within membrane-bound compartments. There have been limited studies of using mammalian cell-free expression (CFE) system as the 'cytosol' of artificial cells. We exploit glass capillary droplet microfluidics for the encapsulation of mammalian CFE within double emulsion templated vesicles. The complexity of the physicochemical properties of HeLa cell-free lysate poses a challenge compared with encapsulating simple buffer solutions. In particular, we discovered the formation of aggregates in double emulsion templated vesicles encapsulating mammalian HeLa CFE, but not with bacterial CFE. The aggregates did not arise from insolubility of the proteins made from CFE nor due to the interaction of mammalian CFE with the organic solvents in the middle phase of the double emulsions. We found that aggregation is dependent on the concentration of poly(vinyl) alcohol (PVA) surfactant, a critical double emulsion-stabilizing surfactant, and the lysate concentration in mammalian CFE. Despite vesicle instability and reduced protein expression, we demonstrate protein expression by encapsulating mammalian CFE system. Using mass spectrometry and Western blot, we identified and verified that actin is one of the proteins inside the mammalian CFE that aggregated with PVA surfactant. Our work establishes a baseline description of mammalian CFE system encapsulated in double emulsion templated vesicles as a platform for building artificial cells.

  16. Effect of pulmonary surfactant and phospholipid hexadecanol tyloxapol on recombinant human-insulin absorption from intratracheally administered dry powders in diabetic rats.

    Science.gov (United States)

    Zheng, Jianheng; Zhang, Ge; Lu, Yang; Fang, Fang; He, Jiake; Li, Ning; Talbi, Amer; Zhang, Ying; Tang, Yue; Zhu, Jiabi; Chen, Xijing

    2010-12-01

    The purpose of the present study was to evaluate the enhancement effect of the natural pulmonary surfactant (PS) or its artificial substitute, phospholipid hexadecanol tyloxapol (PHT) on the bioavailability and hypoglycemic activity of recombinant human insulin (rh-insulin) in a pulmonary delivery system. PS- or PHT-loaded insulin formulation was administered to streptozotocin induced diabetic rats, at doses of 5 U/kg, 10 U/kg and 20 U/kg insulin, respectively. The hypoglycemic effect caused by PS or PHT containing rh-insulin was analyzed and the area above the curves (AAC) of serum glucose levels versus time, the minimum glucose concentration (C(min)), the time to C(min) (T(min)) and the pharmacological availability (PA%) were derived from the serum glucose profiles. Results showed that PS and PHT caused significantly decrease in serum glucose levels. The decrease in plasma glucose levels continued for about 5 h after the nadir. The highest AAC value was obtained when 20 U/kg rh-insulin with PS or PHT as absorption enhancer was administered to rats. AAC(0-360 min) of PS- or PHT-loaded rh-insulin was 2-3 times as much as that without PS or PHT and PA% increased by 1.3-2 fold. Thus, the extent of oral absorption of insulin from PS- or PHT-loaded particles was significantly greater when compared with that without them. In addition, PHT as well as PS did not change the lactate dehydrogenase (LDH) activity, alkaline phosphatase (AKP) activity and N-acetyl-β-D-glucoaminidase (NAG) activity in bronch fluid which are sensitive indicators of acute toxicity to lung cells in bronchoalveolar lavage (BAL). It is concluded that PS and PHT is a promising absorption enhancer for pulmonary delivery systems of large molecule drugs as rh-insulin.

  17. Innate Defense against Influenza A Virus: Activity of Human Neutrophil Defensins and Interactions of Defensins with Surfactant Protein D

    DEFF Research Database (Denmark)

    Hartshorn, Kevan L.; White, Mitchell R.; Tecle, Tesfaldet

    2006-01-01

    Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection, in part by modifying interactions with neutrophils. Human neutrophil defensins (HNPs) inhibit infectivity of enveloped viruses, including IAV. Our goal in this study was to characte......Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection, in part by modifying interactions with neutrophils. Human neutrophil defensins (HNPs) inhibit infectivity of enveloped viruses, including IAV. Our goal in this study...... with the hemagglutination-inhibiting activity of SP-D. HNPs had significant viral neutralizing activity against divergent IAV strains. However, the HNPs generally had competitive effects when combined with SP-D in assays using an SP-D-sensitive IAV strain. In contrast, cooperative antiviral effects were noted in some...

  18. Association of surfactant protein A polymorphisms with otitis media in infants at risk for asthma

    Directory of Open Access Journals (Sweden)

    Bracken Michael B

    2006-08-01

    Full Text Available Abstract Background Otitis media is one of the most common infections of early childhood. Surfactant protein A functions as part of the innate immune response, which plays an important role in preventing infections early in life. This prospective study utilized a candidate gene approach to evaluate the association between polymorphisms in loci encoding SP-A and risk of otitis media during the first year of life among a cohort of infants at risk for developing asthma. Methods Between September 1996 and December 1998, women were invited to participate if they had at least one other child with physician-diagnosed asthma. Each mother was given a standardized questionnaire within 4 months of her infant's birth. Infant respiratory symptoms were collected during quarterly telephone interviews at 6, 9 and 12 months of age. Genotyping was done on 355 infants for whom whole blood and complete otitis media data were available. Results Polymorphisms at codons 19, 62, and 133 in SP-A1, and 223 in SP-A2 were associated with race/ethnicity. In logistic regression models incorporating estimates of uncertainty in haplotype assignment, the 6A4/1A5haplotype was protective for otitis media among white infants in our study population (OR 0.23; 95% CI 0.07,0.73. Conclusion These results indicate that polymorphisms within SP-A loci may be associated with otitis media in white infants. Larger confirmatory studies in all ethnic groups are warranted.

  19. Surfactant protein A expression in human normal and neoplastic breast epithelium.

    Science.gov (United States)

    Braidotti, P; Cigala, C; Graziani, D; Del Curto, B; Dessy, E; Coggi, G; Bosari, S; Pietra, G G

    2001-11-01

    We studied the presence of surfactant protein A (Sp-A) immunoreactivity and messenger RNA in 62 normal and abnormal breast samples. Sections were immunostained with polyclonal anti-Sp-A antibody. The association between Sp-A immunoreactivity and histologic grade of 32 invasive ductal carcinomas was assessed by 3 pathologists who scored the intensity of Sp-A immunoreactivity times the percentage of tumor immunostained; individual scores were averaged, and the final scores were correlated with tumor grade, proliferative index, and expression of estrogen and progesterone receptors. Strong Sp-A immunoreactivity was present at the luminal surface of ductal epithelial cells in normal breast samples and in benign lesions; carcinomas displayed variable immunoreactivity, inversely proportional to the degree of differentiation. Sp-A messenger RNA was detected by reverse transcriptase-polymerase chain reaction in 3 of 3 normal breast samples and 9 of 9 carcinomas. The significance of Sp-A expression in breast epithelium requires further study; possibly it has a role in native host defense or epithelial differentiation.

  20. Early expression of surfactant proteins D in Fusarium solani infected rat cornea.

    Science.gov (United States)

    Che, Cheng-Ye; Li, Xiao-Jing; Jia, Wen-Yan; Li, Na; Xu, Qiang; Lin, Jing; Wang, Qing; Jiang, Nan; Hu, Li-Ting; Zhao, Gui-Qiu

    2012-01-01

    To investigate the early expression of surfactant proteins D(SP-D) in Fusarium solani infected rat cornea. Wistar rats were divided into group A, B and C randomly. The right eyes were chosen as the experiment one. Group A was control group. Group B was not inoculated with Fusarium solani. Group C was taken as fusarium solani keratitis model. Five rats in group B and C were executed randomly at 6, 12, 24, 48 and 96 hours respectively after the experimental model being established. The expression of SP-D was assessed through immunohistochemistry and reverse transcription polymerase chain reaction(RT-PCR). RT-PCR detected that the SP-D mRNA expression was low in the corneal of normal rats and group B. The expression of fungal infected cornea increased gradually and reached the peak at 24 hours in group C. The synchronous expression of group B and C were in significant difference (Pfusarium solani infected cornea. SP-D may play a role in the early innate immunity response of the corneal resistance to Fusarium solani infection.

  1. Alcohol--Induced Polyelectrolyte-Surfactant Complex Coacervate Systems: Characterization and Applications in Enzyme and Protein Extraction

    Science.gov (United States)

    Nejati Moshtaghin, Mahboubeh

    The focus of this thesis is to achieve a better understanding of the newly discovered surfactant-polyelectrolyte complex coacervate (SPCC) systems induced by fluoroalcohol/acid as well as short chain aliphatic alcohol; and to elucidate their applications in extraction and enrichment of proteins and enzyme. We have discovered that fluoroalcohols and --acids induce complex coacervation and phase separation in the aqueous mixtures of oppositely charged anionic polyelectrolytes; specifically, sodium salts of polyacrylic acid and polymethacrylic acid and cationic surfactant (cetyltrimethylammonium bromide, CTAB) over a broad range of concentrations of mole fractions of the oppositely charged amphiphiles. Accordingly, these new classes of coacervators will significantly broaden the scope and facilitate engineering of new coacervate phases. Toward these goals, we have inspected the formation of surfactant-polyelectrolyte complex coacervates in the presence of fluoroalcohols namely hexafluoroisopropanol (HFIP) and Trifluoroethanol (TFE). Furthermore, the extent of coacervation as a function of concentrations the system components, and charge ratios of the oppositely charged amphiphiles has been investigated. Polyelectrolytes are considered to be milder reagents, as compared to surfactants, regarding proteins denaturation. This highlights the importance of a detailed investigation of the efficiency of our coacervate systems for extraction and preconcentration of proteins and enzymes, especially, when the biological activity of the extracted proteins needs to be maintained based on the objectives mentioned above, the results of the investigations have been organized in four chapters. In Chapter II, the phase behavior of the FA-SPCC will be investigated. The objective is to examine the phase behavior and phase properties with respect to the extent of coacervation in different solution conditions. In particular, the effects of different solution variables such as concentration

  2. Exploring the affinity binding of alkylmaltoside surfactants to bovine serum albumin and their effect on the protein stability: A spectroscopic approach.

    Science.gov (United States)

    Hierrezuelo, J M; Carnero Ruiz, C

    2015-08-01

    Steady-state and time-resolved fluorescence together with circular dichroism (CD) spectroscopic studies was performed to examine the interactions between bovine serum albumin (BSA) and two alkylmaltoside surfactants, i.e. n-decyl-β-D-maltoside (β-C10G2) and n-dodecyl-β-D-maltoside (β-C12G2), having identical structures but different tail lengths. Changes in the intrinsic fluorescence of BSA from static as well as dynamic measurements revealed a weak protein-surfactant interaction and gave the corresponding binding curves, suggesting that the binding mechanism of surfactants to protein is essentially cooperative in nature. The behavior of both surfactants is similar, so that the differences detected were attributed to the more hydrophobic nature of β-C12G2, which favors the adsorption of micelle-like aggregates onto the protein surface. These observations were substantially demonstrated by data derived from synchronous, three-dimensional and anisotropy fluorescence experiments. Changes in the secondary structure of the protein induced by the interaction with surfactants were analyzed by CD to determine the contents of α-helix and β-strand. It was noted that whereas the addition of β-C10G2 appears to stabilize the secondary structure of the protein, β-C12G2 causes a marginal denaturation of BSA for a protein:surfactant molar ratio as high as 1 to 100.

  3. Reduced influenza viral neutralizing activity of natural human trimers of surfactant protein D

    Directory of Open Access Journals (Sweden)

    Sorensen Grith L

    2007-02-01

    Full Text Available Abstract Background Surfactant protein D (SP-D plays important roles in innate host defense against influenza A virus (IAV infection. Common human polymorphisms of SP-D have been found in many human populations and associated with increased risk of certain infections. We recently reported that the Thr/Thr 11 form of SP-D is associated with low serum levels and assembles predominantly as trimers as opposed to the more common multimeric forms of SP-D. Methods Preliminary experiments were done to establish the effects of different monoclonal antibodies against SP-D on ability of SP-D to bind to or neutralize the virus. We then purified natural human trimeric and multimeric forms of SP-D from amniotic fluid and tested ability of these preparations to bind to IAV, to inhibit infectivity and hemagglutination activity of IAV in vitro. Results In initial experiments mAbs directed against different areas on the CRD of SP-D were found to have differing effects on antiviral activity. Using an mAb that did not interfere with antiviral activity of SP-D, we confirm that natural SP-D trimers had reduced ability to bind to IAV. In addition, the trimers had reduced ability to neutralize IAV as compared to natural human SP-D multimers as well as reduced hemagglutination inhibiting activity against several strains of IAV. Natural SP-D trimers also had different interactions with human neutrophil peptide defensins (HNPs in viral neutralization assays as compared to multimeric SP-D. Conclusion These studies indicate that a common human polymorphic form of SP-D may modulate host defense against IAV and give impetus to clinical studies correlating this genotype with risk for IAV infection in susceptible groups. We also show that mAbs directed against different areas on the carbohydrate recognition domain of SP-D can be useful for dissecting out different functional properties of the protein.

  4. Influencia del reclutamiento alveolar sobre los efectos del surfactante exógeno Influence of pulmonary recruitment on exogenous surfactant effects

    Directory of Open Access Journals (Sweden)

    Néstor R. Herrera

    2006-02-01

    response to exogenous surfactant administration and the effects of baseline pulmonary volume subsequently used in 20 adult albino rats. Lung-injury was induced by repeated lavages with saline solution. Gas exchange, hemodynamic status, lung mechanics and histopathology were assessed. The rats were divided into four experimental groups. Group 1 was delivered 30 cmH2O sustained insufflation over 15 seconds prior to the surfactant. It was subsequently ventilated at positive end-expiratory pressure (PEEP of 10 cm H2O. Group 2 did not receive sustained insufflation and was ventilated at PEEP of 10 cm H2O. Group 3 was delivered sustained insufflation and was ventilated with PEEP of 4 cm H2O; and group 4 did not receive sustained insufflation and was ventilated with PEEP of 4 cm H2O. The surfactant immediate effect was not modified by previous sustained insufflation administration. Increased PaO2 associated to high functional residual capacity (FRC (Group 1 p=0.0001; Group 2 p=0.0001, regardless of sustained insufflation, was observed. The use of sustained insufflation prior to surfactant administration along with high FRC ventilation was associated with polymorphonuclear infiltrates beneath the bronchiolar epithelium (p=0.008. Our results do not advocate the use of sustained insufflation prior to the administration of exogenous surfactant.

  5. POLYMERIC SURFACTANT STRUCTURE

    Institute of Scientific and Technical Information of China (English)

    P.M. Saville; J.W. White

    2001-01-01

    Polymeric surfactants are amongst the most widespread of all polymers. In nature, proteins and polysaccharides cause self organization as a result of this surfactancy; in industry, polymeric surfactants play key roles in the food, explosives and surface coatings sectors. The generation of useful nano- and micro-structures in films and emulsions as a result of polymer amphiphilicity and the application of mechanical stress is discussed. The use of X-ray and neutron small angle scattering and reflectivity to measure these structures and their dynamic properties will be described. New results on linear and dendritic polymer surfactants are presented.

  6. Surfactant for pediatric acute lung injury.

    Science.gov (United States)

    Willson, Douglas F; Chess, Patricia R; Notter, Robert H

    2008-06-01

    This article reviews exogenous surfactant therapy and its use in mitigating acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) in infants, children, and adults. Biophysical and animal research documenting surfactant dysfunction in ALI/ARDS is described, and the scientific rationale for treatment with exogenous surfactant is discussed. Major emphasis is placed on reviewing clinical studies of surfactant therapy in pediatric and adult patients who have ALI/ARDS. Particular advantages from surfactant therapy in direct pulmonary forms of these syndromes are described. Also discussed are additional factors affecting the efficacy of exogenous surfactants in ALI/ARDS.

  7. Weak and saturable protein-surfactant interactions in the denaturation of apo-alpha-lactalbumin by acidic and lactonic sophorolipid

    Directory of Open Access Journals (Sweden)

    Kell K Andersen

    2016-11-01

    Full Text Available Biosurfactants are of growing interest as sustainable alternatives to fossil-fuel-derived chemical surfactants, particularly for the detergent industry. To realize this potential, it is necessary to understand how they affect proteins which they may encounter in their applications. However knowledge of such interactions is limited. Here we present a study of the interactions between the model protein apo-alpha-lactalbumin and the biosurfactant sophorolipid (SL produced by the yeast Starmerella bombicola. SL occurs both as an acidic and a lactonic form; the lactonic form (lactSL is sparingly soluble and has a lower critical micelle concentration than the acidic form (acidSL. We show that acidSL affects apo-aLA in a similar way to the related glycolipid biosurfactant rhamnolipid (RL, with the important difference that RL is also active below the cmc in contrast to acidSL. Using isothermal titration calorimetry data, we show that acidSL has weak and saturable interactions with apo-aLA at low concentrations; due to the relatively low cmc of acidSL (which means that the monomer concentration is limited to ca. 0-1 mM SL, it is only possible to observe interactions with monomeric acidSL at high apo-aLA concentrations. However, the denaturation kinetics of apo-aLA in the presence of acidSL are consistent with a collaboration between monomeric and micellar surfactant species, similar to RL and nonionic or zwitterionic surfactants. Inclusion of lactSL as mixed micelles with acidSL lowers the cmc and this effectively reduces the rate of unfolding, emphasizing that SL like other biosurfactants is a gentle anionic surfactant. Our data highlight the potential of these biosurfactants for future use in the detergent industry.

  8. Surfactant protein B gene polymorphism in preterm babies with respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    P.P.R. Lyra

    2011-01-01

    Full Text Available The etiology of respiratory distress syndrome (RDS is multifactorial and multigenic. Studies have suggested that polymorphisms and mutations in the surfactant protein B (SP-B gene are associated with the pathogenesis of RDS. The objectives of this study were to determine and compare the frequencies of SP-B gene polymorphisms in preterm babies with and without RDS. We studied 151 neonates: 79 preterm babies without RDS and 72 preterm newborns with RDS. The following four SP-B gene polymorphisms were analyzed: A/C at -18, C/T at 1580, A/G at 9306, and G/C at nucleotide 8714. The polymorphisms were detected by PCR amplification of genomic DNA and genotyping. The genotypes were determined using PCR-based converted restriction fragment length polymorphisms. The control group consisted of 42 (53% girls and 37 (47% boys. Weight ranged from 1170 to 3260 g and mean gestational age (GA was 33.9 weeks (range: 29 to 35 weeks and 6 days. The RDS group consisted of 31 (43% girls and 41 (57% boys. Weight ranged from 614 to 2410 g and mean GA was 32 weeks (range: 26 to 35 weeks. The logistic regression model showed that GA was the variable that most contributed to the occurrence of RDS. The AG genotype of the A/G polymorphism at position 9306 of the SP-B gene was a protective factor in this population (OR = 0.1681; 95%CI = 0.0426-0.6629. We did not detect differences in the frequencies of the other polymorphisms between the two groups of newborns.

  9. Protective Role of Surfactant Protein D in Ocular Staphylococcus aureus Infection.

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    Zhiyong Zhang

    Full Text Available Staphylococcus aureus is one of the most common pathogens causing keratitis. Surfactant protein D (SP-D plays a critical role in host defense and innate immunity. In order to investigate the role of SP-D in ocular S. aureus infection, the eyes of wild-type (WT and SP-D knockout (SP-D KO C57BL/6 mice were infected with S. aureus (10(7 CFU/eye in the presence and absence of cysteine protease inhibitor(E64.Bacterial counts in the ocular surface were examined 3, 6, 12, 24 hrs after infection. Bacterial phagocytosis by neutrophils and bacterial invasion in ocular epithelial cells were evaluated quantitatively. S. aureus-induced ocular injury was determined with corneal fluorescein staining. The results demonstrated that SP-D is expressed in ocular surface epithelium and the lacrimal gland; WT mice had increased clearance of S. aureus from the ocular surface (p<0.05 and reduced ocular injury compared with SP-D KO mice. The protective effects of SP-D include increased bacterial phagocytosis by neutrophils (p<0.05 and decreased bacterial invasion into epithelial cells (p<0.05 in WT mice compared to in SP-D KO mice. In the presence of inhibitor (E64, WT mice showed enhanced bacterial clearance (p<0.05 and reduced ocular injury compared to absent E64 while SP-D KO mice did not. Collectively, we concluded that SP-D protects the ocular surface from S. aureus infection but cysteine protease impairs SP-D function in this murine model, and that cysteine protease inhibitor may be a potential therapeutic agent in S. aureus keratitis.

  10. Lung surfactant protein D (SP-D) response and regulation during acute and chronic lung injury.

    Science.gov (United States)

    Gaunsbaek, Maria Quisgaard; Rasmussen, Karina Juhl; Beers, Michael F; Atochina-Vasserman, Elena N; Hansen, Soren

    2013-06-01

    Surfactant protein D (SP-D) is a collection that plays important roles in modulating host defense functions and maintaining phospholipid homeostasis in the lung. The aim of current study was to characterize comparatively the SP-D response in bronchoalveolar lavage (BAL) and serum in three murine models of lung injury, using a validated ELISA technology for estimation of SP-D levels. Mice were exposed to lipopolysaccharide, bleomycin, or Pneumocystis carinii (Pc) and sacrificed at different time points. In lipopolysaccharide-challenged mice, the level of SP-D in BAL increased within 6 h, peaked at 51 h (4,518 ng/ml), and returned to base level at 99 h (612 ng/ml). Serum levels of SP-D increased immediately (8.6 ng/ml), peaked at 51 h (16 ng/ml), and returned to base levels at 99 h (3.8 ng/ml). In a subacute bleomycin inflammation model, SP-D levels were 4,625 and 367 ng/ml in BAL and serum, respectively, 8 days after exposure. In a chronic Pc inflammation model, the highest level of SP-D was observed 6 weeks after inoculation, with BAL and serum levels of 1,868 and 335 ng/ml, respectively. We conclude that serum levels of SP-D increase during lung injury, with a sustained increment during chronic inflammation compared with acute inflammation. A quick upregulation of SP-D in serum in response to acute airway inflammation supports the notion that SP-D translocates from the airways into the vascular system, in favor of being synthesized systemically. The study also confirms the concept of using increased SP-D serum levels as a biomarker of especially chronic airway inflammation.

  11. A systems approach to mapping transcriptional networks controlling surfactant homeostasis

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    Dave Vrushank

    2010-07-01

    Full Text Available Abstract Background Pulmonary surfactant is required for lung function at birth and throughout life. Lung lipid and surfactant homeostasis requires regulation among multi-tiered processes, coordinating the synthesis of surfactant proteins and lipids, their assembly, trafficking, and storage in type II cells of the lung. The mechanisms regulating these interrelated processes are largely unknown. Results We integrated mRNA microarray data with array independent knowledge using Gene Ontology (GO similarity analysis, promoter motif searching, protein interaction and literature mining to elucidate genetic networks regulating lipid related biological processes in lung. A Transcription factor (TF - target gene (TG similarity matrix was generated by integrating data from different analytic methods. A scoring function was built to rank the likely TF-TG pairs. Using this strategy, we identified and verified critical components of a transcriptional network directing lipogenesis, lipid trafficking and surfactant homeostasis in the mouse lung. Conclusions Within the transcriptional network, SREBP, CEBPA, FOXA2, ETSF, GATA6 and IRF1 were identified as regulatory hubs displaying high connectivity. SREBP, FOXA2 and CEBPA together form a common core regulatory module that controls surfactant lipid homeostasis. The core module cooperates with other factors to regulate lipid metabolism and transport, cell growth and development, cell death and cell mediated immune response. Coordinated interactions of the TFs influence surfactant homeostasis and regulate lung function at birth.

  12. Surfactant therapy in late preterm infants

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    Murat Yurdakök

    2013-06-01

    Full Text Available Late preterm (LPT neonates are at a high risk for respiratory distress soon after birth due to respiratory distress syndrome (RDS, transient tachypnea of the newborn, persistent pulmonary hypertension, and pneumonia along with an increased need for surfactant replacement therapy, continuous positive airway pressure, and ventilator support when compared with the term neonates. In the past, studies on outcomes of infants with respiratory distress have primarily focused on extremely premature infants, leading to a gap in knowledge and understanding of the developmental biology and mechanism of pulmonary diseases in LPT neonates. Surfactant deficiency is the most frequent etiology of RDS in very preterm and moderately preterm infants, while cesarean section and lung infection play major roles in RDS development in LPT infants. The clinical presentation and the response to surfactant therapy in LPT infants may be different than that seen in very preterm infants. Incidence of pneumonia and occurrence of pneumothorax are significantly higher in LPT and term infants. High rates of pneumonia in these infants may result in direct injury to the type II alveolar cells of the lung with decreasing synthesis, release, and processing of surfactant. Increased permeability of the alveolar capillary membrane to both fluid and solutes is known to result in entry of plasma proteins into the alveolar hypophase, further inhibiting the surface properties of surfactant. However, the oxygenation index value do not change dramatically after ventilation or surfactant administration in LPT infants with RDS compared to very preterm infants. These finding may indicate a different pathogenesis of RDS in late preterm and term infants. In conclusion, surfactant therapy may be of significant benefit in LPT infants with serious respiratory failure secondary to a number of insults. However, optimal timing and dose of administration are not so clear in this group. Additional

  13. Surfactant protein-A suppresses eosinophil-mediated killing of Mycoplasma pneumoniae in allergic lungs.

    Directory of Open Access Journals (Sweden)

    Julie G Ledford

    Full Text Available Surfactant protein-A (SP-A has well-established functions in reducing bacterial and viral infections but its role in chronic lung diseases such as asthma is unclear. Mycoplasma pneumoniae (Mp frequently colonizes the airways of chronic asthmatics and is thought to contribute to exacerbations of asthma. Our lab has previously reported that during Mp infection of non-allergic airways, SP-A aides in maintaining airway homeostasis by inhibiting an overzealous TNF-alpha mediated response and, in allergic mice, SP-A regulates eosinophilic infiltration and inflammation of the airway. In the current study, we used an in vivo model with wild type (WT and SP-A(-/- allergic mice challenged with the model antigen ovalbumin (Ova that were concurrently infected with Mp (Ova+Mp to test the hypothesis that SP-A ameliorates Mp-induced stimulation of eosinophils. Thus, SP-A could protect allergic airways from injury due to release of eosinophil inflammatory products. SP-A deficient mice exhibit significant increases in inflammatory cells, mucus production and lung damage during concurrent allergic airway disease and infection (Ova+Mp as compared to the WT mice of the same treatment group. In contrast, SP-A deficient mice have significantly decreased Mp burden compared to WT mice. The eosinophil specific factor, eosinophil peroxidase (EPO, which has been implicated in pathogen killing and also in epithelial dysfunction due to oxidative damage of resident lung proteins, is enhanced in samples from allergic/infected SP-A(-/- mice as compared to WT mice. In vitro experiments using purified eosinophils and human SP-A suggest that SP-A limits the release of EPO from Mp-stimulated eosinophils thereby reducing their killing capacity. These findings are the first to demonstrate that although SP-A interferes with eosinophil-mediated biologic clearance of Mp by mediating the interaction of Mp with eosinophils, SP-A simultaneously benefits the airway by limiting inflammation

  14. Molecular characterization of the porcine surfactant, pulmonary-associated protein C gene

    DEFF Research Database (Denmark)

    Cirera, S.; Nygård, A.B.; Jensen, H.E.

    2006-01-01

    high levels of conservation. Northern blot studies showed lung-specific expression of the full-length SFTPC transcript, appearing in 50-day-old fetus and increasing during lung development. Both SFTPC transcripts were detected mainly in lung by real-time RT-PCR and they were significantly down...

  15. Proteomic analysis reveals down-regulation of surfactant protein B in murine type II pneumocytes infected with influenza A virus.

    Science.gov (United States)

    Kebaabetswe, Lemme P; Haick, Anoria K; Gritsenko, Marina A; Fillmore, Thomas L; Chu, Rosalie K; Purvine, Samuel O; Webb-Robertson, Bobbie-Jo; Matzke, Melissa M; Smith, Richard D; Waters, Katrina M; Metz, Thomas O; Miura, Tanya A

    2015-09-01

    Infection of type II alveolar epithelial (ATII) cells by influenza A viruses (IAV) correlates with severe respiratory disease in humans and mice. To understand pathogenic mechanisms during IAV infection of ATII cells, murine ATII cells were cultured to maintain a differentiated phenotype, infected with IAV-PR8, which causes severe lung pathology in mice, and proteomics analyses were performed using liquid chromatography-mass spectrometry. PR8 infection increased levels of proteins involved in interferon signaling, antigen presentation, and cytoskeleton regulation. Proteins involved in mitochondrial membrane permeability, energy metabolism, and chromatin formation had reduced levels in PR8-infected cells. Phenotypic markers of ATII cells in vivo were identified, confirming the differentiation status of the cultures. Surfactant protein B had decreased levels in PR8-infected cells, which was confirmed by immunoblotting and immunofluorescence assays. Analysis of ATII cell protein profiles will elucidate cellular processes in IAV pathogenesis, which may provide insight into potential therapies to modulate disease severity.

  16. Expression, stabilization and purification of membrane proteins via diverse protein synthesis systems and detergents involving cell-free associated with self-assembly peptide surfactants.

    Science.gov (United States)

    Zheng, Xuan; Dong, Shuangshuang; Zheng, Jie; Li, Duanhua; Li, Feng; Luo, Zhongli

    2014-01-01

    G-protein coupled receptors (GPCRs) are involved in regulating most of physiological actions and metabolism in the bodies, which have become most frequently addressed therapeutic targets for various disorders and diseases. Purified GPCR-based drug discoveries have become routine that approaches to structural study, novel biophysical and biochemical function analyses. However, several bottlenecks that GPCR-directed drugs need to conquer the problems including overexpression, solubilization, and purification as well as stabilization. The breakthroughs are to obtain efficient protein yield and stabilize their functional conformation which are both urgently requiring of effective protein synthesis system methods and optimal surfactants. Cell-free protein synthesis system is superior to the high yields and post-translation modifications, and early signs of self-assembly peptide detergents also emerged to superiority in purification of membrane proteins. We herein focus several predominant protein synthesis systems and surfactants involving the novel peptide detergents, and uncover the advantages of cell-free protein synthesis system with self-assembling peptide detergents in purification of functional GPCRs. This review is useful to further study in membrane proteins as well as the new drug exploration.

  17. Similarities in Self-Assembly of Proteins and Surfactants: an Attempt to Bridge the Gap

    NARCIS (Netherlands)

    Linden, van der E.; Venema, P.

    2007-01-01

    The area of surfactant self assembly has already received attention for more than half a century. Considerable progress has been made in regards to connecting the molecular properties to the assembly morphology and the phase behaviour, where a multitude of different (rather exotic) types of

  18. Weak and Saturable Protein-Surfactant Interactions in the Denaturation of Apo-α-Lactalbumin by Acidic and Lactonic Sophorolipid

    DEFF Research Database (Denmark)

    Andersen, Kell K; Vad, Brian S; Roelants, Sophie;

    2016-01-01

    Biosurfactants are of growing interest as sustainable alternatives to fossil-fuel-derived chemical surfactants, particularly for the detergent industry. To realize this potential, it is necessary to understand how they affect proteins which they may encounter in their applications. However...... the cmc in contrast to acidSL. Using isothermal titration calorimetry data, we show that acidSL has weak and saturable interactions with apo-aLA at low concentrations; due to the relatively low cmc of acidSL (which means that the monomer concentration is limited to ca. 0-1 mM SL), it is only possible...

  19. Smoking and polymorphisms of genes encoding mannose-binding lectin and surfactant protein-D in patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Kristiansen, Malthe; Frisch, Morten; Madsen, Hans Ole;

    2014-01-01

    To investigate whether polymorphisms in genes coding for mannose-binding lectin (MBL) and surfactant protein-D (SP-D) are associated directly or by interaction with smoking with rheumatoid arthritis (RA), anti-citrullinated peptide antibody (ACPA) positive RA, and erosive RA. MBL2 genotypes, SFTPD...... genotype at codon 11, and HLA-shared epitope were determined in 456 patients with rheumatoid arthritis and 533 sex- and age-matched controls. Patients were grouped according to the presence of ACPA antibodies and RA-associated bone erosions and sub-stratified according to smoking status as never or ever...

  20. An enzyme-linked immunosorbent assay (ELISA) for quantification of mouse surfactant protein D (SP-D)

    DEFF Research Database (Denmark)

    Hansen, Soren; Schmidt, Vivi; Steffensen, Maria Abildgaard;

    2008-01-01

    Surfactant protein D (SP-D) is a pattern recognition molecule of the collectin family of C-type lectins. It is found in the airways and at mucosal surfaces. SP-D is part of the innate immune system where it neutralizes and leads to elimination of microorganisms. It regulates the functions of other...... innate immune cells, such as macrophages and neutrophils. It also modulates the adaptive immune response by interacting with antigen-presenting cells and T cells. Monoclonal anti-mouse-SP-D antibodies were raised from SP-D deficient mice using recombinant SP-D as antigen. Ten monoclonal antibodies were...

  1. Deleted in Malignant Brain Tumors 1 (DMBT1 is present in hyaline membranes and modulates surface tension of surfactant

    Directory of Open Access Journals (Sweden)

    Griese Matthias

    2007-10-01

    Full Text Available Abstract Background Deleted in Malignant Brain Tumors 1 (DMBT1 is a secreted scavenger receptor cysteine-rich protein that binds various bacteria and is thought to participate in innate pulmonary host defense. We hypothesized that pulmonary DMBT1 could contribute to respiratory distress syndrome in neonates by modulating surfactant function. Methods DMBT1 expression was studied by immunohistochemistry and mRNA in situ hybridization in post-mortem lungs of preterm and full-term neonates with pulmonary hyaline membranes. The effect of human recombinant DMBT1 on the function of bovine and porcine surfactant was measured by a capillary surfactometer. DMBT1-levels in tracheal aspirates of ventilated preterm and term infants were determined by ELISA. Results Pulmonary DMBT1 was localized in hyaline membranes during respiratory distress syndrome. In vitro addition of human recombinant DMBT1 to the surfactants increased surface tension in a dose-dependent manner. The DMBT1-mediated effect was reverted by the addition of calcium depending on the surfactant preparation. Conclusion Our data showed pulmonary DMBT1 expression in hyaline membranes during respiratory distress syndrome and demonstrated that DMBT1 increases lung surface tension in vitro. This raises the possibility that DMBT1 could antagonize surfactant supplementation in respiratory distress syndrome and could represent a candidate target molecule for therapeutic intervention in neonatal lung disease.

  2. Correlations of Ventricular Enlargement with Rheologically Active Surfactant Proteins in Cerebrospinal Fluid

    Science.gov (United States)

    Schob, Stefan; Weiß, Alexander; Dieckow, Julia; Richter, Cindy; Pirlich, Mandy; Voigt, Peter; Surov, Alexey; Hoffmann, Karl-Titus; Quaeschling, Ulf; Preuß, Matthias

    2017-01-01

    Purpose: Surfactant proteins (SPs) are involved in the regulation of rheological properties of body fluids. Concentrations of SPs are altered in the cerebrospinal fluid (CSF) of hydrocephalus patients. The common hallmark of hydrocephalus is enlargement of the brain ventricles. The relationship of both phenomena has not yet been investigated. The aim of this study was to evaluate the association between SP concentrations in the CSF and enlargement of the brain ventricles. Procedures: Ninty-six individuals (41 healthy subjects and 55 hydrocephalus patients) were included in this retrospective analysis. CSF specimens were analyzed for SP-A, SP-B, SP-C and SP-D concentrations by use of enzyme linked immunosorbent assays (ELISA). Ventricular enlargement was quantified in T2 weighted (T2w) magnetic resonance imaging (MRI) sections using an uni-dimensional (Evans’ Index) and a two-dimensional approach (lateral ventricles area index, LVAI). Results: CSF-SP concentrations (mean ± standard deviation in ng/ml) were as follows: SP-A 0.71 ± 0.58, SP-B 0.18 ± 0.43, SP-C 0.89 ± 0.77 and SP-D 7.4 ± 5.4. Calculated values of Evans’ Index were 0.37 ± 0.11, a calculation of LVAI resulted in 0.18 ± 0.15 (each mean ± standard deviation). Significant correlations were identified for Evans’ Index with SP-A (r = 0.388, p < 0.001) and SP-C (r = 0.392, p < 0.001), LVAI with SP-A (r = 0.352, p = 0.001), SP-C (r = 0.471, p < 0.001) and SP-D (r = 0.233, p = 0.025). Furthermore, SP-C showed a clear inverse correlation with age (r = −0.357, p = 0.011). Conclusion: The present study confirmed significant correlations between SPs A, C and D in the CSF with enlargement of the inner CSF spaces. In conclusion, SPs clearly play an important role for CSF rheology. CSF rheology is profoundly altered in hydrocephalic diseases, however, diagnosis and therapy of hydrocephalic conditions are still almost exclusively based on ventricular enlargement. Until now it was unclear, whether the

  3. Interactions of surfactants with a water treatment protein from Moringa oleifera seeds in solution studied by zeta-potential and light scattering measurements.

    Science.gov (United States)

    Kwaambwa, Habauka M; Rennie, Adrian R

    2012-04-01

    Protein extracted from Moringa oleifera (MO) seeds has been advocated as a cheap and environmental friendly alternative to ionic flocculants for water purification. However, the nature and mechanism of its interaction with particles in water, as well as with dissolved surface-active molecules, are not well understood. In this article, we report studies of the protein and its interaction with four surfactants using dynamic light scattering (DLS), zeta-potential and turbidity measurements. Zeta-potential measurements identified points of charge reversal and the turbidity and DLS measurements were used to characterize the microstructure and size of protein-surfactant complexes. From the points of charge reversal, it was estimated that 7 anions are required to neutralize the positive charges of each protein molecule at pH 7. For protein mixtures with sodium dodecyl sulfate and dodecyl di-acid sodium salt, the peak in turbidity corresponds to concentrations with a large change in zeta-potential. No turbidity was observed for protein mixtures with either the nonionic surfactant Triton X-100 or the zwitterionic surfactant N-dodecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate. Changes of pH in the range 4-10 have little effect on the zeta-potential, turbidity, and the hydrodynamic radius reflecting the high isoelectric point of the protein. Addition of small amounts of salt has little effect on the size of protein in solution. These results are discussed in the context of the use of the MO protein in water treatment.

  4. Lung surfactant metabolism: early in life, early in disease and target in cell therapy.

    Science.gov (United States)

    Lopez-Rodriguez, Elena; Gay-Jordi, Gemma; Mucci, Adele; Lachmann, Nico; Serrano-Mollar, Anna

    2017-03-01

    Lung surfactant is a complex mixture of lipids and proteins lining the alveolar epithelium. At the air-liquid interface, surfactant lowers surface tension, avoiding alveolar collapse and reducing the work of breathing. The essential role of lung surfactant in breathing and therefore in life, is highlighted by surfactant deficiency in premature neonates, which causes neonatal respiratory distress syndrome and results in early death after birth. In addition, defects in surfactant metabolism alter lung homeostasis and lead to disease. Special attention should be paid to two important key cells responsible for surfactant metabolism: alveolar epithelial type II cells (AE2C) and alveolar macrophages (AM). On the one hand, surfactant deficiency coming from abnormal AE2C function results in high surface tension, promoting alveolar collapse and mechanical stress in the epithelium. This epithelial injury contributes to tissue remodeling and lung fibrosis. On the other hand, impaired surfactant catabolism by AM leads to accumulation of surfactant in air spaces and the associated altered lung function in pulmonary alveolar proteinosis (PAP). We review here two recent cell therapies that aim to recover the activity of AE2C or AM, respectively, therefore targeting the restoring of surfactant metabolism and lung homeostasis. Applied therapies successfully show either transplantation of healthy AE2C in fibrotic lungs, to replace injured AE2C cells and surfactant, or transplantation of bone marrow-derived macrophages to counteract accumulation of surfactant lipid and proteinaceous material in the alveolar spaces leading to PAP. These therapies introduce an alternative treatment with great potential for patients suffering from lung diseases.

  5. Effect of pulmonary surfactant joint n-CPAP on respiratory distress syndrome in premature infants%珂立苏联合CPAP治疗早产儿呼吸窘迫综合征

    Institute of Scientific and Technical Information of China (English)

    刘健华

    2012-01-01

    目的 观察外源性肺表面活性物质联合n-CPAP治疗早产儿呼吸窘迫综合征的疗效.方法 32例患儿应用珂立苏及n-CPAP治疗,观察治疗后临床反应、血气变化、CPAP参数变化及疗效.结果 应用珂立苏及n-CPAP后患儿呼吸困难、呻吟、发绀、吸凹征明显减轻或消失,CPAP参数均下调,用药前后pH、PaO2、PaCO2差异有统计学意义(P<0.05);无气胸、肺出血等并发症,32例均治愈出院.结论 外源性肺表面活性物质珂立苏联合n-CPAP治疗早产儿呼吸窘迫综合征的疗效确切,可明显改善临床症状、血气指标及氧合状况.%Objective To observe the effects of pulmonary surfactant - Calf joint n - CPAP on respiratory distress syndrome of premature infants. Methods Thirty - two cases of premature infants with respiratory distress syndrome undergone the treatment with pulmonary surfactant - Calf joint n - CPAP. Then the clinical response, changes of blood gas index and CPAP parameter, and therapeutic effects were observed. Results After the treatment of pulmonary surfactant - Calf joint n - CPAP, the symptoms like dyspnea, retarded expiration, breath depressions sign and cyanosis were lessened and disappeared. The parameters of the CPAP were slowed down. The difference was significant when pH, PaO2 , PaCO2 were compared with those of pre - medication ( P <0. 05 ). There were no complications like pneumothorax and pulmonary hemorrhage, and all 32 cases were cured. Conclusion It is effective to use pulmonary surfactant - Calf joint n - CPAP in the treatment of respiratory distress syndrome of premature infants, which can effectively improve the clinical symptom, blood gas index and status of oxygen.

  6. RAGE-mediated extracellular matrix proteins accumulation exacerbates HySu-induced pulmonary hypertension.

    Science.gov (United States)

    Jia, Daile; He, Yuhu; Zhu, Qian; Liu, Huan; Zuo, Caojian; Chen, Guilin; Yu, Ying; Lu, Ankang

    2017-05-01

    Extracellular matrix (ECM) proteins accumulation contributes to the progression of pulmonary arterial hypertension (PAH), a rare and fatal cardiovascular condition defined by high pulmonary arterial pressure, whether primary, idiopathic, or secondary to other causes. The receptor for advanced glycation end products (RAGE) is constitutively expressed in the lungs and plays an important role in ECM deposition. Nonetheless, the mechanisms by which RAGE mediates ECM deposition/formation in pulmonary arteries and its roles in PAH progression remain unclear. Expression of RAGE and its activating ligands, S100/calgranulins and high mobility group box 1 (HMGB1), were increased in both human and mouse pulmonary arterial smooth muscle cells (PASMCs) under hypoxic conditions and were also strikingly upregulated in pulmonary arteries in hypoxia plus SU5416 (HySu)-induced PAH in mice. RAGE deletion alleviated pulmonary arterial pressure and restrained extracellular matrix accumulation in pulmonary arteries in HySu-induced PAH murine model. Moreover, blocking RAGE activity with a neutralizing antibody in human PASMCs, or RAGE deficiency in mouse PASMCs exposed to hypoxia, suppressed the expression of fibrotic proteins by reducing TGF-β1 expression. RAGE reconstitution in deficient mouse PASMCs restored hypoxia-stimulated TGF-β1 production via ERK1/2 and p38 MAPK pathway activation and subsequently increased ECM protein expression. Interestingly, HMGB1 acting on RAGE, not toll-like receptor 4 (TLR4), induced ECM deposition in PASMCs. Finally, in both idiopathic PAH patients and HySu-induced PAH mice, soluble RAGE (sRAGE) levels in serum were significantly elevated compared to those in controls. Activation of RAGE facilitates the development of hypoxia-induced pulmonary hypertension by increase of ECM deposition in pulmonary arteries. Our results indicate that sRAGE may be a potential biomarker for PAH diagnosis and disease severity, and that RAGE may be a promising target for

  7. Surfactant Protein D Levels in Umbilical Cord Blood and Capillary Blood of Premature Infants

    DEFF Research Database (Denmark)

    Dahl, Marianne; Holmskov, Uffe; Husby, Steffen

    2006-01-01

    of SP-D in capillary blood day 1 was 1,466 ng/mL (range 410-5,051 ng/mL), with lowest values in infants born with ROM and delivered vaginally. High SP-D levels in umbilical cord blood and capillary blood on day 1 were found to be more likely in infants in need for respiratory support or surfactant...

  8. Alterations in nanoparticle protein corona by biological surfactants: impact of bile salts on β-lactoglobulin-coated gold nanoparticles.

    Science.gov (United States)

    Winuprasith, Thunnalin; Chantarak, Sirinya; Suphantharika, Manop; He, Lili; McClements, David Julian

    2014-07-15

    The impact of biological surfactants (bile salts) on the protein (β-lactoglobulin) corona surrounding gold nanoparticles (200 nm) was studied using a variety of analytical techniques at pH 7: dynamic light scattering (DLS); particle electrophoresis (ζ-potential); UV-visible (UV) spectroscopy; transmission electron microscopy (TEM); and surface-enhanced Raman scattering (SERS). The bile salts adsorbed to the protein-coated nanoparticle surfaces and altered their interfacial composition, charge, and structure. SERS spectra of protein-coated nanoparticles after bile salt addition contained bands from both protein and bile salts, indicating that the protein was not fully displaced by the bile salts. UV, DLS and TEM techniques also indicated that the protein coating was not fully displaced from the nanoparticle surfaces. The impact of bile salts could be described by an orogenic mechanism: mixed interfaces were formed that consisted of islands of aggregated proteins surrounded by a sea of bile salts. This knowledge is useful for understanding the interactions of bile salts with protein-coated colloidal particles, which may be important for controlling the fate of colloidal delivery systems in the human gastrointestinal tract, or the gastrointestinal fate of ingested inorganic nanoparticles.

  9. The role of surfactant treatment in preterm infants and term newborns with acute respiratory distress syndrome.

    Science.gov (United States)

    Wirbelauer, J; Speer, C P

    2009-05-01

    Surfactant treatment in preterm infants and term newborns with (acute respiratory distress syndrome) ARDS-like severe respiratory failure has become part of an individualized treatment strategy in many intensive care units around the world. These babies constitute heterogeneous groups of gestational ages, lung maturity, as well as of the underlying disease processes and postnatal interventions. The pathophysiology of respiratory failure in preterm infants is characterized by a combination of primary surfactant deficiency and surfactant inactivation as a result of plasma proteins leaking into the airways from areas of epithelial disruption and injury. Various pre- and postnatal factors, such as exposure to chorioamnionitis, pneumonia, sepsis and asphyxia, induce an injurious inflammatory response in the lungs of preterm infants, which may subsequently affect surfactant function, synthesis and alveolar stability. Surfactant inactivation--and dysfunction--is also a hallmark in newborns with meconium aspiration syndrome (MAS), pneumonia and other disorders affecting the pulmonary function. Although for the majority of suggested indications no data from randomized controlled trials exist, a surfactant replacement that counterbalances surfactant inactivation seems to improve oxygenation and lung function in many babies with ARDS without any apparent negative side effects. Newborns with MAS will definitely benefit from a reduced need for extracorporeal membrane oxygenation (ECMO). Clinical experience seems to justify surfactant treatment in neonates with ARDS.

  10. N-trimethyl chitosan (TMC) carriers for nasal and pulmonary delivery of therapeutic proteins and vaccines

    NARCIS (Netherlands)

    Amidi, M.

    2007-01-01

    The research described in this thesis was aimed at evaluating the potential of particulate TMC carrier systems for delivering therapeutic proteins and antigens across respiratory (nasal and pulmonary) epithelia. To this end, TMC nanoparticles and microparticles loaded with different model proteins a

  11. Lung preservation in experimental ischemia/reperfusion injury and lung transplantation: a comparison of natural and synthetic surfactants.

    Science.gov (United States)

    Knudsen, Lars; Boxler, Laura; Mühlfeld, Christian; Schaefer, Inga-Marie; Becker, Laura; Bussinger, Christine; von Stietencron, Immanuel; Madershahian, Navid; Richter, Joachim; Wahlers, Thorsten; Wittwer, Thorsten; Ochs, Matthias

    2012-01-01

    Surfactant inactivation results from ischemia/reperfusion injury and plays a major role in the pathogenesis of primary graft dysfunction after clinical lung transplantation. Thus, prophylactic administration of exogenous surfactant preparations before the onset of ischemia/reperfusion has proven to be effective in preserving pulmonary structure and function. Various natural and synthetic surfactant preparations exhibit differences regarding the biochemical composition and biophysical properties. In this study we compared the efficacy of preservation of pulmonary structure and function of the natural surfactant preparations Curosurf and Survanta to that of a synthetic surfactant containing an analog of surfactant protein C (SPC-33) in a rat model of ischemia/reperfusion injury. The oxygenation capacity and peak inspiratory pressure during the reperfusion period were recorded. By applying design-based stereology at the light- and electron-microscopic level, pathologic alterations, including alveolar edema, injury of the blood-air barrier and the intra-alveolar as well as intracellular surfactant pools, were quantified. The best oxygenation and preservation of lung structure was achieved with Curosurf. Survanta treatment was associated with the most severe injury of the blood-air barrier, and SPC-33 demonstrated signs of microatelectasis. The intra-alveolar surfactant pool after Curosurf and SPC-33 was dominated by active surfactant subtypes, whereas Survanta was associated with the highest fraction of inactive surfactant. The intracellular surfactant pool did not show any differences between the treatment groups. Taken together, Curosurf achieved the best structural and functional lung preservation, whereas Survanta was inferior to both Curosurf and SPC-33. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  12. Monoclonal antibody-assisted structure-function analysis of the carbohydrate recognition domain of surfactant protein D

    DEFF Research Database (Denmark)

    Hartshorn, Kevan L; White, Mitchell R; Rynkiewicz, Michael

    2010-01-01

    Surfactant protein D (SP-D) plays important roles in host defense against a variety of pathogens including influenza A virus (IAV). Ligand binding by SP-D is mediated by the trimeric neck and carbohydrate recognition domain (NCRD). We used monoclonal antibodies (mAbs) against human SP-D and a panel...... of mutant collectin NCRD constructs to identify functionally and structurally important epitopes. The ability of SP-D to bind to IAV and mannan involved partially overlapping binding sites that are distinct from those involved in binding to the glycoprotein-340 (gp-340) scavenger receptor protein. A species...... abrogated antiviral activity, were associated with decreased binding to multiple blocking mAbs, consistent with critical structural roles. More conservative substitutions at 335, which showed a significant increase in neutralization activity, caused selective loss of binding to one mAb. The analysis reveals...

  13. Persurf, a new method to improve surfactant delivery: a study in surfactant depleted rats.

    Directory of Open Access Journals (Sweden)

    Wolfram Burkhardt

    Full Text Available PURPOSE: Exogenous surfactant is not very effective in adults with ARDS, since surfactant does not reach atelectatic alveoli. Perfluorocarbons (PFC can recruit atelectatic areas but do not replace impaired endogenous surfactant. A surfactant-PFC-mixture could combine benefits of both therapies. The aim of the proof-of-principal-study was to produce a PFC-in-surfactant emulsion (Persurf and to test in surfactant depleted Wistar rats whether Persurf achieves I. a more homogenous pulmonary distribution and II. a more homogenous recruitment of alveoli when compared with surfactant or PFC alone. METHODS: Three different PFC were mixed with surfactant and phospholipid concentration in the emulsion was measured. After surfactant depletion, animals either received 30 ml/kg of PF5080, 100 mg/kg of stained (green dye Curosurf™ or 30 ml/kg of Persurf. Lungs were fixated after 1 hour of ventilation and alveolar aeration and surfactant distribution was estimated by a stereological approach. RESULTS: Persurf contained 3 mg/ml phospholipids and was stable for more than 48 hours. Persurf-administration improved oxygenation. Histological evaluation revealed a more homogenous surfactant distribution and alveolar inflation when compared with surfactant treated animals. CONCLUSIONS: In surfactant depleted rats administration of PFC-in-surfactant emulsion leads to a more homogenous distribution and aeration of the lung than surfactant alone.

  14. 肺泡表面活性物质对肺挫伤后肺泡巨噬细胞功能的影响%Effects of pulmonary surfactant on alveolar macrophage function after pulmonary contusion

    Institute of Scientific and Technical Information of China (English)

    刘军强; 卢建; 潘铁文; 徐志飞

    2012-01-01

    Objective To observe the effects of porcine pulmonary surfactant(PPS) on the function of pulmonary alveolar macrophagesC AMs) in vitro, so as to explore the mechanism by which PPS treating pulmonary contusion in rats. Methods AMs were separated by adherent culture from bronchoalveolar lavage fluid of rats with pulmonary contusion. The AMs were then cultured with media containing PPS (100 jig/ml or 200 fig/ml) , LPS (20 jug/ml) +PPS (100 jug/ml or 200 Fg/ ml), or LPS (20 /jg/ml) alone for 2 h. Then the phagocytic function of AMs in each group was examined with fungus. TNF-a mRNA was determined by RT-PCR in AMs of each group. AMs untreated with PPS and LPS were taken as blank control. Results The phagocytic function of the AMs and the expression of TNF-a mRNA were not significantly affected by PPS alone compared with the control group. LPS stimulation increased the phagocytic function of AMs and the TNF-a mRNA expression in AMs. PPS showed no significant effect on LPS-induced increase of phagocytic function of AMs, but it could greatly inhibit LPS-induced TNF-a mRNA increase. Conclusion PPS has no noticeable effect on the phagocytic function of the AMs, but it can inhibit TNF-a mRNA expression induced by LPS in AMs.%目的 观察研究外源性猪肺表面活性物质(PPS)对肺挫伤大鼠肺泡巨噬细胞(AM)的吞噬功能和分泌功能的影响,探讨补充PPS对肺挫伤大鼠的治疗作用及其机制.方法 采用贴壁培养的方法,分离肺挫伤大鼠肺泡灌洗液中的AM,将分离的AM于普通培养液、含PPS(100μg/ml或200 μg/ml)的培养液、含LPS(20 μg/ml)的培养液或含LPS(20 μg/ml)+PPS(100 μg/ml或200 μg/ml)的培养液中培养2h后,采用真菌吞噬法测定各组细胞的吞噬功能;采用RTPCR方法测定各组细胞中TNF-α mRNA含量.结果 与对照相比,PPS单独作用对AM的吞噬功能和TNF-α mRNA含量无明显影响.经LPS刺激后AM的吞噬功能增强,TNF-α mRNA含量明显增高.PPS对LPS导致的吞噬

  15. Can Serum Surfactant Protein D or CC-Chemokine Ligand 18 Predict Outcome of Interstitial Lung Disease in Patients with Early Systemic Sclerosis?

    Science.gov (United States)

    Elhaj, Mona; Charles, Julio; Pedroza, Claudia; Liu, Xiaochun; Zhou, Xiaodong; Estrada-Y-Martin, Rosa M.; Gonzalez, Emilio B.; Lewis, Dorothy E.; Draeger, Hilda T.; Kim, Sarah; Arnett, Frank C.; Mayes, Maureen D.; Assassi, Shervin

    2013-01-01

    Objective To examine the predictive significance of 2 pneumoproteins, surfactant protein D (SP-D) and CC-chemokine ligand 18 (CCL18), for the course of systemic sclerosis (SSc)-related interstitial lung disease. Methods The pneumoproteins were determined in the baseline plasma samples of 266 patients with early SSc enrolled in the GENISOS observational cohort. They also were measured in 83 followup patient samples. Pulmonary function tests were obtained annually. The primary outcome was decline in forced vital capacity (FVC percentage predicted) over time. The predictive significance for longterm change in FVC was investigated by a joint analysis of longitudinal measurements (sequentially obtained FVC percentage predicted) and survival data. Results SP-D and CCL18 levels were both higher in patients with SSc than in matched controls (p < 0.001 and p = 0.015, respectively). Baseline SP-D levels correlated with lower concomitantly obtained FVC (r = −0.27, p < 0.001), but did not predict the short-term decline in FVC at 1 year followup visit or its longterm decline rate. CCL18 showed a significant correlation with steeper short-term decline in FVC (p = 0.049), but was not a predictor of its longterm decline rate. Similarly, a composite score of SP-D and CCL18 was a significant predictor of short-term decline in FVC but did not predict its longterm decline rate. Further, the longitudinal change in these 2 pneumoproteins did not correlate with the concomitant percentage change in FVC. Conclusion SP-D correlated with concomitantly obtained FVC, while CCL18 was a predictor of short-term decline in FVC. However, neither SP-D nor CCL18 was a longterm predictor of FVC course in patients with early SSc. PMID:23588945

  16. Surfactant protein D inhibits adherence of uropathogenic Escherichia coli to the bladder epithelial cells and the bacterium-induced cytotoxicity: a possible function in urinary tract.

    Science.gov (United States)

    Kurimura, Yuichiro; Nishitani, Chiaki; Ariki, Shigeru; Saito, Atsushi; Hasegawa, Yoshihiro; Takahashi, Motoko; Hashimoto, Jiro; Takahashi, Satoshi; Tsukamoto, Taiji; Kuroki, Yoshio

    2012-11-16

    The adherence of uropathogenic Escherichia coli (UPEC) to the host urothelial surface is the first step for establishing UPEC infection. Uroplakin Ia (UPIa), a glycoprotein expressed on bladder urothelium, serves as a receptor for FimH, a lectin located at bacterial pili, and their interaction initiates UPEC infection. Surfactant protein D (SP-D) is known to be expressed on mucosal surfaces in various tissues besides the lung. However, the functions of SP-D in the non-pulmonary tissues are poorly understood. The purposes of this study were to investigate the possible function of SP-D expressed in the bladder urothelium and the mechanisms by which SP-D functions. SP-D was expressed in human bladder mucosa, and its mRNA was increased in the bladder of the UPEC infection model in mice. SP-D directly bound to UPEC and strongly agglutinated them in a Ca(2+)-dependent manner. Co-incubation of SP-D with UPEC decreased the bacterial adherence to 5637 cells, the human bladder cell line, and the UPEC-induced cytotoxicity. In addition, preincubation of SP-D with 5637 cells resulted in the decreased adherence of UPEC to the cells and in a reduced number of cells injured by UPEC. SP-D directly bound to UPIa and competed with FimH for UPIa binding. Consistent with the in vitro data, the exogenous administration of SP-D inhibited UPEC adherence to the bladder and dampened UPEC-induced inflammation in mice. These results support the conclusion that SP-D can protect the bladder urothelium against UPEC infection and suggest a possible function of SP-D in urinary tract.

  17. Effects of the conjugation of whey proteins with gellan polysaccharides on surfactant-induced competitive displacement from the air-water interface.

    Science.gov (United States)

    Cai, B; Ikeda, S

    2016-08-01

    Whey proteins can be used to stabilize foams and emulsions against coalescence because of their ability to form viscoelastic films at the interface that resist film rupture on collision between colloidal particles. However, whey proteins are competitively displaced from the interface if small-molecule surfactants are added, leading to destabilization of the entire system. This is because surfactants are more effective in molecular packing at the interface, and they lower interfacial tension to a greater degree than whey proteins do, but their interfacial films are poor in viscoelasticity. We hypothesized that whey proteins would become more resistant to surfactant-induced competitive displacement if they were conjugated with network-forming polysaccharides. The protein moiety of the conjugate would be expected to enable its adsorption to the interface, and the polysaccharide moiety would be expected to form self-assembled networks, strengthening the interfacial film as a whole. In this study, whey proteins were conjugated with gellan polysaccharides using the Maillard reaction. Atomic force microscopy images of interfacial films formed by the whey protein-gellan conjugate at the air-water interface and transferred onto mica sheets using the Langmuir-Blodgett method revealed that gellan did form self-assembled networks at the interface and that interfacial films also contained a large number of unconjugated whey protein molecules. Following the addition of a small-molecule surfactant (Tween 20) to the sub-phase, surface pressure increased, indicating spontaneous adsorption of surfactants to the interface. Atomic force microscopy images showed decreases in interfacial area coverage by whey proteins as surface pressure increased. At a given surface pressure, the interfacial area coverage by whey protein-gellan conjugates was greater than coverage by unconjugated whey proteins, confirming that whey proteins became more resistant to surfactant-induced displacement after

  18. Dipalmitoylphosphatidylcholine is not the major surfactant phospholipid species in all mammals.

    Science.gov (United States)

    Lang, Carol J; Postle, Anthony D; Orgeig, Sandra; Possmayer, Fred; Bernhard, Wolfgang; Panda, Amiya K; Jürgens, Klaus D; Milsom, William K; Nag, Kaushik; Daniels, Christopher B

    2005-11-01

    Pulmonary surfactant, a complex mixture of lipids and proteins, lowers the surface tension in terminal air spaces and is crucial for lung function. Within an animal species, surfactant composition can be influenced by development, disease, respiratory rate, and/or body temperature. Here, we analyzed the composition of surfactant in three heterothermic mammals (dunnart, bat, squirrel), displaying different torpor patterns, to determine: 1) whether increases in surfactant cholesterol (Chol) and phospholipid (PL) saturation occur during long-term torpor in squirrels, as in bats and dunnarts; 2) whether surfactant proteins change during torpor; and 3) whether PL molecular species (molsp) composition is altered. In addition, we analyzed the molsp composition of a further nine mammals (including placental/marsupial and hetero-/homeothermic contrasts) to determine whether phylogeny or thermal behavior determines molsp composition in mammals. We discovered that like bats and dunnarts, surfactant Chol increases during torpor in squirrels. However, changes in PL saturation during torpor may not be universal. Torpor was accompanied by a decrease in surfactant protein A in dunnarts and squirrels, but not in bats, whereas surfactant protein B did not change in any species. Phosphatidylcholine (PC)16:0/16:0 is highly variable between mammals and is not the major PL in the wombat, dunnart, shrew, or Tasmanian devil. An inverse relationship exists between PC16:0/16:0 and two of the major fluidizing components, PC16:0/16:1 and PC16:0/14:0. The PL molsp profile of an animal species is not determined by phylogeny or thermal behavior. We conclude that there is no single PL molsp composition that functions optimally in all mammals; rather, surfactant from each animal is unique and tailored to the biology of that animal.

  19. The Alteration and Significance of Surfactant Protein A in Rats Chronically Exposed to Cigarette Smoke

    Institute of Scientific and Technical Information of China (English)

    Qiongjie HU; Huilan ZHANG; Shengdao XIONG; Xuemei SHI; Yongjian XU; Zhenxiang ZHANG; Guohua ZHEN; Jianping ZHAO

    2008-01-01

    In order to confirm the alteration and significance of cigarette smoke exposure on SP-A in rats, 20 Wistar rats were assigned randomly to two groups: an N group (n=10), and an S group (n=10). The ultra-structural change was observed by electron microscopy. The number of cells positive for SPA was by immunohistochemically measured. The mRNA expression in the lung tissues was deter-mined by reverse transcription polymerase chain reaction (RT-PCR). The number of cells positive for SPA of the S group (0.52±0.05) was lower than that of the N group (0.72±0.06) (P<0.05). The lev-els of mRNA of SPA in the lung tissues of the S group (0.3522±0.0512) was significantly lower than that of the N group (0.4432±0.05628) (P<0.05). It is concluded that cigarette smoke alone decreased the level of SP-A and that might have an important effect on surfactant metabolism and the host deense functions of surfactant in the peripheral airways, which might play a crucial role in the devel-opment of chronic obstructive lung disease.

  20. Effect of exogenous pulmonary surfactants on mortality rate in neonatal respiratory distress syndrome: A network meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Zhang, Liang; Cao, Hong-Yi; Zhao, Shuang; Yuan, Li-Jie; Han, Dan; Jiang, Hong; Wu, Song; Wu, Hong-Min

    2015-10-01

    The utilization of multiple natural and synthetic products in surfactant replacement therapies in treatment of neonatal respiratory distress syndrome (NRDS) prompted us to take a closer looks at these various therapeutic options and their efficacies. The purpose of our study was to evaluate the effects of six exogenous pulmonary surfactants (EPS) (Survanta, Alveofact, Infasurf, Curosurf, Surfaxin and Exosurf) on mortality rate in NRDS by a network meta-analysis. An exhaustive search of electronic databases was performed in PubMed, Ovid, EBSCO, Springerlink, Wiley, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang and VIP databases (last updated search in October 2014) to retrieve randomized controlled trials (RCTs) relevant to our study topic. Published clinical trials were screened based on the following inclusion criteria: (1) study design: RCTs; (2) interventions: treatment with Survanta, Alveofact, Infasurf, Curosurf, Surfaxin or Exosurf for NRDS; (3) study subject: infants with NRDS confirmed by clinical diagnosis; (4) outcome: the mortality rate of infants with NRDS. Statistical analysis was performed using Stata 12.0 software (Stata Corporation, College Station, TX, USA) and Comprehensive Meta-analysis (CMA 2.0) software. From the 1840 studies initially retrieved through database searches, a total of 17 high quality RCTs were selected for this network meta-analysis. The selected studies included a combined total of 57,223 infants with NRDS treated with various EPS (Survanta, 27,017; Alveofact, 159; Infasurf, 20,377; Curosurf, 20,911; Surfaxin, 646; Exosurf, 1640). Network meta-analysis results showed that the mortality rates in NRDS infants treated with Alveofact, Infasurf, Curosurf, Surfaxin, Exosurf were not significantly different compared to Survanta (Alveofact: OR = 1.163, 95% CI = 0.645-2.099, P = 0.616; Infasurf: OR = 0.985, 95% CI = 0.777-1.248, P = 0.897; Curosurf: OR = 0.789, 95% CI = 0.619-1.007, P = 0

  1. Synthetic lung surfactants containing SP-B and SP-C peptides plus novel phospholipase-resistant lipids or glycerophospholipids

    Science.gov (United States)

    Notter, Robert H.; Gupta, Rohun; Schwan, Adrian L.; Wang, Zhengdong; Shkoor, Mohanad Gh

    2016-01-01

    Background This study examines the biophysical and preclinical pulmonary activity of synthetic lung surfactants containing novel phospholipase-resistant phosphonolipids or synthetic glycerophospholipids combined with Super Mini-B (S-MB) DATK and/or SP-Css ion-lock 1 peptides that replicate the functional biophysics of surfactant proteins (SP)-B and SP-C. Phospholipase-resistant phosphonolipids used in synthetic surfactants are DEPN-8 and PG-1, molecular analogs of dipalmitoyl phosphatidylcholine (DPPC) and palmitoyl-oleoyl phosphatidylglycerol (POPG), while glycerophospholipids used are active lipid components of native surfactant (DPPC:POPC:POPG 5:3:2 by weight). The objective of the work is to test whether these novel lipid/peptide synthetic surfactants have favorable preclinical activity (biophysical, pulmonary) for therapeutic use in reversing surfactant deficiency or dysfunction in lung disease or injury. Methods Surface activity of synthetic lipid/peptide surfactants was assessed in vitro at 37 °C by measuring adsorption in a stirred subphase apparatus and dynamic surface tension lowering in pulsating and captive bubble surfactometers. Shear viscosity was measured as a function of shear rate on a Wells-Brookfield micro-viscometer. In vivo pulmonary activity was determined by measuring lung function (arterial oxygenation, dynamic lung compliance) in ventilated rats and rabbits with surfactant deficiency/dysfunction induced by saline lavage to lower arterial PO2 to C. However, dual-peptide surfactants containing 1.5% S-MB DATK + 1.5% SP-Css ion-lock 1 combined with 9:1 DEPN-8:PG-1 or 5:3:2 DPPC:POPC:POPG had the greatest in vivo activity in improving arterial oxygenation and dynamic lung compliance in ventilated animals with ARDS. Saline dispersions of these dual-peptide synthetic surfactants were also found to have shear viscosities comparable to or below those of current animal-derived surfactant drugs, supporting their potential ease of deliverability by

  2. Circadian rhythm and the influence of physical activity on circulating surfactant protein D in early and long-standing rheumatoid arthritis

    DEFF Research Database (Denmark)

    Christensen, A F; Hoegh, S V; Lottenburger, T

    2011-01-01

    Surfactant protein D (SP-D) belongs to the collectin family and has pro-and anti-inflammatory capacities depending on its oligomerization. Previously, circulating SP-D was shown to be decreased in early rheumatoid arthritis (RA) and negatively correlated to disease activity. This study aimed...

  3. Synthesis of β-arabinofuranoside glycolipids, studies of their binding to surfactant protein-A and effect on sliding motilities of M. smegmatis

    DEFF Research Database (Denmark)

    Naresh, Kottari; Avaji, Prakash Gouda; Maiti, Krishnagopal

    2012-01-01

    Surfactant protein A (SP-A), which is a lung innate immune system component, is known to bind glycolipids present at the cell surface of a mycobacterial pathogen. Lipoarabinomannan (LAM), a component of mycobacterial thick, waxy cell wall, is one of the glycolipid ligands for SP-A. In order to as...

  4. Chemotherapy modulates intestinal immune gene expression including surfactant Protein-D and deleted in malignant brain tumors 1 in piglets

    DEFF Research Database (Denmark)

    Rathe, Mathias; Thomassen, Mads; Shen, René L.

    2016-01-01

    Background: Information about chemotherapy-induced intestinal gene expression may provide insight into the mechanisms underlying gut toxicity and help identify biomarkers and targets for intervention. Methods: We analyzed jejunal tissue from piglets subjected to two different, clinically relevant...... the upregulated genes for both treatments. Conclusion: In the developing intestine, chemotherapy increases the expression of genes related to innate immune functions involved in surveillance, protection, and homeostasis of mucosal surfaces....... the BUCY and DOX piglets. Selected genes of potential biological significance with a similar change in expression across the treatments were controlled by real-time polymerase chain reaction. Key innate defense molecules, including surfactant protein-D and deleted in malignant brain tumors 1, were among...

  5. Possible influence of surfactants and proteins on the efficiency of contact agar microbiological surface sampling.

    Science.gov (United States)

    Deckers, Sylvie M; Sindic, Marianne; Anceau, Christine; Brostaux, Yves; Detry, Jean G

    2010-11-01

    Agar contact microbiological sampling techniques, based on a transfer of the microorganisms present on a surface to a culture medium, are widely used to assess and control surface cleanliness and to evaluate microbial contamination levels. The effectiveness of these techniques depends on many environmental parameters that influence the strength of attachment of the bacteria to the surface. In the present study, stainless steel and high density polyethylene surfaces were inoculated with known concentrations of Staphylococcus epidermidis. Following an experimental design, the surfaces were sampled with different types of replicate organism direct agar contact plates and Petrifilm; results indicated that recovery rates were influenced by the presence of egg white albumin or Tween 80 in the inoculum solutions or by the introduction of surfactants into the contact agar of the microbiological sampling techniques. The techniques yielded significantly different results, depending on sampling conditions, underlining the need for a standardization of laboratory experiments to allow relevant comparisons of such techniques.

  6. Assessment of heat shock proteins and endothelial dysfunction in acute pulmonary embolism.

    Science.gov (United States)

    İn, Erdal; Deveci, Figen; Kaman, Dilara

    2016-06-01

    We determined the levels of some heat shock proteins (HSP27, HSP70, and HSP90), L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) levels in patients with acute pulmonary embolism. The present case-control study comprised a healthy control group (n = 57) and patients with acute pulmonary embolism (n = 84). HSPs, L-arginine, ADMA, and SDMA levels were measured in all of the cases. The mean age of the control group was 56.72 ± 8.44 years, and the mean age of the patients with acute pulmonary embolism was 60.20 ± 16.56 years (P = 0.104). Compared with controls, patients with acute pulmonary embolism had significantly higher mean serum HSP27, HSP90, and ADMA levels, whereas the mean serum L-arginine and SDMA levels were lower (P In patients with acute pulmonary embolism serum HSP27, HSP70, and ADMA levels were negatively correlated with partial pressures of arterial oxygen levels (r = -0.281, P = 0.01; r = -0.263, P = 0.016; and r = -0.275, P = 0.011, respectively) and arterial oxygen saturation (r = -0.225, P = 0.039; r = -0.400, P in acute pulmonary embolism.

  7. Role of platelets in maintenance of pulmonary vascular permeability to protein

    Energy Technology Data Exchange (ETDEWEB)

    Lo, S.K.; Burhop, K.E.; Kaplan, J.E.; Malik, A.B. (Albany Medical College of Union Univ., NY (USA))

    1988-04-01

    The authors examined the role of platelets in maintenance of pulmonary vascular integrity by inducing thrombocytopenia in sheep using antiplatelet serum (APS). A causal relationship between thrombocytopenia and increase in pulmonary vascular permeability was established by platelet repletion using platelet-rich plasma (PRP). Sheep were chronically instrumented and lung lymph fistulas prepared to monitor pulmonary lymph flow (Q{sub lym}). A balloon catheter was positioned in the left atrium to assess pulmonary vascular permeability to protein after raising the left atrial pressure (P{sub la}). Thrombocytopenia was maintained for 3 days by daily intramuscular APS injections. In studies using cultured bovine pulmonary artery endothelial monolayers, transendothelia permeability of {sup 125}I-labeled albumin was reduced 50 and 95%, respectively, when 2.5 {times} 10{sup 7} or 5 {times} 10{sup 7} platelets were added onto endothelial monolayers. However, addition of 5 {times} 10{sup 6} platelets or 5 {times} 10{sup 7} red blood cells did not reduce endothelial monolayer albumin permeability. Results indicate that platelets are required for the maintenance of pulmonary vascular permeability. Reduction in permeability appears to involve an interaction of platelets with the endothelium.

  8. Analysis of protein-protein interaction network in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Yuan, Y P; Shi, Y H; Gu, W C

    2014-10-31

    Chronic obstructive pulmonary disease (COPD) is a growing cause of morbidity and mortality throughout the world. The purpose of our study was to uncover biomarkers and explore its pathogenic mechanisms at the molecular level. The gene expression profiles of COPD samples and normal controls were downloaded from Gene Expression Omnibus. Matlab was used for data preprocessing and SAM4.0 was applied to determine the differentially expressed genes (DEGs). Furthermore, a protein-protein interaction (PPI) network was constructed by mapping the DEGs into PPI data, and functional analysis of the network was conducted with BiNGO. A total of 348 DEGs and 765 interactive genes were identified. The hub genes were mainly involved in metabolic processes and ribosome biogenesis. Several genes related to COPD in the PPI network were found, including CAMK1D, ALB, KIT, and DDX3Y. In conclusion, CAMK1D, ALB, KIT, and DDX3Y were chosen as candidate genes, which have the potential to be biomarkers or candidate target molecules to apply in clinical diagnosis and treatment of COPD.

  9. Adsorption of proteins at the solution/air interface influenced by added nonionic surfactants at very low concentrations for both components. 3. Dilational surface rheology.

    Science.gov (United States)

    Fainerman, V B; Aksenenko, E V; Lylyk, S V; Lotfi, M; Miller, R

    2015-03-05

    The influence of the addition of the nonionic surfactants C12DMPO, C14DMPO, C10OH, and C10EO5 at concentrations between 10(-5) and 10(-1) mmol/L to solutions of β-casein (BCS) and β-lactoglobulin (BLG) at a fixed concentration of 10(-5) mmol/L on the dilational surface rheology is studied. A maximum in the viscoelasticity modulus |E| occurs at very low surfactant concentrations (10(-4) to 10(-3) mmol/L) for mixtures of BCS with C12DMPO and C14DMPO and for mixtures of BLG with C10EO5, while for mixture of BCS with C10EO5 the value of |E| only slightly increased. The |E| values calculated with a recently developed model, which assumes changes in the interfacial molar area of the protein molecules due to the interaction with the surfactants, are in satisfactory agreement with experimental data. A linear dependence exists between the ratio of the maximum modulus for the mixture to the modulus of the single protein solution and the coefficient reflecting the influence of the surfactants on the adsorption activity of the protein.

  10. Liposomal dry powders as aerosols for pulmonary delivery of proteins

    OpenAIRE

    Lu, Dongmei; Hickey, Anthony J.

    2005-01-01

    The purpose of this research was to develop liposomal dry powder aerosols for protein delivery. The delivery of stable protein formulations is essential for protein subunit vaccine delivery, which requires local delivery to macrophages in the lungs. β-Glucuronidase (GUS) was used as a model protein to evaluate dry powder liposomes as inhaled delivery vehicles. Dimyristoyl phosphatylcholine:cholesterol (7∶3) was selected as the liposome composition. The lyophilization of liposomes, micronizati...

  11. Activity and biophysical inhibition resistance of a novel synthetic lung surfactant containing Super-Mini-B DATK peptide

    Directory of Open Access Journals (Sweden)

    Robert H. Notter

    2016-01-01

    Full Text Available Background/objectives. This study examines the surface activity, resistance to biophysical inhibition, and pulmonary efficacy of a synthetic lung surfactant containing glycerophospholipids combined with Super Mini-B (S-MB DATK, a novel and stable molecular mimic of lung surfactant protein (SP-B. The objective of the work is to test whether S-MB DATK synthetic surfactant has favorable biophysical and physiological activity for future use in treating surfactant deficiency or dysfunction in lung disease or injury.Methods. The structure of S-MB DATK peptide was analyzed by homology modeling and by FTIR spectroscopy. The in vitro surface activity and inhibition resistance of synthetic S-MB DATK surfactant was assessed in the presence and absence of albumin, lysophosphatidylcholine (lyso-PC, and free fatty acids (palmitoleic and oleic acid. Adsorption and dynamic surface tension lowering were measured with a stirred subphase dish apparatus and a pulsating bubble surfactometer (20 cycles/min, 50% area compression, 37 °C. In vivo pulmonary activity of S-MB DATK surfactant was measured in ventilated rabbits with surfactant deficiency/dysfunction induced by repeated lung lavages that resulted in arterial PO2 values <100 mmHg.Results. S-MB DATK surfactant had very high surface activity in all assessments. The preparation adsorbed rapidly to surface pressures of 46–48 mN/m at 37 °C (low equilibrium surface tensions of 22–24 mN/m, and reduced surface tension to <1 mN/m under dynamic compression on the pulsating bubble surfactometer. S-MB DATK surfactant showed a significant ability to resist inhibition by serum albumin, C16:0 lyso-PC, and free fatty acids, but surfactant inhibition was mitigated by increasing surfactant concentration. S-MB DATK synthetic surfactant quickly improved arterial oxygenation and lung compliance after intratracheal instillation to ventilated rabbits with severe surfactant deficiency.Conclusions. S-MB DATK is an active mimic

  12. Impact of SDS surfactant on the interactions of Cu(2+) ions with the amyloidogenic region of human prion protein.

    Science.gov (United States)

    Hecel, Aleksandra; Migliorini, Caterina; Valensin, Daniela; Luczkowski, Marek; Kozlowski, Henryk

    2015-08-01

    Prion diseases, known as Transmissible Spongiform Encephalopathies (TSEs), are a group of fatal neuronal, and to some extent infectious disorders, associated with a pathogenic protein agent called prion protein (PrP). The human prion protein (hPrP) fragment encompassing the 91-127 region, also known as the amyloidogenic domain, comprises two copper-binding sites corresponding to His-96 and His-111 residues that act as anchors for Cu(2+) binding. In this work, we investigated Cu(2+) interaction with hPrP91-127 in the presence of the anionic surfactant sodium dodecyl sulfate (SDS), which induces a partial α-helix folding of the peptide. Our data indicate that the Cu(2+) coordination ability of the amyloidogenic fragment in the presence of SDS micelles is significantly different to that observed in aqueous solution. This is mainly due to the fact that SDS micelles strongly stabilize the formation of the α-helical structure of the peptide backbone, which is well conserved also upon Cu(2+) binding, contrary to the random coil conformation mainly assumed by hPrP91-127 in aqueous solutions. Potentiometric and spectroscopic studies clearly indicate that in the case of SDS containing solutions, Cu(2+) ions coordinate simultaneously to both imidazoles, while in the case of water solutions, metal ion coordination involves only a single His side chain, which individually acts as an independent Cu(2+) anchoring site.

  13. Values of surfactant protein-A and surfactant protein-D in Interstitial lung disease%血清肺表面活性蛋白A、D在间质性肺疾病中的价值

    Institute of Scientific and Technical Information of China (English)

    刘晓立; 吕长俊; 王晓芝

    2008-01-01

    The pathological diagnosis of interstitial lung disease (ILD) by surgical lung biopsy is important for clinical decision. There is a need, however, to use serum markers which is non-invasive for differentiating ILD. Surfactant protein(SP)-A, SP-D are useful markers for the diagnosis and evaluation of activity of ILD. More studies have appeared on the proteins' usefulness in recent years and they are reviewed as follows.%开胸肺活检取得病理诊断是对间质性肺疾病(interstitial lung disease,ILD)的诊断起决定作用的.然而,需要一种非侵入性的血清标志物来区别ILD,尤其是对于最常见、预后最差的寻常型间质性肺炎.肺表面活性蛋白A、D在ILD鉴别诊断及评定疾病活动性上有提示意义.近年来这类蛋白的研究进展显著,现对ILD的价值作一综述.

  14. Innovation in surfactant therapy II: surfactant administration by aerosolization.

    Science.gov (United States)

    Pillow, J Jane; Minocchieri, S

    2012-01-01

    Instilled bolus surfactant is the only approved surfactant treatment for neonatal respiratory distress syndrome. However, recent trends towards increased utilization of noninvasive respiratory support for preterm infants with surfactant deficiency have created a demand for a similarly noninvasive means of administering exogenous surfactant. Past approaches to surfactant nebulization met with varying success due to inefficient aerosol devices resulting in low intrapulmonary delivery doses of surfactant with variable clinical effectiveness. The recent development of vibrating membrane nebulizers, coupled with appropriate positioning of the interface device, indicates that efficient delivery of aerosolized surfactant is now a realistic goal in infants. Evidence of clinical effect despite low total administered dose in pilot studies, together with suggestions of enhanced homogeneity of pulmonary distribution indicate that this therapy may be applied in a cost-effective manner, with minimal patient handling and disruption. These studies need to be subjected to appropriately designed randomized controlled trials. Further work is also required to determine the optimum delivery route (mask, intranasal prong, nasopharyngeal or laryngeal), dosing amount and redosing interval.

  15. Superficial disposition of the N-terminal region of the surfactant protein SP-C and the absence of specific SP-B-SP-C interactions in phospholipid bilayers

    DEFF Research Database (Denmark)

    Plasencia, I; Cruz, A; Casals, C;

    2001-01-01

    A dansylated form of porcine surfactant-associated protein C (Dns-SP-C), bearing a single dansyl group at its N-terminal end, has been used to characterize the lipid-protein and protein-protein interactions of SP-C reconstituted in phospholipid bilayers, using fluorescence spectroscopy. The fluor......A dansylated form of porcine surfactant-associated protein C (Dns-SP-C), bearing a single dansyl group at its N-terminal end, has been used to characterize the lipid-protein and protein-protein interactions of SP-C reconstituted in phospholipid bilayers, using fluorescence spectroscopy...... of the N-terminal segment of the protein into less polar environments that originate during protein lateral segregation. This suggests that conformation and interactions of the N-terminal segment of SP-C could be important in regulating the lateral distribution of the protein in surfactant bilayers...

  16. The impact of surfactant protein-A on ozone-induced changes in the mouse bronchoalveolar lavage proteome

    Directory of Open Access Journals (Sweden)

    Floros Joanna

    2009-03-01

    Full Text Available Abstract Background Ozone is a major component of air pollution. Exposure to this powerful oxidizing agent can cause or exacerbate many lung conditions, especially those involving innate immunity. Surfactant protein-A (SP-A plays many roles in innate immunity by participating directly in host defense as it exerts opsonin function, or indirectly via its ability to regulate alveolar macrophages and other innate immune cells. The mechanism(s responsible for ozone-induced pathophysiology, while likely related to oxidative stress, are not well understood. Methods We employed 2-dimensional difference gel electrophoresis (2D-DIGE, a discovery proteomics approach, coupled with MALDI-ToF/ToF to compare the bronchoalveolar lavage (BAL proteomes in wild type (WT and SP-A knockout (KO mice and to assess the impact of ozone or filtered air on the expression of BAL proteins. Using the PANTHER database and the published literature most identified proteins were placed into three functional groups. Results We identified 66 proteins and focused our analysis on these proteins. Many of them fell into three categories: defense and immunity; redox regulation; and protein metabolism, modification and chaperones. In response to the oxidative stress of acute ozone exposure (2 ppm; 3 hours there were many significant changes in levels of expression of proteins in these groups. Most of the proteins in the redox group were decreased, the proteins involved in protein metabolism increased, and roughly equal numbers of increases and decreases were seen in the defense and immunity group. Responses between WT and KO mice were similar in many respects. However, the percent change was consistently greater in the KO mice and there were more changes that achieved statistical significance in the KO mice, with levels of expression in filtered air-exposed KO mice being closer to ozone-exposed WT mice than to filtered air-exposed WT mice. Conclusion We postulate that SP-A plays a role

  17. Cardiorespiratory fitness, pulmonary function and C-reactive protein levels in nonsmoking individuals with diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Francisco, C.O.; Catai, A.M.; Moura-Tonello, S.C.G. [Universidade Federal de São Carlos, Departamento de Fisioterapia, São Carlos, SP, Brasil, Departamento de Fisioterapia, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Lopes, S.L.B. [Universidade Federal de São Carlos, Departamento de Medicina, São Carlos, SP, Brasil, Departamento de Medicina, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Benze, B.G. [Universidade Federal de São Carlos, Departamento de Estatística, São Carlos, SP, Brasil, Departamento de Estatística, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Del Vale, A.M.; Leal, A.M.O. [Universidade Federal de São Carlos, Departamento de Medicina, São Carlos, SP, Brasil, Departamento de Medicina, Universidade Federal de São Carlos, São Carlos, SP (Brazil)

    2014-04-15

    The objective of this study was to evaluate cardiorespiratory fitness and pulmonary function and the relationship with metabolic variables and C-reactive protein (CRP) plasma levels in individuals with diabetes mellitus (DM). Nineteen men with diabetes and 19 age- and gender-matched control subjects were studied. All individuals were given incremental cardiopulmonary exercise and pulmonary function tests. In the exercise test, maximal workload (158.3±22.3 vs 135.1±25.2, P=0.005), peak heart rate (HR{sub peak}: 149±12 vs 139±10, P=0.009), peak oxygen uptake (VO{sub 2peak}: 24.2±3.2 vs 18.9±2.8, P<0.001), and anaerobic threshold (VO{sub 2VT}: 14.1±3.4 vs 12.2±2.2, P=0.04) were significantly lower in individuals with diabetes than in control subjects. Pulmonary function test parameters, blood pressure, lipid profile (triglycerides, HDL, LDL, and total cholesterol), and CRP plasma levels were not different in control subjects and individuals with DM. No correlations were observed between hemoglobin A1C (HbA1c), CRP and pulmonary function test and cardiopulmonary exercise test performance. In conclusion, the results demonstrate that nonsmoking individuals with DM have decreased cardiorespiratory fitness that is not correlated with resting pulmonary function parameters, HbA1c, and CRP plasma levels.

  18. Bone morphogenetic protein receptor II regulates pulmonary artery endothelial cell barrier function.

    Science.gov (United States)

    Burton, Victoria J; Ciuclan, Loredana I; Holmes, Alan M; Rodman, David M; Walker, Christoph; Budd, David C

    2011-01-06

    Mutations in bone morphogenetic protein receptor II (BMPR-II) underlie most heritable cases of pulmonary arterial hypertension (PAH). However, less than half the individuals who harbor mutations develop the disease. Interestingly, heterozygous null BMPR-II mice fail to develop PAH unless an additional inflammatory insult is applied, suggesting that BMPR-II plays a fundamental role in dampening inflammatory signals in the pulmonary vasculature. Using static- and flow-based in vitro systems, we demonstrate that BMPR-II maintains the barrier function of the pulmonary artery endothelial monolayer suppressing leukocyte transmigration. Similar findings were also observed in vivo using a murine model with loss of endothelial BMPR-II expression. In vitro, the enhanced transmigration of leukocytes after tumor necrosis factor α or transforming growth factor β1 stimulation was CXCR2 dependent. Our data define how loss of BMPR-II in the endothelial layer of the pulmonary vasculature could lead to a heightened susceptibility to inflammation by promoting the extravasation of leukocytes into the pulmonary artery wall. We speculate that this may be a key mechanism involved in the initiation of the disease in heritable PAH that results from defects in BMPR-II expression.

  19. Circulating surfactant protein D is associated to mortality in elderly women

    DEFF Research Database (Denmark)

    Johansson, Helle Wulf; Thinggaard, M.; Tan, Q.;

    2013-01-01

    2100ng/ml had significantly increased mortality when compared to elderly women with SP-D levels equal to or below 2100ng/ml (HR, 1.45; 95% CI, 1.12-1.88; p=0.005). The likelihood that the female twin with the highest SP-D level died first increased with increasing SP-D levels (p=0.031) - that is......, the bigger intra-pair difference in SP-D level, the higher the probability that the twin with the highest measure died first (odds ratio [OR], 1.66; p=0.047). CONCLUSION: The study demonstrates that higher circulating SP-D levels are associated with increased mortality rate in elderly women...... in this population-based cohort study. SP-D may serve as a biomarker to track the cardio-pulmonary health status in elderly women....

  20. Liposomal dry powders as aerosols for pulmonary delivery of proteins.

    Science.gov (United States)

    Lu, Dongmei; Hickey, Anthony J

    2005-12-21

    The purpose of this research was to develop liposomal dry powder aerosols for protein delivery. The delivery of stable protein formulations is essential for protein subunit vaccine delivery, which requires local delivery to macrophages in the lungs. Beta-glucuronidase (GUS) was used as a model protein to evaluate dry powder liposomes as inhaled delivery vehicles. Dimyristoyl phosphatylcholine:cholesterol (7:3) was selected as the liposome composition. The lyophilization of liposomes, micronization of the powders, aerosolization using a dry powder inhaler (DPI), and in vitro aerodynamic fine particle fraction upon collection in a twin-stage liquid impinger were evaluated. After lyophilization and jet-milling, the total amount of GUS and its activity, representing encapsulation efficiency and stability, were evaluated. The GUS amount and activity were measured and compared with freshly-prepared liposomes in the presence of mannitol, 43% of initial GUS amount, 29% of GUS activity after lyophilization and 36% of GUS amount, 22% of activity after micronization were obtained. Emitted doses from dry powder inhaler were 53%, 58%, 66%, and 73% for liposome powder:mannitol carrier ratios of 1:0, 1:4, 1:9, and 1:19. Fifteen percent of the liposome particles were less than 6.4 mum in aerodynamic diameter. The results demonstrate that milled liposome powders containing protein molecules can be aerosolized effectively at a fixed flow rate. Influences of different cryoprotectants on lyophilization of protein liposome formulations are reported. The feasibility of using liposomal dry powder aerosols for protein delivery has been demonstrated but further optimization is required in the context of specific therapeutic proteins.

  1. Sex differences in the response of the alveolar macrophage proteome to treatment with exogenous surfactant protein-A

    Directory of Open Access Journals (Sweden)

    Phelps David S

    2012-07-01

    Full Text Available Abstract Background Male wild type (WT C57BL/6 mice are less capable of clearing bacteria and surviving from bacterial pneumonia than females. However, if an oxidative stress (acute ozone exposure occurs before infection, the advantage shifts to males who then survive at higher rates than females. We have previously demonstrated that survival in surfactant protein-A (SP-A knockout (KO mice compared to WT was significantly reduced. Because the alveolar macrophage (AM is pivotal in host defense we hypothesized that SP-A and circulating sex hormones are responsible for these sex differences. We used 2D-DIGE to examine the relationship of sex and SP-A on the AM proteome. The role of SP-A was investigated by treating SP-A KO mice with exogenous SP-A for 6 and 18 hr and studying its effects on the AM proteome. Results We found: 1 less variance between KO males and females than between the WT counterparts by principal component analysis, indicating that SP-A plays a role in sex differences; 2 fewer changes in females when the total numbers of significantly changing protein spots or identified whole proteins in WT or 18 hr SP-A-treated males or females were compared to their respective KO groups; 3 more proteins with functions related to chaperones or protease balance and Nrf2-regulated proteins changed in response to SP-A in females than in males; and 4 the overall pattern of SP-A induced changes in actin-related proteins were similar in both sexes, although males had more significant changes. Conclusions Although there seems to be an interaction between sex and the effect of SP-A, it is unclear what the responsible mechanisms are. However, we found that several of the proteins that were expressed at significantly higher levels in females than in males in WT and/or in KO mice are known to interact with the estrogen receptor and may thus play a role in the SP-A/sex interaction. These include major vault protein, chaperonin subunit 2 (beta (CCT2, and Rho

  2. Pulmonary alveolar proteinosis

    Directory of Open Access Journals (Sweden)

    B. Crestani

    2011-06-01

    Full Text Available Pulmonary alveolar proteinosis (PAP is a rare pulmonary disease characterised by alveolar accumulation of surfactant. It may result from mutations in surfactant proteins or granulocyte macrophage-colony stimulating factor (GM-CSF receptor genes, it may be secondary to toxic inhalation or haematological disorders, or it may be auto-immune, with anti-GM-CSF antibodies blocking activation of alveolar macrophages. Auto-immune alveolar proteinosis is the most frequent form of PAP, representing 90% of cases. Although not specific, high-resolution computed tomography shows a characteristic “crazy paving” pattern. In most cases, bronchoalveolar lavage findings establish the diagnosis. Whole lung lavage is the most effective therapy, especially for auto-immune disease. Novel therapies targeting alveolar macrophages (recombinant GM-CSF therapy or anti-GM-CSF antibodies (rituximab and plasmapheresis are being investigated. Our knowledge of the pathophysiology of PAP has improved in the past 20 yrs, but therapy for PAP still needs improvement.

  3. Antimicrobial proteins and polypeptides in pulmonary innate defence

    Directory of Open Access Journals (Sweden)

    Taggart Clifford C

    2006-02-01

    Full Text Available Abstract Inspired air contains a myriad of potential pathogens, pollutants and inflammatory stimuli. In the normal lung, these pathogens are rarely problematic. This is because the epithelial lining fluid in the lung is rich in many innate immunity proteins and peptides that provide a powerful anti-microbial screen. These defensive proteins have anti-bacterial, anti- viral and in some cases, even anti-fungal properties. Their antimicrobial effects are as diverse as inhibition of biofilm formation and prevention of viral replication. The innate immunity proteins and peptides also play key immunomodulatory roles. They are involved in many key processes such as opsonisation facilitating phagocytosis of bacteria and viruses by macrophages and monocytes. They act as important mediators in inflammatory pathways and are capable of binding bacterial endotoxins and CPG motifs. They can also influence expression of adhesion molecules as well as acting as powerful anti-oxidants and anti-proteases. Exciting new antimicrobial and immunomodulatory functions are being elucidated for existing proteins that were previously thought to be of lesser importance. The potential therapeutic applications of these proteins and peptides in combating infection and preventing inflammation are the subject of ongoing research that holds much promise for the future.

  4. Switchable Surfactants

    National Research Council Canada - National Science Library

    Yingxin Liu; Philip G. Jessop; Michael Cunningham; Charles A. Eckert; Charles L. Liotta

    2006-01-01

    .... We report that long-chain alkyl amidine compounds can be reversibly transformed into charged surfactants by exposure to an atmosphere of carbon dioxide, thereby stabilizing water/alkane emulsions...

  5. Upregulation of Steroidogenic Acute Regulatory Protein by Hypoxia Stimulates Aldosterone Synthesis in Pulmonary Artery Endothelial Cells to Promote Pulmonary Vascular Fibrosis

    Science.gov (United States)

    Maron, Bradley A.; Oldham, William M.; Chan, Stephen Y.; Vargas, Sara O.; Arons, Elena; Zhang, Ying-Yi; Loscalzo, Joseph; Leopold, Jane A.

    2014-01-01

    Background The molecular mechanism(s) regulating hypoxia-induced vascular fibrosis are unresolved. Hyperaldosteronism correlates positively with vascular remodeling in pulmonary arterial hypertension (PAH), suggesting that aldosterone may contribute to the pulmonary vasculopathy of hypoxia. The hypoxia-sensitive transcription factors c-Fos/c-Jun regulate steroidogenic acute regulatory protein (StAR), which facilitates the rate-limiting step of aldosterone steroidogenesis. We hypothesized that c-Fos/c-Jun upregulation by hypoxia activates StAR-dependent aldosterone synthesis in human pulmonary artery endothelial cells (HPAECs) to promote vascular fibrosis in PAH. Methods and Results Patients with PAH, rats with Sugen/hypoxia-PAH, and mice exposed to chronic hypoxia expressed increased StAR in remodeled pulmonary arterioles, providing a basis for investigating hypoxia-StAR signaling in HPAECs. Hypoxia (2.0% FiO2) increased aldosterone levels selectively in HPAECs, which was confirmed by liquid chromatography-mass spectrometry. Increased aldosterone by hypoxia resulted from enhanced c-Fos/c-Jun binding to the proximal activator protein (AP-1) site of the StAR promoter in HPAECs, which increased StAR expression and activity. In HPAECs transfected with StAR-siRNA or treated with the AP-1 inhibitor, SR-11302, hypoxia failed to increase aldosterone, confirming that aldosterone biosynthesis required StAR activation by c-Fos/c-Jun. The functional consequences of aldosterone were confirmed by pharmacological inhibition of the mineralocorticoid receptor with spironolactone or eplerenone, which attenuated hypoxia-induced upregulation of the fibrogenic protein connective tissue growth factor and collagen III in vitro, and decreased pulmonary vascular fibrosis to improve pulmonary hypertension in Conclusions Our findings identify autonomous aldosterone synthesis in HPAECs due to hypoxia-mediated upregulation of StAR as a novel molecular mechanism that promotes pulmonary vascular

  6. Effects of the Biomolecules: Vitamins, Proteins, Amino Acids, and Surfactants: DTAB, MTOAC, TMSOI, Orcinol on Upper Critical Solution Temperatures

    Directory of Open Access Journals (Sweden)

    Vinod Kumar

    2007-09-01

    Full Text Available Upper critical solution temperatures (UCSTS ± 0.05 K and mutual solubilities of phenol + water systems are reported separately with 0.5 millimol kg-1 (mm kg-1 proteins (casein, pepsin, egg-albumin, vitamins (B1-thiamine, B2-riboflavin, B6-pyridoxine, amino acids (glycine, β-alanine, L-leucine and surfactants (dodecyl trimethylammonium bromide- DTAB, trimethylsulphoxonium iodide-TMSOI, methyltrioctylammonium chloride- MTOAC, orcinol. The additives decrease the UCSTs by about 0.50-2 0C with slight enhancement in mutual solubilities but the leucine with two –CH3 (methyl and two - CH2- (methylene groups produce negligible increase in the solubilities. The –CH3 and - CH2- groups develop stronger hydrophobic interactions but the glycine develops stronger hydrophilic interactions due to –N+H3 (amino and –COO- (carboxylic groups and weaker hydrophobic due to single –CH2- group. The leucine increases the solubility by 0.009 mole fractions with a 0.7 0C decrease in USCT as compared to phenol-water. The mole fractions of additives restricted to 0.002 to 0.005 range, the conjugations of casein and vitamins in place of –CH3 groups of amino acids enhance the solubility with lower UCST values.

  7. 不同类型表面活性剂与蛋白质作用研究进展%Research Progress of the Interaction of Different Type Surfactants with Proteins

    Institute of Scientific and Technical Information of China (English)

    曹洪玉; 张莹莹; 唐乾; 郑学仿

    2014-01-01

    Surfactants interact with proteins in multifarious ways which depend on surfactant types, concentration, structure, and physical-chemical properties. To obtain a global overview of this process, the physicochemical properties of the interaction was began with introducing between proteins and surfactants, the recent research including the structural properties of protein-surfactant complex, the adsorption mechanisms of the complex, as well as the structural changes of proteins induced by surfactants. Then different phase behaviors and interaction mechanisms of proteins interaction were expounded with five different classes of surfactants, including anionic surfactants, cationic surfactants, zwitterionic surfactants, non-ionic surfactants, fluorine and Gemini surfactants. Recent research scope and current situation in every field had also been reviewed. Our results and methods in studying protein-surfactant interaction were systematically summarized in the suitable part.%表面活性剂和蛋白质作用的方式与表面活性剂的种类、结构、浓度和其理化性质有关。本文系统地总结了多种类型表面活性剂(阴离子型、阳离子型、两性离子型、非离子型、氟表面活性剂及 Gemini 表面活性剂)的结构特点,以蛋白质-表面活性剂相互作用的物理化学特征为出发点,综述了该体系相互作用的最新研究成果及进展,包括二者作用时所形成的复合物的结构理论,复合物的吸附机理及其作用过程中蛋白质结构的变化;结合本课题组的工作总结分析了蛋白质分别与各类表面活性剂相互作用过程中作用力特征、相行为、作用机理及应用。

  8. Protein–Protein Interaction between Surfactant Protein D and DC-SIGN via C-Type Lectin Domain Can Suppress HIV-1 Transfer

    Directory of Open Access Journals (Sweden)

    Eswari Dodagatta-Marri

    2017-07-01

    Full Text Available Surfactant protein D (SP-D is a soluble C-type lectin, belonging to the collectin (collagen-containing calcium-dependent lectin family, which acts as an innate immune pattern recognition molecule in the lungs at other mucosal surfaces. Immune regulation and surfactant homeostasis are salient functions of SP-D. SP-D can bind to a range of viral, bacterial, and fungal pathogens and trigger clearance mechanisms. SP-D binds to gp120, the envelope protein expressed on HIV-1, through its C-type lectin or carbohydrate recognition domain. This is of importance since SP-D is secreted by human mucosal epithelial cells and is present in the female reproductive tract, including vagina. Another C-type lectin, dendritic cell (DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN, present on the surface of the DCs, also binds to HIV-1 gp120 and facilitates viral transfer to the lymphoid tissues. DCs are also present at the site of HIV-1 entry, embedded in vaginal or rectal mucosa. In the present study, we report a direct protein–protein interaction between recombinant forms of SP-D (rfhSP-D and DC-SIGN via their C-type lectin domains. Both SP-D and DC-SIGN competed for binding to immobilized HIV-1 gp120. Pre-incubation of human embryonic kidney cells expressing surface DC-SIGN with rfhSP-D significantly inhibited the HIV-1 transfer to activated peripheral blood mononuclear cells. In silico analysis revealed that SP-D and gp120 may occupy same sites on DC-SIGN, which may explain the reduced transfer of HIV-1. In summary, we demonstrate, for the first time, that DC-SIGN is a novel binding partner of SP-D, and this interaction can modulate HIV-1 capture and transfer to CD4+ T cells. In addition, the present study also reveals a novel and distinct mechanism of host defense by SP-D against HIV-1.

  9. Alterations of the murine gut microbiome in allergic airway disease are independent of surfactant protein D

    DEFF Research Database (Denmark)

    Barfod, Kenneth Klingenberg; Roggenbuck, Michael; Al-Shuweli, Suzan

    2017-01-01

    on microbiota and interfere with the interpretation of immunological data from the model. Generally, little is known about the effect of the SP-D protein in itself and in combination with airway disease on the microbiota. In this study, we tested the hypothesis that microbiome composition would change......Background SP-D is an important host defense lectin in innate immunity and SP-D deficient mice show several abnormal immune effects and are susceptible to allergen-induced airway disease. At the same time, host microbiome interactions play an important role in the development of allergic airway...

  10. Study of the binding between lysozyme and C10-TAB: determination and interpretation of the partial properties of protein and surfactant at infinite dilution.

    Science.gov (United States)

    Morgado, Jorge; Aquino-Olivos, Marco Antonio; Martínez-Hernández, Ranulfo; Corea, Mónica; Grolier, Jean Pierre E; del Río, José Manuel

    2008-06-01

    This work examines the binding in aqueous solution, through the experimental determination of specific volumes and specific adiabatic compressibility coefficients, of decyltrimethylammonium bromide to lysozyme and to non-charged polymeric particles (which have been specially synthesized by emulsion polymerization). A method was developed to calculate the specific partial properties at infinite dilution and it was shown that a Gibbs-Duhem type equation holds at this limit for two solutes. With this equation, it is possible to relate the behavior of the partial properties along different binding types at a constant temperature. It was found that the first binding type, specific with high affinity, is related to a significant reduction of surfactant compressibility. The second binding type is accompanied by the unfolding of the protein and the third one is qualitatively identical to the binding of the surfactant to non-charged polymeric particles.

  11. Polymorphisms in the surfactant protein a gene are associated with the susceptibility to recurrent urinary tract infection in chinese women.

    Science.gov (United States)

    Liu, Jiao; Hu, Fengqi; Liang, Wei; Wang, Guirong; Singhal, Pravin C; Ding, Guohua

    2010-05-01

    Some risk factors for susceptibility to recurrent urinary tract infection (r-UTI) are well known, but the genetic role in acquiring the disease is poorly understood. Surfactant protein A and D (SP-A and SP-D) play an important role in modulation of lung inflammatory processes. The SP-A1 and SP-A2 genes encoding SP-A and the SP-D gene are highly polymorphic, and some of polymorphisms are associated with several infective diseases, including pyelonephritis. In the present study, we investigated whether some of these polymorphisms are associated with the risk of r-UTI in Chinese population. Genomic DNA was extracted from blood samples of 32 female patients with r-UTI and 30 age-matched, unrelated healthy female subjects. Genotyping of gene polymorphisms was analyzed by PCR. Among 11 single nucleotide polymorphisms (SNPs) (five of SP-A1, four of SP-A2 and two of SP-D) observed in the enrolled subjects, Ala19Val of SP-A1 and Lys223Gln of SP-A2 were associated with susceptibility to r-UTI. The frequencies of 19Ala allele of SP-A1 gene (p = 0.038) and 223Gln allele of SP-A2 gene (p = 0.012) in the patients were significantly higher than those in healthy subjects. The serum SP-A and SP-D levels were increased and the urine SP-A and SP-D levels were decreased in r-UTI patients compared with control subjects (p UTI patients with 19Ala/Ala or 223Gln/Gln genotype were associated with high serum and low urine SP-A levels (p UTI.

  12. Comparison of surfactant protein B polymorphisms of healthy term newborns with preterm newborns having respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    P.P.R. Lyra

    2007-06-01

    Full Text Available Polymorphisms and mutations in the surfactant protein B (SP-B gene have been associated with the pathogenesis of respiratory distress syndrome (RDS. The objective of the present study was to compare the frequencies of SP-B gene polymorphisms between preterm babies with RDS and healthy term newborns. We studied 50 preterm babies with RDS (inclusion criteria - newborns with RDS and gestational age between 28 and 33 weeks and 6 days, and 100 healthy term newborns. Four SP-B gene polymorphisms were analyzed: A/C at nucleotide -18, C/T at nucleotide 1580, A/G at nucleotide 9306, and G/C at nucleotide 8714, by PCR amplification of genomic DNA and genotyping by cRFLP. The healthy newborns comprised 42 female and 58 male neonates; 39 were white and 61 non-white. The RDS group comprised 21 female and 29 male preterm neonates; 28 were white and 22 non-white. Weight ranged from 640 to 2080 g (mean: 1273 g; mean gestational age was 31 weeks and 2 days (range: 28-33 weeks and 6 days. When white children were analyzed separately, a statistically significant difference in the G/C polymorphism at 8714 was observed between groups (P = 0.028. All other genotype frequencies were similar for both groups when sex and race were analyzed together. Analysis of the SP-B polymorphism G/C at nucleotide 8714 showed that among white neonates the GG genotype was found only in the RDS group at a frequency of 17% and the GC genotype was more frequently found in healthy term newborns. These data demonstrate an association of GG genotype with RDS.

  13. Comparison of surfactant protein B polymorphisms of healthy term newborns with preterm newborns having respiratory distress syndrome.

    Science.gov (United States)

    Lyra, P P R; Vaz, F A C; Moreira, P E; Hoffmann, J W; Demello, D E; Diniz, E M A

    2007-06-01

    Polymorphisms and mutations in the surfactant protein B (SP-B) gene have been associated with the pathogenesis of respiratory distress syndrome (RDS). The objective of the present study was to compare the frequencies of SP-B gene polymorphisms between preterm babies with RDS and healthy term newborns. We studied 50 preterm babies with RDS (inclusion criteria - newborns with RDS and gestational age between 28 and 33 weeks and 6 days), and 100 healthy term newborns. Four SP-B gene polymorphisms were analyzed: A/C at nucleotide -18, C/T at nucleotide 1580, A/G at nucleotide 9306, and G/C at nucleotide 8714, by PCR amplification of genomic DNA and genotyping by cRFLP. The healthy newborns comprised 42 female and 58 male neonates; 39 were white and 61 non-white. The RDS group comprised 21 female and 29 male preterm neonates; 28 were white and 22 non-white. Weight ranged from 640 to 2080 g (mean: 1273 g); mean gestational age was 31 weeks and 2 days (range: 28-33 weeks and 6 days). When white children were analyzed separately, a statistically significant difference in the G/C polymorphism at 8714 was observed between groups (P = 0.028). All other genotype frequencies were similar for both groups when sex and race were analyzed together. Analysis of the SP-B polymorphism G/C at nucleotide 8714 showed that among white neonates the GG genotype was found only in the RDS group at a frequency of 17% and the GC genotype was more frequently found in healthy term newborns. These data demonstrate an association of GG genotype with RDS.

  14. Common genetic variants of surfactant protein-D (SP-D are associated with type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Neus Pueyo

    Full Text Available CONTEXT: Surfactant protein-D (SP-D is a primordial component of the innate immune system intrinsically linked to metabolic pathways. We aimed to study the association of single nucleotide polymorphisms (SNPs affecting SP-D with insulin resistance and type 2 diabetes (T2D. RESEARCH DESIGN AND METHODS: We evaluated a common genetic variant located in the SP-D coding region (rs721917, Met(31Thr in a sample of T2D patients and non-diabetic controls (n = 2,711. In a subset of subjects (n = 1,062, this SNP was analyzed in association with circulating SP-D concentrations, insulin resistance, and T2D. This SNP and others were also screened in the publicly available Genome Wide Association (GWA database of the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC. RESULTS: We found the significant association of rs721917 with circulating SP-D, parameters of insulin resistance and T2D. Indeed, G carriers showed decreased circulating SP-D (p = 0.004, decreased fasting glucose (p = 0.0002, glycated hemoglobin (p = 0.0005, and 33% (p = 0.002 lower prevalence of T2D, estimated under a dominant model, especially among women. Interestingly, these differences remained significant after controlling for origin, age, gender, and circulating SP-D. Moreover, this SNP and others within the SP-D genomic region (i.e. rs10887344 were significantly associated with quantitative measures of glucose homeostasis, insulin sensitivity, and T2D, according to GWAS datasets from MAGIC. CONCLUSIONS: SP-D gene polymorphisms are associated with insulin resistance and T2D. These associations are independent of circulating SP-D concentrations.

  15. Non-ionic Surfactants and Non-Catalytic Protein Treatment on Enzymatic Hydrolysis of Pretreated Creeping Wild Ryegrass

    Science.gov (United States)

    Zheng, Yi; Pan, Zhongli; Zhang, Ruihong; Wang, Donghai; Jenkins, Bryan

    Our previous research has shown that saline Creeping Wild Ryegrass (CWR), Leymus triticoides, has a great potential to be used for bioethanol production because of its high fermentable sugar yield, up to 85% cellulose conversion of pretreated CWR. However, the high cost of enzyme is still one of the obstacles making large-scale lignocellulosic bioethanol production economically difficult. It is desirable to use reduced enzyme loading to produce fermentable sugars with high yield and low cost. To reduce the enzyme loading, the effect of addition of non-ionic surfactants and non-catalytic protein on the enzymatic hydrolysis of pretreated CWR was investigated in this study. Tween 20, Tween 80, and bovine serum albumin (BSA) were used as additives to improve the enzymatic hydrolysis of dilute sulfuric-acid-pretreated CWR. Under the loading of 0.1 g additives/g dry solid, Tween 20 was the most effective additive, followed by Tween 80 and BSA. With the addition of Tween 20 mixed with cellulase loading of 15 FPU/g cellulose, the cellulose conversion increased 14% (from 75 to 89%), which was similar to that with cellulase loading of 30 FPU/g cellulose and without additive addition. The results of cellulase and BSA adsorption on the Avicel PH101, pretreated CWR, and lignaceous residue of pretreated CWR support the theory that the primary mechanism behind the additives is prevention of non-productive adsorption of enzymes on lignaceous material of pretreated CWR. The addition of additives could be a promising technology to improve the enzymatic hydrolysis by reducing the enzyme activity loss caused by non-productive adsorption.

  16. Surfactant replacement therapy for preterm and term neonates with respiratory distress.

    Science.gov (United States)

    Polin, Richard A; Carlo, Waldemar A

    2014-01-01

    Respiratory failure secondary to surfactant deficiency is a major cause of morbidity and mortality in preterm infants. Surfactant therapy substantially reduces mortality and respiratory morbidity for this population. Secondary surfactant deficiency also contributes to acute respiratory morbidity in late-preterm and term neonates with meconium aspiration syndrome, pneumonia/sepsis, and perhaps pulmonary hemorrhage; surfactant replacement may be beneficial for these infants. This statement summarizes the evidence regarding indications, administration, formulations, and outcomes for surfactant-replacement therapy. The clinical strategy of intubation, surfactant administration, and extubation to continuous positive airway pressure and the effect of continuous positive airway pressure on outcomes and surfactant use in preterm infants are also reviewed.

  17. Interleukin-12 suppresses filaria-induced pulmonary eosinophilia, deposition of major basic protein and airway hyperresponsiveness.

    Science.gov (United States)

    Mehlotra, R K; Hall, L R; Higgins, A W; Dreshaj, I A; Haxhiu, M A; Kazura, J W; Pearlman, E

    1998-10-01

    Tropical Pulmonary Eosinophilia (TPE) is a severe form of allergic asthma caused by the host inflammatory response to filarial helminths in the lung microvasculature, and is characterized by pulmonary eosinophilia, increased filarial-specific IgG and IgE antibodies, and airway hyperresponsiveness. The current study examined the effect of IL-12 on pulmonary eosinophilia, deposition of eosinophil major basic protein and airway hyperresponsiveness in mice inoculated i.v. with Brugia malayi microfilariae. Injection of recombinant murine IL-12 modulated the T helper (Th) response in the lungs from Th2- to Th1-like, with elevated IFN-gamma, and decreased IL-4 and IL-5 production. Consistent with this shift in cytokine response, antigen-specific IgG2a was elevated, and IgG1 and total serum IgE were decreased. In addition, eosinophils in BAL fluid from IL-12 treated mice were reduced from 56% to 11%, and there was no detectable MBP on respiratory epithelial cells. Importantly, IL-12 suppressed airway hyperresponsiveness compared with saline-injected control animals. Taken together, these data clearly demonstrate that by modulating Th associated cytokine production, IL-12 down-regulates filaria-induced lung immunopathology.

  18. Effect of pulmonary surfactant on late preterm infants with respiratory distress syndrome%肺表面活性物质治疗晚期早产儿呼吸窘迫综合征疗效观察

    Institute of Scientific and Technical Information of China (English)

    刘超; 张桂欣

    2012-01-01

    Objective To explore the curative effect of pulmonary surfactant in treatment of late preterm infants with respiratory distress syndrome (RDS). Methods Seventy-four late preterm infants with RDS were divided into two groups. Thirty-six patients in control group were treated with mechanical ventilation, infection prevention, prevention of brain injury, en-teral and parenteral nutrition; based on this, thirty-eight patients in observation group were treated with pulmonary surfactant through intratracheal instillation. The blood gas analysis was performed before treatment and six, twenty-four, forty-eight hours after treatment in two groups;and the curative effect was evaluated. Results There was no significant difference in the clinical effect between two groups (P >0. 05) . Before treatment, there was no significant difference in the indexes of arterial blood gas analysis between two groups(P >0.05). After treatment, the index of arterial blood gas analysis improved significantly in two groups(P < 0. 05,P < 0. 01) ,but the improvement was more in observation group( P <0.05). Conclusion Pulmonary surfactant can effectively improve hyoxemia in late preterm infants with RDS.%目的 探讨肺表面活性物质治疗晚期早产儿呼吸窘迫综合征(RDS)的疗效.方法 74例晚期早产儿RDS分为2组,对照组36例给予机械通气、预防感染和脑损伤、肠内和肠外营养支持等治疗,观察组38例在此基础上给予肺表面活性物质气管内滴入治疗;2组患者分别于治疗前及治疗6、24、48 h进行血气分析,并判定疗效.结果 2组临床疗效比较差异无统计学意义(P>0.05);2组患儿治疗前动脉血气分析指标比较差异均无统计学意义(P>0.05),2组患儿治疗后动脉血气分析指标均有显著改善(P <0.05,P<0.01),观察组改善更显著(P<0.05).结论 肺表面活性物质治疗晚期早产儿RDS可以有效改善低氧血症.

  19. Lung surfactant: Function and composition in the context of development and respiratory physiology.

    Science.gov (United States)

    Bernhard, Wolfgang

    2016-11-01

    Lung surfactant is a complex with a unique phospholipid and protein composition. Its specific function is to reduce surface tension at the pulmonary air-liquid interface. The underlying Young-Laplace equation, applying to the surface of any geometrical structure, is the more important the smaller its radii are. It therefore applies to the alveoli and bronchioli of mature lungs, as well as to the tubules and saccules of immature lungs. Surfactant comprises 80% phosphatidylcholine (PC), of which dipalmitoyl-PC, palmitoyl-myristoyl-PC and palmitoyl-palmitoleoyl-PC together are 75%. Anionic phosphatidylglycerol and cholesterol are about 10% each, whereas surfactant proteins SP-A to -D comprise 2-5%. Maturation of the surfactant system is not essentially due to increased synthesis but to decreased turnover of specific components. Molecular differences correlate with resting respiratory rate (RR), where PC16:0/16:0 is the lower the higher RR is. PC16:0/14:0 is increased during alveolar formation, and decreases immune reactions that might impair alveolar development. In rigid bird lungs, with air-capillaries rather than alveoli, and no surface area changes during the respiratory cycle, PC16:0/16:0 is highest and PC16:0/14:0 absent. As there is no need for a surface-associated surfactant reservoir, SP-C is absent in birds as well. Airflow is lowest and particle sedimentation highest in the extrapulmonary air-sacs, rather than in the gas-exchange area. Consequently, SP-A and -D for particle opsonization are absent in bird surfactant. In essence, comparative analysis is consistent with the concept that surfactant is adapted to the physiologic needs of a given vertebrate species at a given developmental stage.

  20. CPAP联合肺表面活性物质治疗早产儿呼吸困难疗效观察%Efficacy Observation on CPAP Combined with Pulmonary Surfactant for Dyspnea of Premature Infant

    Institute of Scientific and Technical Information of China (English)

    陈跃宣

    2015-01-01

    目的:探讨持续气道正压通气(CPAP)联合肺表面活性物质(珂立苏)治疗早产儿呼吸窘迫综合征(NRDS)的疗效。方法:36例呼吸困难早产儿早期均采用CPAP联合珂立苏肺表面活性物质治疗,观察患儿治疗前后的CPAP参数及临床症状的变化。结果:33例患儿治疗后呼吸困难状况得到明显改善,X线片亦显示病情明显好转;治疗2小时后,患儿的FiO2、PEEP均较治疗前显著改善(P<0.05)。结论:CPAP联合肺表面活性物质早期治疗NRDS早产儿疗效显著,可减少并发症的发生,且对胎龄<32周的早产儿疗效更佳。%Objective:To investigate the efficacy of continuous positive-pressure ventilation (CPAP) combined with pulmonary surfactant (Calsurf) for neonatal respiratory distress syndrome (NRDS). Methods:36 cases of premature infants with NRDS were all treated by CPAP combined with Cal-surf, observed the change of CPAP parameters and clinlcal symptoms before and after treatment. Results:After treatment, the dyspnea status in 33 cases of children had significantly improved, the X ray also showed that their illness had significantly turned better;2 hours after treatment, com-pared with those of before treatment, the FiO2 and PEEP of all of the children had significantly improved (P<0.05). Conclusion:The treatment of CPAP combined with pulmonary surfactant has significant curative effect on premature infants with NRDS, which can reduce the occurrence of com-plications, and the efficacy would be better if the age of premature infant is less than 32 weeks.

  1. Surfactant protein D of the innate immune defence is inversely associated with human obesity and SP-D deficiency infers increased body weight in mice

    DEFF Research Database (Denmark)

    Sorensen, G.L.; Hjelmborg, J.V.B.; Leth-Larsen, R.

    2006-01-01

    Surfactant protein D (SP-D) is a key regulator of pathogen-induced inflammation. SP-D is further involved in lipid homeostasis in mouse lung and circulation and recent data have demonstrated that the body mass index (BMI; in kg/m(2)) is influenced by genes in common with SP-D. The objective of th.......0001) in males on normal chow. Fat percentage was significantly increased by 17% in the Spd-/- male mice (P = 0.003). We conclude, that there is an association between low levels or absent SP-D and obesity....

  2. Surfactant Protein A and B Gene Polymorphisms and Risk of Respiratory Distress Syndrome in Late-Preterm Neonates

    Science.gov (United States)

    Tsitoura, Maria-Eleni I.; Stavrou, Eleana F.; Maraziotis, Ioannis A.; Sarafidis, Kosmas; Athanassiadou, Aglaia; Dimitriou, Gabriel

    2016-01-01

    Background and Objectives Newborns delivered late-preterm (between 340/7 and 366/7 weeks of gestation) are at increased risk of respiratory distress syndrome (RDS). Polymorphisms within the surfactant protein (SP) A and B gene have been shown to predispose to RDS in preterm neonates. The aim of this study was to investigate whether specific SP-A and/or SP-B genetic variants are also associated with RDS in infants born late-preterm. Methods This prospective cross-sectional study included 56 late-preterm infants with and 60 without RDS. Specific SP-A1/SP-A2 haplotypes and SP-B Ile131Thr polymorphic alleles were determined in blood specimens using polymerase-chain-reaction and DNA sequencing. Results The SP-A1 6A4 and the SP-A2 1A5 haplotypes were significantly overrepresented in newborns with RDS compared to controls (OR 2.86, 95%CI 1.20–6.83 and OR 4.68, 95%CI 1.28–17.1, respectively). The distribution of the SP-B Ile131Thr genotypes was similar between the two late-preterm groups. Overall, the SP-A1 6A4 or/and SP-A2 1A5 haplotype was present in 20 newborns with RDS (35.7%), resulting in a 4.2-fold (1.60–11.0) higher probability of RDS in carriers. Multivariable regression analysis revealed that the effect of SP-A1 6A4 and SP-A2 1A5 haplotypes was preserved when adjusting for known risk or protective factors, such as male gender, smaller gestational age, smaller weight, complications of pregnancy, and administration of antenatal corticosteroids. Conclusions Specific SP-A genetic variants may influence the susceptibility to RDS in late-preterm infants, independently of the effect of other perinatal factors. PMID:27835691

  3. Dickkopf proteins influence lung epithelial cell proliferation in idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Pfaff, E-M; Becker, S; Günther, A; Königshoff, M

    2011-01-01

    Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with unknown pathogenesis. The WNT/β-catenin pathway has recently been reported to be operative in epithelial cells in IPF. Dickkopf (DKK) proteins are known to regulate WNT signalling via interaction with Kremen (KRM) receptors, yet their expression and role in the adult lung and in IPF has not been addressed. We analysed the expression, localisation and function of DKK and KRM proteins in IPF lungs using Western blotting, quantitative RT-PCR, immunohistochemistry, ELISA and functional in vitro studies. Enhanced expression of DKK1 and DKK4 and KRM1 was detected in lung homogenates of IPF patients compared with transplant donors. Immunohistochemistry revealed that DKK1 was predominantly localised in basal bronchial epithelial cells. Furthermore, prominent expression of all proteins was observed in hyperplastic alveolar epithelial cells in IPF. Quantitative measurement of DKK1 revealed enhanced protein expression in the bronchoalveolar lumen of IPF patients. Finally, functional studies using human bronchial and alveolar epithelial cell lines demonstrated that WNT-induced epithelial cell proliferation is regulated by DKK1 in a dose-dependent fashion. In summary, DKK proteins are expressed in the lung epithelium in IPF. DKK proteins influence epithelial cell proliferation and may, therefore, be suitable therapeutic targets for IPF.

  4. Regulation of p53-mediated changes in the uPA-fibrinolytic system and in lung injury by loss of surfactant protein-C expression in alveolar epithelial cells.

    Science.gov (United States)

    Puthusseri, Bijesh; Marudamuthu, Amarnath S; Tiwari, Nivedita; Fu, Jian; Idell, Steven; Shetty, Sreerama

    2017-04-06

    Pulmonary surfactant protein-C (SP-C) expression by type II alveolar epithelial cells (AECs) is markedly reduced in diverse types of lung injuries and is often associated with AEC apoptosis. It is unclear whether loss of SP-C contributes to the increased p53 and urokinase-type plasminogen activator (uPA) system cross talk and apoptosis of AECs. We therefore inhibited SP-C expression in human and murine AECs using lentivirus vector expressing shRNA and tested p53 and downstream changes in uPA-fibrinolytic system. Inhibition of SP-C expression in AECs induced p53 and activated caspase-3, indicating AEC apoptosis. We also found that bleomycin or cigarette smoke exposure failed to inhibit SP-C expression or apoptosis in AECs in p53- and plasminogen activator inhibitor-1 (PAI-1)-deficient mice. Depletion of SP-C expression by lentiviral SP-C shRNA in PAI-1-deficient mice failed to induce p53 or apoptosis in AECs, while it increased both AEC p53 and apoptosis in wild type or uPA-deficient mice. SP-C inhibition in AECs also increased in CXCL1 and CXCL2, and their receptor CXCR2 as well as ICAM-1 expression, indicative of a pro-inflammatory response. Overexpression of p53-binding 3'UTR sequences in AECs inhibited PAI-1 induction while maintaining uPA and uPAR protein and mRNA expression. Further, caveolin-1 expression and phosphorylation were increased in AECs indicating an intricate link between caveolin-1 and Src kinase-mediated cell signalling and AEC apoptosis due to loss of SP-C expression through p53 and uPA system-mediated cross-talk. The role of uPA, PAI-1 and p53 in the regulation of AEC apoptosis after injury was also determined in knock out mice.

  5. The effect of interleukin-13 (IL-13 and interferon-γ (IFN-γ on expression of surfactant proteins in adult human alveolar type II cells in vitro

    Directory of Open Access Journals (Sweden)

    Mason Robert J

    2010-11-01

    Full Text Available Abstract Background Surfactant proteins are produced predominantly by alveolar type II (ATII cells, and the expression of these proteins can be altered by cytokines and growth factors. Th1/Th2 cytokine imbalance is suggested to be important in the pathogenesis of several adult lung diseases. Recently, we developed a culture system for maintaining differentiated adult human ATII cells. Therefore, we sought to determine the effects of IL-13 and IFN-γ on the expression of surfactant proteins in adult human ATII cells in vitro. Additional studies were done with rat ATII cells. Methods Adult human ATII cells were isolated from deidentified organ donors whose lungs were not suitable for transplantation and donated for medical research. The cells were cultured on a mixture of Matrigel and rat-tail collagen for 8 d with differentiation factors and human recombinant IL-13 or IFN-γ. Results IL-13 reduced the mRNA and protein levels of surfactant protein (SP-C, whereas IFN-γ increased the mRNA level of SP-C and proSP-C protein but not mature SP-C. Neither cytokine changed the mRNA level of SP-B but IFN-γ slightly decreased mature SP-B. IFN-γ reduced the level of the active form of cathepsin H. IL-13 also reduced the mRNA and protein levels of SP-D, whereas IFN-γ increased both mRNA and protein levels of SP-D. IL-13 did not alter SP-A, but IFN-γ slightly increased the mRNA levels of SP-A. Conclusions We demonstrated that IL-13 and IFN-γ altered the expression of surfactant proteins in human adult ATII cells in vitro. IL-13 decreased SP-C and SP-D in human ATII cells, whereas IFN-γ had the opposite effect. The protein levels of mature SP-B were decreased by IFN-γ treatment, likely due to the reduction in active form cathpesin H. Similarly, the active form of cathepsin H was relatively insufficient to fully process proSP-C as IFN-γ increased the mRNA levels for SP-C and proSP-C protein, but there was no increase in mature SP-C. These observations

  6. High postoperative serum levels of surfactant type B as novel prognostic markers for congenital heart surgery

    Directory of Open Access Journals (Sweden)

    Onur Is?k

    2014-04-01

    Full Text Available Objective: Congenital heart diseases are observed in 5 to 8 of every 1000 live births. The presence of a valuable biomarker during the surgical periods may aid the clinician in a more accurate prognosis during treatment. Methods: For this reason, surfactant protein B plasma levels may help to evaluate patients with cardiac problems diminishing the alveolocapillary membrane stability. In this study, plasma levels of this biomarker were measured in the preoperative and postoperative periods. This study was conducted to detect the differences between pulmonary hypertensive and normotensive patients. The differences before and after cardiopulmonary bypass were examined. Results: The differences in cardiopulmonary bypass time, cross-clamp time , inotropic support dose, and duration of intensive care of patients with and without pulmonary hypertensive were found to be statistically significant (P<0.05. The results revealed that this pathophysiological state was related to other variables that were studied. We believe that the differences in preoperative and postoperative SPB levels could be attributed to alveolocapillary membrane damage and alveolar surfactant dysfunction. We found that this pathophysiological condition was significantly associated with postoperative parameters. Conclusion: The findings of the current study showed that surfactant protein B was present in the blood of patients with a congenital heart disease during the preoperative period. Long by-pass times may exert damage to the alveolocapillary membrane in patients with pulmonary hypertension and preoperative heart failure, and it is recommended to keep the option of surfactant therapy in mind during the postoperative course at the intensive care unit before preparing the patients for extubation.

  7. Dispersion of single-walled carbon nanotubes by a natural lung surfactant for pulmonary in vitro and in vivo toxicity studies

    Directory of Open Access Journals (Sweden)

    Mercer Robert R

    2010-10-01

    Full Text Available Abstract Background Accumulating evidence indicate that the degree of dispersion of nanoparticles has a strong influence on their biological activities. The aims of this study were to develop a simple and rapid method of nanoparticle dispersion using a natural lung surfactant and to evaluate the effect of dispersion status of SWCNT on cytotoxicity and fibrogenicity in vitro and in vivo. Results The natural lung surfactant Survanta® was used to disperse single-walled carbon nanotubes (SWCNT in a biological medium. At physiologically relevant concentrations, Survanta® produced well dispersed SWCNT without causing a cytotoxic or fibrogenic effect. In vitro studies show that Survanta®-dispersed SWCNT (SD-SWCNT stimulated proliferation of lung epithelial cells at low doses (0.04-0.12 μg/ml or 0.02-0.06 μg/cm2 exposed surface area but had a suppressive effect at high doses. Non-dispersed SWCNT (ND-SWCNT did not exhibit these effects, suggesting the importance of dispersion status of SWCNT on bioactivities. Studies using cultured human lung fibroblasts show that SD-SWCNT stimulated collagen production of the cells. This result is supported by a similar observation using Acetone/sonication dispersed SWCNT (AD-SWCNT, suggesting that Survanta® did not mask the bioactivity of SWCNT. Likewise, in vivo studies show that both SD-SWCNT and AD-SWCNT induced lung fibrosis in mice, whereas the dispersing agent Survanta® alone or Survanta®-dispersed control ultrafine carbon black had no effect. Conclusions The results indicate that Survanta® was effective in dispersing SWCNT in biological media without causing cytotoxic effects at the test concentrations used in this study. SD-SWCNT stimulated collagen production of lung fibroblasts in vitro and induced lung fibrosis in vivo. Similar results were observed with AD-SWCNT, supporting the conclusion that Survanta® did not mask the bioactivities of SWCNT and thus can be used as an effective dispersing agent

  8. Maternal Baicalin Treatment Increases Fetal Lung Surfactant Phospholipids in Rats

    Directory of Open Access Journals (Sweden)

    Chung-Ming Chen

    2011-01-01

    Full Text Available Baicalin is a flavonoid compound purified from the medicinal plant Scutellaria baicalensis Georgi and has been reported to stimulate surfactant protein (SP-A gene expression in human lung epithelial cell lines (H441. The aims of this study were to determine whether maternal baicalin treatment could increase lung surfactant production and induce lung maturation in fetal rats. This study was performed with timed pregnant Sprague-Dawley rats. One-day baicalin group mothers were injected intraperitoneally with baicalin (5 mg/kg/day on Day 18 of gestation. Two-day baicalin group mothers were injected intraperitoneally with baicalin (5 mg/kg/day on Days 17 and 18 of gestation. Control group mothers were injected with vehicle alone on Day 18 of gestation. On Day 19 of gestation, fetuses were delivered by cesarean section. Maternal treatment with 2-day baicalin significantly increased saturated phospholipid when compared with control group and total phospholipid in fetal lung tissue when compared with control and 1-day baicalin groups. Antenatal treatment with 2-day baicalin significantly increased maternal growth hormone when compared with control group. Fetal lung SP-A mRNA expression and maternal serum corticosterone levels were comparable among the three experimental groups. Maternal baicalin treatment increases pulmonary surfactant phospholipids of fetal rat lungs and the improvement was associated with increased maternal serum growth hormone. These results suggest that antenatal baicalin treatment might accelerate fetal rat lung maturation.

  9. Reexpansion pulmonary edema

    OpenAIRE

    Genofre Eduardo Henrique; Vargas Francisco S.; Teixeira Lisete R.; Vaz Marcelo Alexandre Costa; Marchi Evaldo

    2003-01-01

    Reexpansion pulmonary edema (RPE) is a rare, but frequently lethal, clinical condition. The precise pathophysiologic abnormalities associated with this disorder are still unknown, though decreased pulmonary surfactant levels and a pro-inflammatory status are putative mechanisms. Early diagnosis is crucial, since prognosis depends on early recognition and prompt treatment. Considering the high mortality rates related to RPE, preventive measures are still the best available strategy for patient...

  10. Protective Effects of Surfactant Protein D (SP-D) Treatment in 1,3-β-glucan-modulated Allergic Inflammation

    DEFF Research Database (Denmark)

    Fakih, Dalia; Pilecki, Bartosz; Schlosser, Anders;

    2015-01-01

    SP-D treatment. 1,3-β-glucan-treatment did, however, induce pulmonary neutrophilic infiltration and increased TNF-α levels in BAL, independently of OVA-induced allergy. This infiltration was also reversed by treatment with rfhSP-D. 1,3-β-glucan reduced OVA-induced mucous cell metaplasia, Th2 cytokines and IFN......-γ production. rfhSP-D treatment further reduced mucous metaplasia and Th2 cytokine secretion to background levels. In summary, rfhSP-D treatment resulted in attenuation of both allergic inflammation and 1,3-β-glucan mediated neutrophilic inflammation. Our data suggest that treatment with high dose SP......SP-D is a pulmonary collectin important in lung immunity. SP-D-deficient mice (Sftpd(-/-)) are reported to be susceptible to ovalbumin (OVA)- and fungal allergen-induced pulmonary inflammation, while treatment with exogenous SP-D has therapeutic effects in such disease models. β...

  11. Casein protein results in higher prandial and exercise induced whole body protein anabolism than whey protein in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Engelen, Mariëlle P K J; Rutten, Erica P A; De Castro, Carmen L N; Wouters, Emiel F M; Schols, Annemie M W J; Deutz, Nicolaas E P

    2012-09-01

    Exercise is known to improve physical functioning and health status in Chronic Obstructive Pulmonary Disease (COPD). Recently, disturbances in protein turnover and amino acid kinetics have been observed after exercise in COPD. The objective was to investigate which dairy protein is able to positively influence the protein metabolic response to exercise in COPD. 8 COPD patients and 8 healthy subjects performed a cycle test on two days while ingesting casein or whey protein. Whole body protein breakdown (WbPB), synthesis (WbPS), splanchnic amino acid extraction (SPE), and NetWbPS (=WbPS-WbPB) were measured using stable isotope methodology during 20 min of exercise (at 50% peak work load of COPD group). The controls performed a second exercise test at the same relative workload. Exercise was followed by 1 h of recovery. In the healthy group, WbPS, SPE, and NetPS were higher during casein than during whey feeding (Pexercise, independent of exercise intensity (PCOPD due to lower WbPB (Pexercise during casein and whey feeding in COPD (Pexercise were higher in COPD (Pexercise, lower NetPS values were found independent of protein type in both groups. Casein resulted in more protein anabolism than whey protein which was maintained during and following exercise in COPD. Optimizing protein intake might be of importance for muscle maintenance during daily physical activities in COPD.

  12. Synthetic lung surfactants containing SP-B and SP-C peptides plus novel phospholipase-resistant lipids or glycerophospholipids

    Directory of Open Access Journals (Sweden)

    Robert H. Notter

    2016-10-01

    Full Text Available Background This study examines the biophysical and preclinical pulmonary activity of synthetic lung surfactants containing novel phospholipase-resistant phosphonolipids or synthetic glycerophospholipids combined with Super Mini-B (S-MB DATK and/or SP-Css ion-lock 1 peptides that replicate the functional biophysics of surfactant proteins (SP-B and SP-C. Phospholipase-resistant phosphonolipids used in synthetic surfactants are DEPN-8 and PG-1, molecular analogs of dipalmitoyl phosphatidylcholine (DPPC and palmitoyl-oleoyl phosphatidylglycerol (POPG, while glycerophospholipids used are active lipid components of native surfactant (DPPC:POPC:POPG 5:3:2 by weight. The objective of the work is to test whether these novel lipid/peptide synthetic surfactants have favorable preclinical activity (biophysical, pulmonary for therapeutic use in reversing surfactant deficiency or dysfunction in lung disease or injury. Methods Surface activity of synthetic lipid/peptide surfactants was assessed in vitro at 37 °C by measuring adsorption in a stirred subphase apparatus and dynamic surface tension lowering in pulsating and captive bubble surfactometers. Shear viscosity was measured as a function of shear rate on a Wells-Brookfield micro-viscometer. In vivo pulmonary activity was determined by measuring lung function (arterial oxygenation, dynamic lung compliance in ventilated rats and rabbits with surfactant deficiency/dysfunction induced by saline lavage to lower arterial PO2 to <100 mmHg, consistent with clinical acute respiratory distress syndrome (ARDS. Results Synthetic surfactants containing 5:3:2 DPPC:POPC:POPG or 9:1 DEPN-8:PG-1 combined with 3% (by wt of S-MB DATK, 3% SP-Css ion-lock 1, or 1.5% each of both peptides all adsorbed rapidly to low equilibrium surface tensions and also reduced surface tension to ≤1 mN/m under dynamic compression at 37 °C. However, dual-peptide surfactants containing 1.5% S-MB DATK + 1.5% SP-Css ion-lock 1 combined with

  13. The correlation of vitamin D level and vitamin D-binding protein gene polymorphism in chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    李晓晨

    2014-01-01

    Objective To assess the correlation of serum 25-hydroxyvitamin D(25-OHD)levels with vitamin D-binding protein(the group-specific component,GC)gene polymorphism in chronic obstructive pulmonary disease(COPD).Methods In a cross-sectional case-control study,250 participants,including 116 COPD patients with smoking history and 134 healthy smokers,were in-

  14. Analysis of proteins in bronchoalveolar lavage fluids during pulmonary edema resulting from nitrogen dioxide and cadmium exposure

    Energy Technology Data Exchange (ETDEWEB)

    Gurley, L.R.; London, J.E.; Dethloff, L.A.; Lehnert, B.E.

    1988-01-01

    We have developed a new HPLC method by which quantitative measurements can be made on the biochemical constituents of the extracellular fluid lining of the lung as sampled by bronchoalveolar lavage. Nine of the fractions are proteins, two are phospholipids, and two fractions remained unidentified. Rats were subjected to the intrapulmonary deposition of cadmium, a treatment model known to induce pulmonary edema and cause a translocation of blood compartment proteins into the lung's alveolar space compartment. Resulting pulmonary edema was hallmarked by /approximately/25-fold increases in three major blood compartment-derived HPLC protein fractions, two of which have been identified as albumin and immunoglobulin(s). Analysis of lavage fluid from rats exposed to 100 ppM NO/sub 2/ for 15 min, an exposure regimen which also produces pulmonary edema, indicated that the three blood compartment proteins in the lavage fluids were elevated 35- to 72-fold over controls 24 h after exposure. These results demonstrate that HPLC can be used to provide a highly sensitive method for detection and quantitation of pulmonary edema that can occur in acute lung injuries resulting from environmental insults.

  15. C reactive protein and chronic obstructive pulmonary disease: a Mendelian randomisation approach

    DEFF Research Database (Denmark)

    Vestbo, Jørgen; Lange, Peter; Nordestgaard, Børge G

    2011-01-01

    Background It is unclear whether elevated plasma C reactive protein (CRP) is causally related to chronic obstructive pulmonary disease (COPD). The authors tested the hypothesis that genetically elevated plasma CRP causes COPD using a Mendelian randomisation design. Methods The authors measured high......-sensitivity CRP in plasma, genotyped for four single nucleotide polymorphisms in the CRP gene, and screened for spirometry-defined COPD and hospitalisation due to COPD in 7974 individuals from the Copenhagen City Heart Study and in 32¿652 individuals from the Copenhagen General Population Study. Results Elevated...... plasma CRP >3 mg/l compared with City Heart Study and the Copenhagen General Population Study, respectively. Genotype combinations...

  16. Effect of surfactant replacement on Pneumocystis carinii pneumonia in rats

    NARCIS (Netherlands)

    E.P. Eijking (Eric); G.J. van Daal; R. Tenbrinck (Robert); A. Luijendijk (Ad); J.F. Sluiters (Hans); E. Hannappel (E.); B.F. Lachmann (Burkhard)

    1991-01-01

    textabstractThe effect of intratracheal surfactant instillation on pulmonary function in rats with Pneumocystis carinii pneumonia (PCP) was investigated. In those animals which developed PCP with severe respiratory failure after administration of cortisone acetate s. c. over 8-12 weeks, pulmonary fu

  17. Absorption-enhancing effects of gemini surfactant on the intestinal absorption of poorly absorbed hydrophilic drugs including peptide and protein drugs in rats.

    Science.gov (United States)

    Alama, Tammam; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2016-02-29

    In general, the intestinal absorption of small hydrophilic molecules and macromolecules like peptides, after oral administration is very poor. Absorption enhancers are considered to be one of the most promising agents to enhance the intestinal absorption of drugs. In this research, we focused on a gemini surfactant, a new type of absorption enhancer. The intestinal absorption of drugs, with or without sodium dilauramidoglutamide lysine (SLG-30), a gemini surfactant, was examined by an in situ closed-loop method in rats. The intestinal absorption of 5(6)-carboxyfluorescein (CF) and fluorescein isothiocyanate-dextrans (FDs) was significantly enhanced in the presence of SLG-30, such effect being reversible. Furthermore, the calcium levels in the plasma significantly decreased when calcitonin was co-administered with SLG-30, suggestive of the increased intestinal absorption of calcitonin. In addition, no significant increase in the of lactate dehydrogenase (LDH) activity or in protein release from the intestinal epithelium was observed in the presence of SLG-30, suggestive of the safety of this compound. These findings indicate that SLG-30 is an effective absorption-enhancer for improving the intestinal absorption of poorly absorbed drugs, without causing serious damage to the intestinal epithelium.

  18. Prediction markers for respiratory distress syndrome: evaluation of the stable microbubble test, surfactant protein-A and hepatocyte growth factor levels in amniotic fluid.

    Directory of Open Access Journals (Sweden)

    Kumazawa K

    2003-02-01

    Full Text Available Surfactant treatment in infants with respiratory distress syndrome (RDS has decreased neonatal mortality. With the advent of this therapy, it has become important to predict accurately the fetal lung maturity of a fetus before delivery. We evaluated the stable microbubble test (SMT, surfactant protein-A (SP-A and hepatocyte growth factor (HGF in amniotic fluid as predicting markers for RDS. Of 55 amniotic fluid samples obtained by amniocentesis from women less than 37 weeks pregnant, the SMT values were as follows: sensitivity 76.5%, specificity 84.2%, positive predictive value 68.4%, negative predictive value 88.9% and overall accuracy 81.8%. For SP-A, the values were 88.2%, 65.8%, 53.6%, 92.6% and 72.7%, respectively. If we used both SMT and SP-A, we could diagnose with 100% accuracy that a case with measurements of SMT > or = 2 and SP-A > or = 420 ng/ml would not complicate with RDS (24/24. However, the RDS diagnostic accuracy of HGF does not equal to those of SMT and SP-A levels. We concluded that the rapidity, simplicity and reliability of SMT was very useful during 24-36 weeks of gestation as a bedside procedure to predict fetuses likely to develop RDS. We also noted the additive effect of SP-A in improving the accuracy of lung maturity diagnosis.

  19. Effect of acute food restriction on pulmonary growth and protein turnover in preterm guinea pigs.

    Science.gov (United States)

    Kelly, F J; Fussell, J C; Postle, T D

    1992-02-01

    The effects of food restriction on the growth and protein turnover of the immature lung were investigated. Preterm guinea pigs, delivered by cesarean section at 65 days gestation (term = 68 days), were given free access to a lactating dam or restricted from feeding for 48 h. Food restriction resulted in significantly reduced body and lung (P less than 0.05) weight compared with fed controls. The rate of pulmonary protein synthesis determined in vivo was reduced by 33% in the food-restricted pups (28.9 +/- 10.2 vs. 19.4 +/- 4.5%, P less than 0.05 for control and food-restricted pups, respectively), whereas the calculated rate of protein breakdown remained unchanged. The inhibition of protein synthesis was accounted for by a 36% decrease in ribosomal efficiency (11.03 +/- 2.61 vs. 7.04 +/- 1.26%, P less than 0.01 for control and food-restricted pups, respectively), whereas ribosomal capacity was unaltered. Polyribosomal analysis indicated an increase in the proportion of RNA present in polysomes and a fall in the free monomer pool (26%), suggesting that food restriction blocked translation by reducing the rate of peptide chain elongation. This finding was confirmed by the analysis of ribosome transit times, which indicated a significant increase in the elongation rate in the lungs from food-restricted pups (0.51 +/- 0.11 vs. 0.94 +/- 0.19 min, P less than 0.05 for control and food-restricted pups, respectively). These results imply that nutrient supply plays an important role in protein deposition and hence growth and repair capacity of the immature lung.

  20. Familial Interstitial Pulmonary Fibrosis: A Large Family with Atypical Clinical Features

    Directory of Open Access Journals (Sweden)

    Ranji Chibbar

    2010-01-01

    Full Text Available A large kindred of familial pulmonary fibrosis is reported. Six members from the first two generations of this particular kindred were described more than 40 years previously; six more individuals from the third and fourth generations have also been evaluated. The proband, now 23 years of age, has mild disease; the other 11 documented affected family members all died from their disease at an average age of 37 years (range 25 to 50 years. The pathology was that of usual interstitial pneumonia, as is typical in idiopathic pulmonary fibrosis. However, the initial radiographic pattern in many of these individuals was upper lobe and nodular and, along with the young age, was atypical for idiopathic pulmonary fibrosis. Several genetic abnormalities have been associated with familial pulmonary fibrosis. The present study examined the genes coding for surfactant protein-C, ATP-binding cassette protein A3 and telomerase, and found no abnormalities.

  1. Exploration of twisted intramolecular charge transfer fluorescence properties of trans-2-[4-(dimethylamino)styryl]benzothiazole to characterize the protein-surfactant aggregates

    Energy Technology Data Exchange (ETDEWEB)

    Muthusubramanian, Sowmiya [Department of Chemistry, Birla Institute of Technology and Science, Pilani 333031, Rajasthan (India); Saha, Subit Kumar, E-mail: sksaha@bits-pilani.ac.in [Department of Chemistry, Birla Institute of Technology and Science, Pilani 333031, Rajasthan (India)

    2012-08-15

    The characterization of aggregates of an anionic surfactant, sodium dodecyl sulphate (SDS) with bovine serum albumin (BSA) in various regions of binding isotherm of SDS to BSA with increasing concentration of the former have been done by exploring the twisted intramolecular charge transfer (TICT) fluorescence properties of a probe, trans-2-[4-(dimethylamino)styryl] benzothiazole (DMASBT). The TICT fluorescence, steady-state fluorescence anisotropy and time-resolved fluorescence of DMASBT, and the fluorescence resonance energy transfer (FRET) study reveal the characteristics of the native protein as well as the protein-surfactant aggregates viz., micropolarity, microviscosity, locations of probe, denaturation of protein in various regions of binding isotherm, and also the validation of necklace-bead model. The changes in the polarity and the viscosity of the microenvironment around the probe from one binding region of SDS to other have been reflected in the highly sensitive fluorescence properties of DMASBT. The study of FRET between the DMASBT and the tryptophan residue (Trp) of BSA has identified the locations of the probe molecule in the native protein as well as that in various BSA-SDS aggregates. The energy transfer efficiency decreases, whereas the distance between the DMASBT and the Trp residue increases with increasing concentration of SDS. The significant change in the conformations of protein molecules during the non-cooperative binding region of SDS is evidenced by the fluorescence anisotropic behavior of DMASBT in the same region. - Highlights: Black-Right-Pointing-Pointer Micropolarity and microviscosity of environment around the probe in BSA-SDS aggregates is reported. Black-Right-Pointing-Pointer Denaturation of protein is demonstrated by the TCSPC of DMASBT and FRET study. Black-Right-Pointing-Pointer Location of the probe in the native protein and BSA-SDS aggregates is identified using FRET study. Black-Right-Pointing-Pointer During unfolding of BSA

  2. Acute chlorine gas exposure produces transient inflammation and a progressive alteration in surfactant composition with accompanying mechanical dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Massa, Christopher B.; Scott, Pamela; Abramova, Elena; Gardner, Carol; Laskin, Debra L.; Gow, Andrew J., E-mail: Gow@rci.rutgers.edu

    2014-07-01

    Acute Cl{sub 2} exposure following industrial accidents or military/terrorist activity causes pulmonary injury and severe acute respiratory distress. Prior studies suggest that antioxidant depletion is important in producing dysfunction, however a pathophysiologic mechanism has not been elucidated. We propose that acute Cl{sub 2} inhalation leads to oxidative modification of lung lining fluid, producing surfactant inactivation, inflammation and mechanical respiratory dysfunction at the organ level. C57BL/6J mice underwent whole-body exposure to an effective 60 ppm-hour Cl{sub 2} dose, and were euthanized 3, 24 and 48 h later. Whereas pulmonary architecture and endothelial barrier function were preserved, transient neutrophilia, peaking at 24 h, was noted. Increased expression of ARG1, CCL2, RETLNA, IL-1b, and PTGS2 genes was observed in bronchoalveolar lavage (BAL) cells with peak change in all genes at 24 h. Cl{sub 2} exposure had no effect on NOS2 mRNA or iNOS protein expression, nor on BAL NO{sub 3}{sup −} or NO{sub 2}{sup −}. Expression of the alternative macrophage activation markers, Relm-α and mannose receptor was increased in alveolar macrophages and pulmonary epithelium. Capillary surfactometry demonstrated impaired surfactant function, and altered BAL phospholipid and surfactant protein content following exposure. Organ level respiratory function was assessed by forced oscillation technique at 5 end expiratory pressures. Cl{sub 2} exposure had no significant effect on either airway or tissue resistance. Pulmonary elastance was elevated with time following exposure and demonstrated PEEP refractory derecruitment at 48 h, despite waning inflammation. These data support a role for surfactant inactivation as a physiologic mechanism underlying respiratory dysfunction following Cl{sub 2} inhalation. - Highlights: • Effect of 60 ppm*hr Cl{sub 2} gas on lung inflammation and mechanical function examined. • Pulmonary inflammation is transient and minor.

  3. The role of exogenous surfactant in the treatment of ARDS%外源性肺表面活性物质在ARDS中的治疗作用

    Institute of Scientific and Technical Information of China (English)

    陆月明

    2004-01-01

    Several studies have demonstrated that alterations of pulmonary surfactant system contribute to the lung dysfunction associated with acute respiratory distress syndrome (ARDS). There have been many animal experiments and clinical investigations evaluating exogenous surfactant in ARDS models or patients. Exogenous surfactant administration has proven inconsistent as a therapeutic modality for patients with ARDS. Various factors that may influence a host response to exogenous surfactant, these factots include: the nature and severity of the underlying injury,the surfactant preparation utilized, the amount, frequency, and method of surfactant administration, the mode of ventilation used during and after surfactant delivery, and the timing or surfactant administration over the course of the illness

  4. Induction of systemic and mucosal immunity and maintenance of its memory against influenza A virus by nasal vaccination using a new mucosal adjuvant SF-10 derived from pulmonary surfactant in young cynomolgus monkeys.

    Science.gov (United States)

    Mizuno, Dai; Kimoto, Takashi; Sakai, Satoko; Takahashi, Etsuhisa; Kim, Hyejin; Kido, Hiroshi

    2016-04-07

    Induction of systemic and mucosal immunity and maintenance of its memory was investigated in 12 young male cynomolgus monkeys after intranasal instillation of flu vaccine using a new mucosal adjuvant SF-10 derived from pulmonary surfactant constituents. Split-product of influenza virus A/California/7/2009(H1N1)pdm hemagglutinin vaccine (HAv) at 15 μg with or without SF-10 and the adjuvant alone were instilled intranasally three times every 2 weeks. SF-10-adjuvanted HAv (SF-10-HAv) elicited significantly higher HAv-specific IgG and hemagglutinin inhibition (HI) titers in serum and HAv-specific secretory IgA and its neutralizing activities in nasal washes compared with HAv antigen and SF-10 alone. Significant cross-neutralizing activities of nasal washes after the third vaccination to several other H1N1 and H3N2 strains were observed. HI titers in serum and neutralizing activities in nasal washes reached peak levels at 6 weeks after initial vaccination, then gradually decreased after 10 weeks and returned to the baseline levels at 36 weeks. A single intranasal revaccination of SF-10-HAv at 36 weeks rapidly and significantly increased both immunity in serum and nasal washes compared with naïve monkeys. Revaccination by one or two doses achieved almost maximal immunity at 2 or 4 weeks after instillation. Statistically significant adverse effects (e.g., body weight loss, elevated body temperature, nasal discharge, change in peripheral blood leukocyte and platelet counts) were not observed for 2 weeks after vaccination of SF-10-HAv, HAv or SF-10 and also during the experimental period. These results in young monkey model suggest the potential of clinical use SF-10 for intranasal flu vaccine.

  5. Interfacial mechanisms for stability of surfactant-laden films

    CERN Document Server

    Bhamla, M Saad; Alvarez-Valenzuela, Marco A; Tajuelo, Javier; Fuller, Gerald G

    2016-01-01

    Thin liquid films are central to everyday life. They are ubiquitous in modern technology (pharmaceuticals, coatings), consumer products (foams, emulsions) and also serve vital biological functions (tear film of the eye, pulmonary surfactants in the lung). A common feature in all these examples is the presence of surface-active molecules at the air-liquid interface. Though they form only molecularly-thin layers, these surfactants produce complex surface stresses on the free surface, which have important consequences for the dynamics and stability of the underlying thin liquid film. Here we conduct simple thinning experiments to explore the fundamental mechanisms that allow the surfactant molecules to slow the gravity-driven drainage of the underlying film. We present a simple model that works for both soluble and insoluble surfactant systems. We show that surfactants with finite surface rheology influence bulk flow through viscoelastic interfacial stresses, while surfactants with inviscid surfaces achieve stab...

  6. [Effect of amygdalin on serum proteinic biomarker in pulmonary fibrosis of bleomycin-induced rat].

    Science.gov (United States)

    Du, Hai-Ke; Song, Fu-Cheng; Zhou, Xin; Li, He; Zhang, Jian-Peng

    2010-04-01

    To evaluate effect of amygdalin on expression of four biomarkers in the animal model of pulmonary fibrosis induced by bleomycin. Rats were given one dose (5 mg/kg) of bleomycin in bleomycin-treated groups, amygdalin-treated groups and saline in controls by intratracheal instillation exposed surgically. The amygdalin-treated groups rats were treated with intraperitoneal injection of amygdalin (15 mg x kg(-1) x day(-1)). The rats were sacrificed 7, 14 and 28 days after bleomycin administration. Polarized light microscopy and Image-Pro Plus detected I and III collagen expressed in Paraffin-embedded lung sections stained with Sirius red. Surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF MS) with weak cationic proteinchip (CM10) detected differentially expressed proteins in the pooled serum samples of all groups. Consistent fibrotic responses were found in all bleomycin and amygdalin-tread groups. On the 7th, 14th and 28th day after bleomycin or saline instillation, four differentially expressed proteins were detected in the pooled serum of all groups rats, consisting of 4 proteins with mass/charge ratio of 3530.7, 7043.5, 8332.6 and 9068.0, respectively. Compared with control groups, protein peaks intensity ratio with mass/charge ratio of 3530.7 on 7, 28 d and 7043.5, 8332.6 and 9068.0 on 7, 14 and 28 d was > 2 in bleomycin-treated groups. Compared with amygdalin-treated groups, protein peaks intensity with mass/charge ratio of 3530.7 at 7, 14, 28 d had no change almost, but protein peaks intensity ratio with mass/charge ratio of 7043.5 at 7 d, 8332.6 on 28 d and 9068.0 on 14 d was > 2 in bleomycin-tread groups. All the four protein peaks intensity had no change almost at other point. Amygdalin may reduce the bleomycin-induced increase of differentially expressed protein peak intensities in rat serum.

  7. Association between C-Reactive Protein and Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Sulhattin Arslan

    2013-03-01

    Full Text Available     Aim: In this study, we aimed to find out if there is an increase in the C-reactive protein (CRP levels in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD and in stable COPD (SCOPD andto determine the correlation of a possible increase with other markers of inflammation. Material and Method: All patients with AECOPD were also categorized according to radiologic findings. Chest X-rays were evaluated and COPD patients who had new infiltrates, consolidation, air bronkogram were considered to have pneumonia (PCOPD. SCOPD patients without a history of exacerbation for the previous 2 months were recruited prospectively from our outpatient clinic. The pulmonary function test results and the values of arterial blood gas analyses, leukocytes, neutrophils, and CRP measured within 24 hour of admission were obtained from the records of the patients with COPD,. Results: The mean serum CRP level during AECOPD was significantly higher compared to those in the control group and SCOPD patients. The mean CRP level was higher in the SCOPD patients compared to the control group as well. The serum CRP levels were positively correlated with the PaCO2 levels that showed the severity of the attack and negatively correlated with the pH, FEV1 and FEV1/FVC values. Positive correlation between leukocyte count and CRP was detected in all groups except the control group. Discussion:We indicated that there was an association between serum CRP levels and severity of COPD. In COPD exacerbations, leukocyte count and serum CRP levels had a significant positive correlation.

  8. Surfactant proteins SP-B and SP-C and their precursors in bronchoalveolar lavages from children with acute and chronic inflammatory airway disease

    Directory of Open Access Journals (Sweden)

    Winter Tobias

    2008-04-01

    Full Text Available Abstract Background The surfactant proteins B (SP-B and C (SP-C are important for the stability and function of the alveolar surfactant film. Their involvement and down-regulation in inflammatory processes has recently been proposed, but their level during neutrophilic human airway diseases are not yet known. Methods We used 1D-electrophoresis and Western blotting to determine the concentrations and molecular forms of SP-B and SP-C in bronchoalveolar lavage (BAL fluid of children with different inflammatory airway diseases. 21 children with cystic fibrosis, 15 with chronic bronchitis and 14 with pneumonia were included and compared to 14 healthy control children. Results SP-B was detected in BAL of all 64 patients, whereas SP-C was found in BAL of all but 3 children; those three BAL fluids had more than 80% neutrophils, and in two patients, who were re-lavaged later, SP-C was then present and the neutrophil count was lower. SP-B was mainly present as a dimer, SP-C as a monomer. For both qualitative and quantitative measures of SP-C and SP-B, no significant differences were observed between the four evaluated patient groups. Conclusion Concentration or molecular form of SP-B and SP-C is not altered in BAL of children with different acute and chronic inflammatory lung diseases. We conclude that there is no down-regulation of SP-B and SP-C at the protein level in inflammatory processes of neutrophilic airway disease.

  9. Current status and recognition of pulmonary surfactant for the treatment of acute respiratory distress syndrome%急性呼吸窘迫综合征的肺表面活性物质治疗现状和再认识

    Institute of Scientific and Technical Information of China (English)

    刘成军; 杜语慧

    2016-01-01

    Exogenous surfactant replacement has been successfully achieved and become standard therapy in neonatal respiratory distress syndrome,but clinical trials in acute respiratory distress syndrome (ARDS) had mixed results.Early studies show that pulmonary surfactant(PS) administration in ARDS can significantly improve oxygenation and decrease mortality,but in recent years,some clinical trials haven't achieve the most substantial benefits to long-term patient outcomes.The inconsistent results of clinical trials may have related to aspects of drug composition,dosing,delivery,and timing.At this time,surfactant therapy cannot be recommended as routine therapy in pediatric ARDS.%外源性肺表面活性物质(pulmonary surfactant,PS)替代治疗在新生儿呼吸窘迫综合征中的应用已经普及,且疗效确定,但是治疗小儿急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)的临床观察结果并不一致.早期研究发现PS可改善ARDS患儿的氧合,降低病死率,但近年来的研究显示PS并不能改善ARDS患儿的远期预后.研究结果的不同可能与PS制剂、给药剂量、给药方法、给药时机等有关.目前不推荐在ARDS治疗中常规使用PS.

  10. SET9-Mediated Regulation of TGF-β Signaling Links Protein Methylation to Pulmonary Fibrosis

    Directory of Open Access Journals (Sweden)

    Maximilianos Elkouris

    2016-06-01

    Full Text Available TGF-β signaling regulates a variety of cellular processes, including proliferation, apoptosis, differentiation, immune responses, and fibrogenesis. Here, we describe a lysine methylation-mediated mechanism that controls the pro-fibrogenic activity of TGF-β. We find that the methyltransferase Set9 potentiates TGF-β signaling by targeting Smad7, an inhibitory downstream effector. Smad7 methylation promotes interaction with the E3 ligase Arkadia and, thus, ubiquitination-dependent degradation. Depletion or pharmacological inhibition of Set9 results in elevated Smad7 protein levels and inhibits TGF-β-dependent expression of genes encoding extracellular matrix components. The inhibitory effect of Set9 on TGF-β-mediated extracellular matrix production is further demonstrated in mouse models of pulmonary fibrosis. Lung fibrosis induced by bleomycin or Ad-TGF-β treatment was highly compromised in Set9-deficient mice. These results uncover a complex regulatory interplay among multiple Smad7 modifications and highlight the possibility that protein methyltransferases may represent promising therapeutic targets for treating lung fibrosis.

  11. Evaluation of circulating proteins and hemodynamics towards predicting mortality in children with pulmonary arterial hypertension.

    Directory of Open Access Journals (Sweden)

    Brandie D Wagner

    Full Text Available Although many predictors have been evaluated, a set of strong independent prognostic mortality indicators has not been established in children with pediatric pulmonary arterial hypertension (PAH. The aim of this study was to identify a combination of clinical and molecular predictors of survival in PAH.This single-center, retrospective cohort study was performed from children with PAH between 2001 and 2008 at Children's Hospital Colorado. Blood samples from 83 patients (median age of 8.3 years-old were obtained. We retrospectively analyzed 46 variables, which included 27 circulating proteins, 7 demographic variables and 12 hemodynamic and echocardiographic variables for establishing the best predictors of mortality. A data mining approach was utilized to evaluate predictor variables and to uncover complex data structures while performing variable selection in high dimensional problems.Thirteen children (16% died during follow-up (median; 3.1 years and survival rates from time of sample collection at 1 year, 3 years and 5 years were 95%, 85% and 79%, respectively. A subset of potentially informative predictors were identified, the top four are listed here in order of importance: Tissue inhibitors of metalloproteinases-1 (TIMP-1, apolipoprotein-AI, RV/LV diastolic dimension ratio and age at diagnosis. In univariate analysis, TIMP-1 and apolipoprotein-AI had significant association with survival time (hazard ratio [95% confidence interval]: 1.25 [1.03, 1.51] and 0.70 [0.54-0.90], respectively. Patients grouped by TIMP-1 and apolipoprotein-AI values had significantly different survival risks (p<0.01.Important predictors of mortality were identified from a large number of circulating proteins and clinical markers in this cohort. If confirmed in other populations, measurement of a subset of these predictors could aid in management of pediatric PAH by identifying patients at risk for death. These findings also further support a role for the clinical

  12. Hypoxia stimulates prostacyclin synthesis in newborn pulmonary artery endothelium by increasing cyclooxygenase-1 protein.

    Science.gov (United States)

    North, A J; Brannon, T S; Wells, L B; Campbell, W B; Shaul, P W

    1994-07-01

    In newborn lambs, pulmonary prostacyclin (PGI2) production increases acutely in response to low oxygen. We tested the hypothesis that decreased oxygenation directly stimulates PGI2 synthesis in arterial segments and cultured endothelial cells from newborn lamb intrapulmonary arteries. In segments studied at PO2 of 680 mm Hg, the synthesis of PGI2 exceeded prostaglandin E2 (PGE2) by 73%. Endothelium removal lowered PGI2 by 77% and PGE2 by 66%. At low oxygen tension (PO2, 40 mm Hg), PGI2 and PGE2 synthesis rose by 96% and 102%, respectively. Similarly, in endothelial cells studied at PO2 of 680 mm Hg, the synthesis of PGI2 exceeded PGE2 by 50%, and at low oxygen tension both PGI2 and PGE2 increased (89% and 64%, respectively). Endothelial cell PGI2 synthesis maximally stimulated by bradykinin, A23187, or arachidonic acid was also increased at low PO2 by 50%, 66%, and 48%, respectively. PGE2 synthesis was similarly altered, increasing by 33%, 37%, and 41%, respectively. In contrast, lowering oxygen had minimal effect on PGI2 and PGE2 synthesis with exogenous PGH2, which is the product of cyclooxygenase. Immunoblot analyses revealed that there was a 2.6-fold greater abundance of cyclooxygenase-1 protein at PO2 of 40 versus 680 mm Hg, and the increase at lower oxygen tension was inhibited by cycloheximide. The cyclooxygenase-2 isoform was not detected. Thus, attenuated oxygenation directly stimulates PGI2 and PGE2 synthesis in intrapulmonary arterial segments and endothelial cells from newborn lambs. This process is due to enhanced cyclooxygenase activity related to increased abundance of the cyclooxygenase-1 protein, and this effect may be due to increased synthesis of the enzyme protein.

  13. Impact of kidney function and urinary protein excretion on pulmonary function in Japanese patients with chronic kidney disease.

    Science.gov (United States)

    Nakade, Yusuke; Toyama, Tadashi; Furuichi, Kengo; Kitajima, Shinji; Ohkura, Noriyuki; Sagara, Akihiro; Shinozaki, Yasuyuki; Hara, Akinori; Kitagawa, Kiyoki; Shimizu, Miho; Iwata, Yasunori; Oe, Hiroyasu; Nagahara, Mikio; Horita, Hiroshi; Sakai, Yoshio; Kaneko, Shuichi; Wada, Takashi

    2014-10-01

    Although the cardiorenal relationship in chronic kidney disease has been investigated, information about the lung-kidney relationship is limited. Here, we investigated the impact of kidney function and urinary protein excretion on pulmonary dysfunction. The data from pulmonary function tests and kidney function (estimated glomerular filtration rate [eGFR] and urinary protein) between 1 April 2005 and 30 June 2010 were selected from our laboratory database. Data were classified into 4 categories according to eGFR and proteinuria. Category 1, eGFR ≥60 ml/min/1.73 m(2) and urinary protein protein protein ≥0.3 g/gCr; and category 4, eGFR protein ≥0.3 g/gCr. Pulmonary function data were evaluated according to these 4 categories. A total of 133 participants without major respiratory disease, abnormal computed tomography and smoking history were enrolled. Hemoglobin (Hb)-adjusted percentage carbon monoxide diffusing capacity (%DLCO) in category 4 (46.2 ± 7.5) and category 2 (63.6 ± 17.8) were significantly lower than in category 1 (75.8 ± 18.9) (P protein protein ≥0.3 g/gCr (R = 0.81, P function test markers (percentage (%) vital capacity, % forced expiratory volume in one second (FEV1), FEV1/forced vital capacity, % total lung capacity, and % residual volume) were not significantly different between categories. This study suggests that decreased eGFR is associated with decreased %DLCO in proteinuric patients.

  14. Thermally cleavable surfactants

    Science.gov (United States)

    McElhanon, James R.; Simmons, Blake A.; Zifer, Thomas; Jamison, Gregory M.; Loy, Douglas A.; Rahimian, Kamyar; Long, Timothy M.; Wheeler, David R.; Staiger, Chad L.

    2006-04-04

    Two new surfactant molecules are reported which contain thermally labile Diels-Alder adducts connecting the polar and non-polar sections of each molecule. The two surfactants possess identical non-polar dodecyl tail segments but exhibit different polar headgroups. The surfactants become soluble in water when anionic salts are formed through the deprotonation of the surfactant headgroups by the addition of potassium hydroxide. When either surfactant is exposed to temperature above about 60.degree. C., the retro Diels-Alder reaction occurs, yielding hydrophilic and hydrophobic fragments and the aqueous solutions of the surfactants subsequently exhibit loss of all surface-active behavior.

  15. Thermally cleavable surfactants

    Energy Technology Data Exchange (ETDEWEB)

    McElhanon, James R. (Manteca, CA); Simmons, Blake A. (San Francisco, CA); Zifer, Thomas (Manteca, CA); Jamison, Gregory M. (Albuquerque, NM); Loy, Douglas A. (Albuquerque, NM); Rahimian, Kamyar (Albuquerque, NM); Long, Timothy M. (Urbana, IL); Wheeler, David R. (Albuquerque, NM); Staiger, Chad L. (Albuquerque, NM)

    2009-09-29

    Two new surfactant molecules are reported which contain thermally labile Diels-Alder adducts connecting the polar and non-polar sections of each molecule. The two surfactants possess identical non-polar dodecyl tail segments but exhibit different polar headgroups. The surfactants become soluble in water when anionic salts are formed through the deprotonation of the surfactant headgroups by the addition of potassium hydroxide. When either surfactant is exposed to temperature above about 60.degree. C., the retro Diels-Alder reaction occurs, yielding hydrophilic and hydrophobic fragments or the aqueous solutions of the surfactants subsequently exhibit loss of all surface-active behavior.

  16. Thermally cleavable surfactants

    Energy Technology Data Exchange (ETDEWEB)

    McElhanon, James R. (Manteca, CA); Simmons, Blake A. (San Francisco, CA); Zifer, Thomas (Manteca, CA); Jamison, Gregory M. (Albuquerque, NM); Loy, Douglas A. (Albuquerque, NM); Rahimian, Kamyar (Albuquerque, NM); Long, Timothy M. (Urbana, IL); Wheeler, David R. (Albuquerque, NM); Staiger, Chad L. (Albuquerque, NM)

    2009-11-24

    Two new surfactant molecules are reported which contain thermally labile Diels-Alder adducts connecting the polar and non-polar sections of each molecule. The two surfactants possess identical non-polar dodecyl tail segments but exhibit different polar headgroups. The surfactants become soluble in water when anionic salts are formed through the deprotonation of the surfactant headgroups by the addition of potassium hydroxide. When either surfactant is exposed to temperature above about 60.degree. C., the retro Diels-Alder reaction occurs, yielding hydrophilic and hydrophobic fragments or the aqueous solutions of the surfactants subsequently exhibit loss of all surface-active behavior.

  17. Role of lung surfactant in respiratory disease: current knowledge in large animal medicine.

    Science.gov (United States)

    Christmann, U; Buechner-Maxwell, V A; Witonsky, S G; Hite, R D

    2009-01-01

    Lung surfactant is produced by type II alveolar cells as a mixture of phospholipids, surfactant proteins, and neutral lipids. Surfactant lowers alveolar surface tension and is crucial for the prevention of alveolar collapse. In addition, surfactant contributes to smaller airway patency and improves mucociliary clearance. Surfactant-specific proteins are part of the innate immune defense mechanisms of the lung. Lung surfactant alterations have been described in a number of respiratory diseases. Surfactant deficiency (quantitative deficit of surfactant) in premature animals causes neonatal respiratory distress syndrome. Surfactant dysfunction (qualitative changes in surfactant) has been implicated in the pathophysiology of acute respiratory distress syndrome and asthma. Analysis of surfactant from amniotic fluid allows assessment of fetal lung maturity (FLM) in the human fetus and exogenous surfactant replacement therapy is part of the standard care in premature human infants. In contrast to human medicine, use and success of FLM testing or surfactant replacement therapy remain limited in veterinary medicine. Lung surfactant has been studied in large animal models of human disease. However, only a few reports exist on lung surfactant alterations in naturally occurring respiratory disease in large animals. This article gives a general review on the role of lung surfactant in respiratory disease followed by an overview of our current knowledge on surfactant in large animal veterinary medicine.

  18. Recent advances in alveolar biology: Evolution and function of alveolar proteins

    NARCIS (Netherlands)

    Orgeig, S.; Hiemstra, P.S.; Veldhuizen, E.J.A.; Casals, C.; Clark, H.W.; Hackzu, A.; Knudsen, L.; Possmayer, F.

    2010-01-01

    This review is focused on the evolution and function of alveolar proteins. The lung faces physical and environmental challenges, due to changing pressures/volumes and foreign pathogens, respectively. The pulmonary surfactant system is integral in protecting the lung from these challenges via two gro

  19. C-reactive protein as a predictor of prognosis in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Dahl, Morten; Vestbo, Jørgen; Lange, Peter

    2007-01-01

    RATIONALE: Patients with chronic obstructive pulmonary disease (COPD) have an ongoing systemic inflammation, which can be assessed by measuring serum C-reactive protein (CRP). OBJECTIVE: To determine whether increased serum CRP in individuals with airway obstruction predicts future hospitalizatio......%, respectively, among those older than 70 yr with a tobacco consumption above 15 g/d and an FEV(1)% predicted of less than 50. CONCLUSIONS: CRP is a strong and independent predictor of future COPD outcomes in individuals with airway obstruction........ During follow-up, 185 (14%) individuals were hospitalized due to COPD and 83 (6%) died of COPD. Incidences of COPD hospitalization and COPD death were increased in individuals with baseline CRP > 3 mg/L versus tobacco...... consumption, and ischemic heart disease, the hazard ratios for hospitalization and death due to COPD were increased at 1.4 (95% confidence interval, 1.0-2.0) and 2.2 (1.2-3.9) in individuals with baseline CRP > 3 mg/L versus

  20. Plasma protein thiols: an early marker of oxidative stress in asthma and chronic obstructive pulmonary disease.

    Science.gov (United States)

    Zinellu, Angelo; Fois, Alessandro Giuseppe; Sotgia, Salvatore; Zinellu, Elisabetta; Bifulco, Fabiana; Pintus, Gianfranco; Mangoni, Arduino A; Carru, Ciriaco; Pirina, Pietro

    2016-02-01

    Chronic obstructive pulmonary disease (COPD) and asthma are both characterized by heterogeneous chronic airway inflammation and obstruction as well as oxidative stress (OS). However, it is unknown whether OS occurs in early disease and how to best assess its presence. Plasma OS markers (TBARS, PSH, taurine, GSH, ergothioneine and paraoxonase 1 activity) and lung function tests were measured in patients with mild stable asthma (n = 24) and mild stable COPD (n = 29) and in age- and sex-matched controls. Forced expiratory volume in 1 s (FEV1 ) was associated with age both in patients and control groups. By contrast, FEV1 was positively correlated with PSH only in COPD (ρ = 0·49, P = 0·007). In multiple logistic regression analysis, lower PSH was the only OS marker independently associated with increased odds of both asthma (OR = 0·32, 95% CI 0·13-0·78, P = 0·01) and COPD (OR = 0·50, 95% CI 0·26-0·95, P = 0·03). These findings suggest that proteins -SH are a sensitive OS marker in early COPD and asthma.

  1. Immunological Roles of Elevated Plasma Levels of Matricellular Proteins in Japanese Patients with Pulmonary Tuberculosis

    Directory of Open Access Journals (Sweden)

    Beata Shiratori

    2016-12-01

    Full Text Available Elevated matricellular proteins (MCPs, including osteopontin (OPN and galectin-9 (Gal-9, were observed in the plasma of patients with Manila-type tuberculosis (TB previously. Here, we quantified plasma OPN, Gal-9, and soluble CD44 (sCD44 by enzyme-linked immunosorbent assay (ELISA, and another 29 cytokines by Luminex assay in 36 patients with pulmonary TB, six subjects with latent tuberculosis (LTBI, and 19 healthy controls (HCs from Japan for a better understanding of the roles of MCPs in TB. All TB subjects showed positive results of enzyme-linked immunospot assays (ELISPOTs. Spoligotyping showed that 20 out of 36 Mycobacterium tuberculosis (MTB strains belong to the Beijing type. The levels of OPN, Gal-9, and sCD44 were higher in TB (positivity of 61.1%, 66.7%, and 63.9%, respectively than in the HCs. Positive correlations between OPN and Gal-9, between OPN and sCD44, and negative correlation between OPN and ESAT-6-ELISPOT response, between chest X-ray severity score of cavitary TB and ESAT-6-ELISPOT response were observed. Instead of OPN, Gal-9, and sCD44, cytokines G-CSF, GM-CSF, IFN-α, IFN-γ, IL-12p70, and IL-1RA levels were higher in Beijing MTB-infected patients. These findings suggest immunoregulatory, rather than inflammatory, effect of MCPs and can advance the understanding of the roles of MCPs in the context of TB pathology.

  2. Comprehensive antigen screening identifies Moraxella catarrhalis proteins that induce protection in a mouse pulmonary clearance model.

    Directory of Open Access Journals (Sweden)

    Margarita Smidt

    Full Text Available Moraxella catarrhalis is one of the three most common causative bacterial pathogens of otitis media, however no effective vaccine against M. catarrhalis has been developed so far. To identify M. catarrhalis vaccine candidate antigens, we used carefully selected sera from children with otitis media and healthy individuals to screen small-fragment genomic libraries that are expressed to display frame-selected peptides on a bacterial cell surface. This ANTIGENome technology led to the identification of 214 antigens, 23 of which were selected by in vitro or in vivo studies for additional characterization. Eight of the 23 candidates were tested in a Moraxella mouse pulmonary clearance model, and 3 of these antigens induced significantly faster bacterial clearance compared to adjuvant or to the previously characterized antigen OmpCD. The most significant protection data were obtained with the antigen MCR_1416 (Msp22, which was further investigated for its biological function by in vitro studies suggesting that Msp22 is a heme binding protein. This study comprises one of the most exhaustive studies to identify potential vaccine candidate antigens against the bacterial pathogen M. catarrhalis.

  3. Research advance on interstitial lung disease in patient with rheumatoid arthritis and serum surfactant proteins%类风湿关节炎合并间质性肺病及血清表面活性蛋白研究进展

    Institute of Scientific and Technical Information of China (English)

    宋庆珍; 高惠英

    2012-01-01

    The interstitial lung disease can usually be discovered in rheumatoid arthritis,and it has high incidence rate and case fatality.It can be misdiagnosis and missed diagnosis in early period,and appearance pulmonary interstitial fibrosis in end,which is very difficult to treat in clinic.Recent years,there are more research of serum surfactant protein in interstitial lung disease.This articles will review the diagnosis and treatment progress of interstitial lung disease complicated by rheumatoid arthritis,and research advance of serum surfactant proteins on interstitial lung disease,so that provide new approach of early diagnosis and therapeutic efficacy observation of this disease.%类风湿关节炎合并间质性肺病发病率、病死率高,早期易误诊、漏诊,尤其后期出现肺间质纤维化,临床治疗很困难.近年来,血清表面活性蛋白在间质性肺病研究较多.本文基于对类风湿关节炎合并间质性肺病的诊断和治疗进展方面的现代认识及血清表面活性蛋白在间质性肺病的研究进展进行综述,为该疾病早期诊断和治疗效果观察提供新的方法和手段.

  4. 早期联合应用NCPAP和PS治疗新生儿呼吸窘迫综合征%Early Nasal Continuous Positive Airway Pressure And Pulmonary Surfactant Therapy For Neonatal Respiratory Distress Syndrome

    Institute of Scientific and Technical Information of China (English)

    周媛; 杨静; 王岩岩; 王李敏

    2012-01-01

    目的 讨论经鼻持续气道正压通气(NCPAP)联合肺表面活性物质(PS)治疗新生儿呼吸窘迫综合征(NRDS)的治疗效果.方法 应用NCPAP联合PS治疗25例呼吸窘迫综合征的新生儿,并对其临床特点、动脉血气分析进行分析.结果 23例发绀和呼吸困难症状均有所减轻或消失.X线表现肺透亮度明显改善,或病变未进展,血气分析参数明显改善.2例因病情加重放弃治疗.结论 NCPAP联合PS能迅速有效地治疗新生儿呼吸窘迫综合征.用这种方法通过阻止呼吸窘迫综合征的进展,降低了以后应用呼吸机的需要.细致观察和正确的护理也是治疗成功的关键.%Objective To investigate the effects of nasal continuous positive airway pressure ( NCPAP ) early combined with pul-monary surfactant ( PS ) on newborn with respiratory distress syndrome ( RDS ). Methods 25 cases of newborn with respiratory distress syndrome were treated by Curosurf ( 100 ~ 200 mg/kg, every times ) and then they were given breath support by NCPAP. The clinical characteristics and results of blood gas analysis were evaluated. Results The symptoms of cyanosis and breathing difficulties disappeared or were reduced in 23 cases. The lung permeability showed by X-ray was obviously improved. Because the condition became more serious, two cases gave up. Conclusions Early NCPAP combined with PS have a good effect for newborn with respiratory distress syndrome, and improving the survival rate. It can decrease the requirement for respiratory machine by preventing respiratory distress syndrome. The cor-rect nursing is the key of successful treatment.

  5. Efficacy of pulmonary surfactant in treatment of acute respiratory distress syndrome in full-term newborns%肺表面活性物质治疗足月新生儿急性呼吸窘迫综合征疗效观察

    Institute of Scientific and Technical Information of China (English)

    杨梅; 郑平; 李晶; 陶梦婕

    2012-01-01

    Objective To explore the clinical efficacy of the pulmonary surfactant replacement therapy for acute respiratory distress syndrome CARDS) in full-term neonates. Methods Twenty-six eligible full- term neonates with ARDS were recruited and randomly divided into two groups: treatment group (n=13) and control group (n=13). Infants in treatment group were injected with pulmonary surfactant 100 mg/Kg via tracheal intubation. The rest of the treatment measures were same in treatment and control groups. Results There were no differences between the two groups in gestational age. birth weight and primary disease. After the pulmonary surfaetant replacement therapy, the PaO2/FiO2 was higher in treatment group than that in control group at 2, 6, 12, 24 h after the treatment. The differences at all time points were statistically significant (P<0.05). The treatment group also had a significantly shorter oxygen treatment and hospitalization time (P<0.G5). Conclusions The application of the pulmonary surfactant replacement treatment in full-term infants with ARDS could improve oxygenation and thus yield better prognosis.%目的 探讨肺表面活性物质治疗足月新生儿急性呼吸窘迫综合征(ARDS)的临床疗效.方法纳入符合诊断标准的ARDS足月新生儿,随机分为2组,治疗组经气管插管注入肺表面活性物质100 mg/kg,其余治疗方案同对照组.结果共纳入26例ARDS足月新生儿,治疗组和对照组各13例,两组新生儿的胎龄、出生体质量、原发疾病差异无统计学意义.经肺表面活性物质治疗后,治疗组新生儿在治疗2、6、12、24 h时的PaO2/FiO2均高于对照组,差异有统计学意义(P<0.05);治疗组新生儿的用氧时间、住院时间均较对照组缩短,差异有统计学意义(P<0.05).结论应用肺表面活性物质治疗足月新生儿的ARDS可改善氧合功能,有利于改善预后.

  6. Different doses of pulmonary surfactant in treatment of neonatal respiratory distress syndrome%不同剂量 PS治疗新生儿呼吸窘迫综合征的临床研究

    Institute of Scientific and Technical Information of China (English)

    王昌燕; 裴怀腾; 余晓娟

    2015-01-01

    目的:比较不同剂量牛肺表面活性物质( PS)治疗新生儿呼吸窘迫综合征( NRDS)的疗效。方法选择2009年1月至2014年9月西电集团医院新生儿科收治的44例NRDS患儿,随机分为3组,均予国产牛肺表面活性物质治疗,首剂大剂量组100mg/kg为15例,中剂量组70mg/kg为14例,小剂量组40mg/kg为15例。比较3组的动脉血氧分压(PaO2)、肺泡动脉氧分压差[P(A-a)O2]、动脉血二氧化碳分压(PaCO2)、氧合指数(OI)、用药后通气时间、总用氧时间、肺部X线改变及常见并发症的发生率等。结果3组患儿治疗前一般情况无差异,应用PS治疗1h后,PaO2、P( A-a) O2较使用前明显好转,且组间比较差异有统计学意义(F值分别为5.752、7.184,均P<0.05);用药6h后,各组血气分析指标均出现显著改变,大剂量组PaCO2和OI均低于中、小剂量组(F值分别为6.215、8.341,均P<0.05);用药12h及24h后X线评分,大剂量组亦明显优于中、小剂量组(F值分别为8.233、6.865,均P<0.05)。应用PS次数、氧疗时间、通气时间、住院时间、治愈率3组比较差异均有统计学意义(χ2=7.325;F值分别为8.295、4.598、7.155;χ2=5.126,均P<0.05)。各组均无严重不良反应发生。结论用PS治疗NRDS时,尽可能满足首剂≥70mg/kg是安全有效的。%Objective To evaluate the clinical efficacy of different doses of bovine pulmonary surfactant (PS) in treatment of neonatal respiratory distress syndrome ( NRDS) .Methods A total of 44 infants with NRDS admitted in Xi’ an XD Group Hospital during the period of January 2009 to September 2014 were randomly divided into three different groups and treated with domestic bovine pulmonary surfactant (Calsurf).High dose group (15 cases) was given 100mg/kg for the first dose, middle dose group (14 cases) was given 70mg/kg, and low dose

  7. Lung Surfactant and Its Use in Lung Diseases

    Directory of Open Access Journals (Sweden)

    O. A. Rosenberg

    2007-01-01

    Full Text Available The review considers the present views of lung surfactant (LS functions with emphasis on its protective and barrier properties and ability to maintain local and adaptive immunity. The composition of commercial LS formulations is analyzed. Data on qualitative and quantitative LS abnormalities are presented in various diseases in neonates and adults. The results of clinical trials of different LS formulations in the treatment of acute respiratory distress syndrome in adults are analyzed in detail. Recent data on the results of and prospects for surfactant therapy for bronchial asthma, chronic obstructive pulmonary disease and pulmonary tuberculosis are given. 

  8. Controlling Nonspecific Protein Adsorption in a Plug-Based Microfluidic System by Controlling Interfacial Chemistry Using Fluorous-Phase Surfactants

    OpenAIRE

    Roach, L. Spencer; Song, Helen; Ismagilov, Rustem F.

    2005-01-01

    Control of surface chemistry and protein adsorption is important for using microfluidic devices for biochemical analysis and high-throughput screening assays. This paper describes the control of protein adsorption at the liquid-liquid interface in a plug-based microfluidic system. The microfluidic system uses multiphase flows of immiscible fluorous and aqueous fluids to form plugs, which are aqueous droplets that are completely surrounded by fluorocarbon oil and do not come into direct contac...

  9. Effect of low doses of lipopolysaccharide prior to ozone exposure οn bronchoalveolar lavage. Differences between wild type and surfactant protein A-deficient mice

    Directory of Open Access Journals (Sweden)

    Rizwanul Haque

    2009-01-01

    Full Text Available SUMMARY. BACKGROUND: Several aspects of the inflammatory response to a single insult, i.e., exposure to 2 ppm of ozone (O3 for 3 h or 6 h, are less pronounced in surfactant protein A deficient (SP-A -/- mice (KO than in wild type mice (WT. It was hypothesized that a mild insult, specifically low doses of lipopolysaccharide (LPS, would adversely affect host defense and differentially potentiate O3-induced injury in WT and KO mice. METHODS: WT and KO mice were treated with different doses of LPS or LPS (2 ng + O3 (2 ppm or filtered air (FA for 3 h, then sacrificed 4 h following exposure (O3, FA or 20 h after LPS treatment alone. Several endpoints of inflammation were measured in bronchoalveolar lavage (BAL. RESULTS: 1 At 20 h after LPS treatment alone, both WT and KO mice exhibited signs of inflammation, but with differences in the macrophage inflammatory protein 2 (MIP-2 response pattern, total cells (at 0.5 ng LPS and basal levels of oxidized protein and phospholipids; 2 After LPS + O3, KO compared to WT showed decrease in polymorphonuclear leukocytes (PMNs and MIP-2 and increase in phospholipids, and after LPS + FA an increase in total cells; 3 WT after LPS + FA showed an increase in SP-A with no further increase after LPS + O3, and an increase in oxidized SP-A dimer following O3 or LPS + O3. CONCLUSIONS: LPS treatment has negative effects on inflammation endpoints in mouse BAL long after exposure and renders KO mice less capable of responding to a second insult. LPS and O3 affect SP-A, quantitatively and qualitatively, respectively. Pneumon 2009; 22(2:131–155.

  10. Concentration of surfactant protein D, Clara cell protein CC-16 and IL-10 in bronchoalveolar lavage (BAL in patients with sarcoidosis, hypersensivity pneumonitis and idiopathic pulmonary fibrosis.

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    Wojciech Naumnik

    2009-12-01

    Full Text Available The process of interstitial inflammation, often chronic, goes fluently from alveolitis through granuloma formation to irreversible fibrosis and lung remodeling. Eventually, the loss of functional alveolar units leads to chronic respiratory failure. The pneumoproteins (e.g. SP-D, CC-16 are considered to be markers of interstitial inflammation. We measured BAL concentration of SP-D, CC-16 and IL-10 in patients with sarcoidosis (27, IPF (7 and HP (9. The level of each marker was determined by ELISA specific kit. We found the highest SP-D and CC-16 BAL concentration in patients with the III stage of sarcoidosis (96,67 ng/ml and 31,78 ng/ml, respectively. The lowest SP-D concentration was observed in patients with IPF (76,49 ng/ml, and the lowest CC-16 concentration in patients with HP (21,39 ng/ml. The differences were not statistically significant. In the group of the III stage of sarcoidosis higher SP-D levels were related to higher BAL cytosis and higher percentage of BAL neutrophils, just the opposite as in the IPF and HP group. In the III stage of sarcoidosis and HP, the lower SP-D levels, the lower FEV1 and VC values. The results show, that in acute interstitial inflammation with larger parenchyma engagement (III stage of sarcoidosis the levels of SP-D were higher then in chronic interstitial inflammation (IPF.

  11. Crystal Structure of a Complex of Surfactant Protein D (SP-D) and Haemophilus influenzae Lipopolysaccharide Reveals Shielding of Core Structures in SP-D-Resistant Strains.

    Science.gov (United States)

    Clark, Howard W; Mackay, Rose-Marie; Deadman, Mary E; Hood, Derek W; Madsen, Jens; Moxon, E Richard; Townsend, J Paul; Reid, Kenneth B M; Ahmed, Abdul; Shaw, Amy J; Greenhough, Trevor J; Shrive, Annette K

    2016-05-01

    The carbohydrate recognition domains (CRDs) of lung collectin surfactant protein D (SP-D) recognize sugar patterns on the surface of lung pathogens and promote phagocytosis. Using Haemophilus influenzae Eagan strains expressing well-characterized lipopolysaccharide (LPS) surface structures of various levels of complexity, we show that bacterial recognition and binding by SP-D is inversely related to LPS chain extent and complexity. The crystal structure of a biologically active recombinant trimeric SP-D CRD complexed with a delipidated Eagan 4A LPS suggests that efficient LPS recognition by SP-D requires multiple binding interactions utilizing the three major ligand-binding determinants in the SP-D binding pocket, with Ca-dependent binding of inner-core heptose accompanied by interaction of anhydro-Kdo (4,7-anhydro-3-deoxy-d-manno-oct-2-ulosonic acid) with Arg343 and Asp325. Combined with enzyme-linked immunosorbent assays (ELISAs) and fluorescence-activated cell sorter (FACS) binding analyses, our results show that extended LPS structures previously thought to be targets for collectins are important in shielding the more vulnerable sites in the LPS core, revealing a mechanism by which pathogens with complex LPS extensions efficiently evade a first-line mucosal innate immune defense. The structure also reveals for the first time the dominant form of anhydro-Kdo.

  12. Surfactant Phosphatidylcholine Metabolism in Severe Neonatal Lung Disease: Studied with Stable Isotopes

    NARCIS (Netherlands)

    D.J.M.T. Janssen (Daphne)

    2003-01-01

    markdownabstract__Abstract__ Avery and Mead showed in 1959 that pulmonary surfactant deficiency is a major factor in the pathophysiology of respiratory distress syndrome (RDS). In 1980 Fujiwara et al. administered exogenous surfactant for the first time successfully to preterm infants with RDS

  13. Surfactant Phosphatidylcholine Metabolism in Severe Neonatal Lung Disease: Studied with Stable Isotopes

    NARCIS (Netherlands)

    D.J.M.T. Janssen (Daphne)

    2003-01-01

    markdownabstract__Abstract__ Avery and Mead showed in 1959 that pulmonary surfactant deficiency is a major factor in the pathophysiology of respiratory distress syndrome (RDS). In 1980 Fujiwara et al. administered exogenous surfactant for the first time successfully to preterm infants with RDS (2).

  14. Salmeterol/fluticasone treatment reduces circulating C-reactive protein level in patients with stable chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    TANG Yong-jiang; WANG Ke; YUAN Tao; QIU Ting; XIAO Jun; YI Qun; FENG Yu-lin

    2010-01-01

    Background Evidence suggests that systemic inflammation may play an important role in the progression and morbidity of chronic obstructive pulmonary disease. It remains controversial whether inhaled corticosteroid in combination with a long-acting β2-adrenoceptor agonist can attenuate systemic inflammation. We evaluated the effect of salmeterol/fluticasone propionate on circulating C-reactive protein level in stable chronic obstructive pulmonary disease patients.Methods An open-label clinical trial was conducted to recruit 122 outpatients with stable moderate-to-severe chronic obstructive pulmonary disease from department of respiratory medicine in two teaching hospitals between June 2007 and March 2008. Patients were randomized into two groups (1:1) to receive either the combination of 50 ug salmeterol and 500 ug fluticasone twice daily (n=61), or the combination of 206 ug albuterol and 36 ug ipratropium q.i.d (n=61) over 6 months. Circulating C-reactive protein concentrations were measured before randomization and during the follow-up. The efficacy of treatment was also assessed by spirometry, as well as health status and dyspnea score at baseline and after 6-month treatment.Results Baseline characteristics of two groups were similar. Compared with ipratropium/albuterol, the combination of salmeterol/fluticasone significantly reduced circulating level of C-reactive protein (-1.73 vs. 0.08 mg/L, respectively, P <0.05) after 6-month treatment. Forced expiratory volume in one second (FEV1) and health status also improved significantly in salmeterol/fluticasone group compared with ipratropium/albuterol. Salmeterol/fluticasone treatment subjects who had a decrease of circulating C-reactive protein level had a significant improvement in FEV1 and St George's Respiratory Questionnaire total scores compared with those who did not (185 vs. 83 ml and -5.71 vs. -1.79 units, respectively, both P<0.01).Conclusion Salmeterol/fluticasone treatment reduced circulating C

  15. An antibody against the surfactant protein A (SP-A)-binding domain of the SP-A receptor inhibits T cell-mediated immune responses to Mycobacterium tuberculosis.

    Science.gov (United States)

    Samten, Buka; Townsend, James C; Sever-Chroneos, Zvjezdana; Pasquinelli, Virginia; Barnes, Peter F; Chroneos, Zissis C

    2008-07-01

    Surfactant protein A (SP-A) suppresses lymphocyte proliferation and IL-2 secretion, in part, by binding to its receptor, SP-R210. However, the mechanisms underlying this effect are not well understood. Here, we studied the effect of antibodies against the SP-A-binding (neck) domain (alpha-SP-R210n) or nonbinding C-terminal domain (alpha-SP-R210ct) of SP-R210 on human peripheral blood T cell immune responses against Mycobacterium tuberculosis. We demonstrated that both antibodies bind to more than 90% of monocytes and 5-10% of CD3+ T cells in freshly isolated PBMC. Stimulation of PBMC from healthy tuberculin reactors [purified protein derivative-positive (PPD+)] with heat-killed M. tuberculosis induced increased antibody binding to CD3+ cells. Increased antibody binding suggested enhanced expression of SP-R210, and this was confirmed by Western blotting. The antibodies (alpha-SP-R210n) cross-linking the SP-R210 through the SP-A-binding domain markedly inhibited cell proliferation and IFN-gamma secretion by PBMC from PPD+ donors in response to heat-killed M. tuberculosis, whereas preimmune IgG and antibodies (alpha-SP-R210ct) cross-linking SP-R210 through the non-SP-A-binding, C-terminal domain had no effect. Anti-SP-R210n also decreased M. tuberculosis-induced production of TNF-alpha but increased production of IL-10. Inhibition of IFN-gamma production by alpha-SP-R210n was abrogated by the combination of neutralizing antibodies to IL-10 and TGF-beta1. Together, these findings support the hypothesis that SP-A, via SP-R210, suppresses cell-mediated immunity against M. tuberculosis via a mechanism that up-regulates secretion of IL-10 and TGF-beta1.

  16. Diagnostic utility of C-reactive Protein combined with brain natriuretic peptide in acute pulmonary edema: a cross sectional study

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    Murakami Junji

    2011-06-01

    Full Text Available Abstract Introduction Discriminating acute lung injury (ALI or acute respiratory distress syndrome (ARDS from cardiogenic pulmonary edema (CPE using the plasma level of brain natriuretic peptide (BNP alone remains controversial. The aim of this study was to determine the diagnostic utility of combination measurements of BNP and C-reactive protein (CRP in critically ill patients with pulmonary edema. Methods This was a cross-sectional study. BNP and CRP data from 147 patients who presented to the emergency department due to acute respiratory failure with bilateral pulmonary infiltrates were analyzed. Results There were 53 patients with ALI/ARDS, 71 with CPE, and 23 with mixed edema. Median BNP and CRP levels were 202 (interquartile range 95-439 pg/mL and 119 (62-165 mg/L in ALI/ARDS, and 691 (416-1,194 pg/mL (p Conclusions Measurement of CRP is useful as well as that of BNP for distinguishing ALI/ARDS from CPE. Furthermore, a combination of BNP and CRP can provide higher accuracy for the diagnosis.

  17. 气管内滴注肺表面活性物质治疗新生儿肺透明膜病效果分析%Analysis of Efficacy of Hyaline Membrane Disease of Newborn Treated with Pulmonary Surfactant by Endotracheal Instillation

    Institute of Scientific and Technical Information of China (English)

    陈燕霞; 罗素云; 廖艳霞

    2012-01-01

    Objective To study the efficacy and safety of pulmonary surfactant used in hyaline membrane disease(HMD)of newborn treatment.Methods 67 cases of HMD children were treated.And pulmonary surfactant was used by intratracheal instillation.Clinical manifestation,blood gas analysis,X-ray chest film and complication before and after treatment were observed and recorded.Results 65 cases of children were recovered and discharged(97.01%),while 2 cases were dead.The PO2 increased significantly after the surfactant was given(P<0.05),while the PCO2 decreased significantly(P<0.05),and situation of skin cyanosis was relieved.X-ray chest films in 24 hours showed that 62 cases were improved(92.54%),while 4 cases were not obvious(5.97%),and there was hemorrhage image in the last 1 caes(1.49%).There were 5 cases of complication,involving 3 cases of pneumonia,1 case of intracranial hemorrhage and 1 case of pulmonary hemorrhage.Conclusion Clinical symptoms could be impurved rapidly,pulmonary oxygenation could be ameliorated,the need of mechanical ventilation could be lower and the rate of incidence of complication and death could be reduced effectively by using pulmonary surfactant early.%目的 探讨气管内滴注肺表面活性物质治疗新生儿肺透明膜病的效果及安全性.方法 选择新生儿肺透明膜病患儿67例,采用气管内注入单剂肺表面活性物质治疗,观察患儿治疗前后的临床表现、血气、X线胸片以及并发症情况.结果 痊愈出院65例(97.01%),死亡2例;给药后患儿氧分压(PO2)和动脉血氧饱和度(SaO2)明显升高(P<0.05),二氧化碳分压(PCO2)明显下降(P<0.05),皮肤发绀、青紫状况缓解.24 h内复查胸片示肺野透明情况显著改善62例(92.54%),无明显改善4例(5.97%),有合并肺出血影像1例(1.49%).共发生并发症5例,其中肺炎3例,颅内出血1例,肺出血1例.结论 早期应用肺表面活性物质能快速改善肺透明膜病患儿的临床症状,改

  18. Concurrent administration of heparin and activated protein C in a patient with pulmonary embolism and severe sepsis with positive outcome

    Directory of Open Access Journals (Sweden)

    Juneja Deven

    2009-01-01

    Full Text Available Results of the PROWESS trial suggested that heparin may reduce the efficacy of recombinant human activated protein C (rhAPC and the XPRESS study also showed increased bleeding complications in patients receiving heparin with rhAPC. Although it has been shown that heparin prophylaxis may be used along with rhAPC, no study has shown the interaction between continuous heparin infusion and rhAPC. Here, we report a case of severe sepsis with pulmonary embolism who was concurrently administered heparin and rhAPC infusions, with positive results and no bleeding complications.

  19. Clinical utility of C-reactive protein to predict treatment response during cystic fibrosis pulmonary exacerbations

    Science.gov (United States)

    Sharma, Ashutosh; Kirkpatrick, Gordon; Chen, Virginia; Skolnik, Kate; Hollander, Zsuzsanna; Wilcox, Pearce; Quon, Bradley S.

    2017-01-01

    Rationale C-reactive protein (CRP) is a systemic marker of inflammation that correlates with disease status in cystic fibrosis (CF). The clinical utility of CRP measurement to guide pulmonary exacerbation (PEx) treatment decisions remains uncertain. Objectives To determine whether monitoring CRP during PEx treatment can be used to predict treatment response. We hypothesized that early changes in CRP can be used to predict treatment response. Methods We reviewed all PEx events requiring hospitalization for intravenous (IV) antibiotics over 2 years at our institution. 83 PEx events met our eligibility criteria. CRP levels from admission to day 5 were evaluated to predict treatment non-response, using a modified version of a prior published composite definition. CRP was also evaluated to predict time until next exacerbation (TUNE). Measurements and main results 53% of 83 PEx events were classified as treatment non-response. Paradoxically, 24% of PEx events were characterized by a ≥ 50% increase in CRP levels within the first five days of treatment. Absolute change in CRP from admission to day 5 was not associated with treatment non-response (p = 0.58). Adjusted for FEV1% predicted, admission log10 CRP was associated with treatment non-response (OR: 2.39; 95% CI: 1.14 to 5.91; p = 0.03) and shorter TUNE (HR: 1.60; 95% CI: 1.13 to 2.27; p = 0.008). The area under the receiver operating characteristics (ROC) curve of admission CRP to predict treatment non-response was 0.72 (95% CI 0.61–0.83; p 75 mg/L with a specificity of 90% for treatment non-response. Conclusions Admission CRP predicts treatment non-response and time until next exacerbation. A very elevated admission CRP (>75mg/L) is highly specific for treatment non-response and might be used to target high-risk patients for future interventional studies aimed at improving exacerbation outcomes. PMID:28178305

  20. Clinical Study of Therapy for Neonatal Respiratory Distress Syndrome with Pulmonary Surfactant and CPAP%肺表面活性物质联合鼻塞持续正压通气治疗新生儿呼吸窘迫综合征临床观察

    Institute of Scientific and Technical Information of China (English)

    秦素芳; 蔡家平; 严璃

    2012-01-01

    Objective: To study the clinical effect of pulmonary surfactant (Curosurf) and CPAP on neonatal respiratory distress syndrome. Methods: Randomly 36 cases of newborn infants admitted into Yueyang Women and Children's Hospital from January 2009 to June 2011 with a confirmed diagnosis of neonatal respiratory distress syndrome were analyzed, who were treated with pulmonary surfactant and continuous positive airway pressure ( CACP) , and then the clinical syndrome and blood gas analysis of these infants, the readings of the ventilator as well as the complications were studied. Results: The clinical syndrome of newborn infants were improved evidently or disappeared, and PO2, PCO2 and pH were improved significantly (P<0. 01). Conclusions: The combination of pulmonary surfactant and CPAP could significantly improve the neonatal respiratory distress syndrome within the primary treatment.%目的:探讨应用肺表面活性物质(固尔苏)联合鼻塞持续正压通气(CPAP)治疗新生儿呼吸窘迫综合征的临床疗效.方法:随机选取2009年1月~2011年6月我科新生儿病房入院确诊为新生儿呼吸窘迫综合征的患儿36例,使用肺表面活性物质联合CPAP治疗,观察治疗前后患儿临床症状及血气分析、呼吸机参数的变化及并发症情况.结果:用药后临床症状明显减轻,PO2 、PCO2 、pH、FiO2、PEEP均较用药前明显改善,差异有统计学意义(P<0.01).结论:肺表面活性物质联合CPAP治疗新生儿呼吸窘迫综合征疗效显著,便于开展.

  1. Post-translational processing of surfactant protein-C proprotein: targeting motifs in the NH(2)-terminal flanking domain are cleaved in late compartments.

    Science.gov (United States)

    Johnson, A L; Braidotti, P; Pietra, G G; Russo, S J; Kabore, A; Wang, W J; Beers, M F

    2001-03-01

    Rat surfactant protein (SP)-C is a 3.7-kD hydrophobic lung-specific protein generated from proteolytic processing of a 21-kD propeptide (SP-C(21)). We have demonstrated that initial post-translational processing of SP-C(21) involves two cleavages of the COOH-terminus (Beers and colleagues, J. Biol. Chem. 1994;269:20,318--20,328). The goal of the current study was to define processing and function of the NH(2)-terminal flanking domain. Epitope-specific antisera directed against spatially distinct regions of the NH(2) terminus, NPROSP-C(2-9) (epitope = D(2)-L(9)) and NPROSP-C(11-23) (= E(11)-Q(23)) were produced. By Western blotting, both antisera identified SP-C(21) in microsomes. A 6-kD form (SP-C(6)), enriched in lamellar bodies (LBs), was detected only by NPROSP-C(11-23) and not extractable with NaCO(3) treatment. Immunogold staining of ultrathin lung sections with NPROSP-C(11-23) identified proSP-C in both multivesicular bodies (mvb) and LBs whereas NPROSP-C(2-9) labeled only mvb. (35)S-pulse chase analysis demonstrated synthesis of SP-C(21) and three intermediate forms (SP-C(16), SP-C(7), and SP-C(6)). Complete processing involved four separate cleavages with a precursor- product relationship between the low molecular weight forms SP-C(7) and SP-C(6). Fluorescence microscopy of A549 cells expressing fusion proteins of enhanced green fluorescent protein (EGFP) and proSP-C NH(2)-terminal deletion mutants showed targeting of EGFP/SP-C(1-194) and EGFP/SP-C(10-194) to early endosomal antigen-1-negative, CD-63-positive cytoplasmic vesicles whereas EGFP/SP-C(19-194), EGFP/SP-C(Delta 10-18), and EGFP/SP-C(24-194) were restricted to the endoplasmic reticulum (ER). We conclude that synthetic processing includes a previously unrecognized cleavage of the proximal NH(2) terminus (M(1)-L(9)), which occurs after removal of COOH-flanking domains (H(59)-I(194)) but before packaging in LBs, and that the region M(10)-T(18) is required for targeting of proSP-C to post-ER vesicular

  2. Surfactants in tribology

    CERN Document Server

    Biresaw, Girma

    2014-01-01

    Surface science and tribology play very critical roles in many industries. Manufacture and use of almost all consumer and industrial products rely on the application of advanced surface and tribological knowledge. The fourth in a series, Surfactants in Tribology, Volume 4 provides an update on research and development activities connecting surfactants and tribological phenomena. Written by renowned subject matter experts, the book demonstrates how improved design of surfactants can be harnessed to control tribological phenomena. Profusely illustrated and copiously referenced, the chapters also

  3. Dendrimer-surfactant interactions.

    Science.gov (United States)

    Cheng, Yiyun; Zhao, Libo; Li, Tianfu

    2014-04-28

    In this article, we reviewed the interactions between dendrimers and surfactants with particular focus on the interaction mechanisms and physicochemical properties of the yielding dendrimer-surfactant aggregates. In order to provide insight into the behavior of dendrimers in biological systems, the interactions of dendrimers with bio-surfactants such as phospholipids in bulk solutions, in solid-supported bilayers and at the interface of phases or solid-states were discussed. Applications of the dendrimer-surfactant aggregates as templates to guide the synthesis of nanoparticles and in drug or gene delivery were also mentioned.

  4. Surfactant Sector Needs Urgent Readjustment

    Institute of Scientific and Technical Information of China (English)

    Huang Hongzhou

    2007-01-01

    @@ Surfactant industrial system has been basically established After 50 years' development, China has already established a surfactant industrial system with a relatively complete product portfolio and can produce 4714 varieties of surfactants in cationic,anionic, nonionic and amphoteric categories.

  5. Circulating surfactant protein -D is low and correlates negatively with systemic inflammation in early, untreated rheumatoid arthritis

    DEFF Research Database (Denmark)

    Christensen, Anne Friesgaard; Sørensen, Grith Lykke; Hørslev-Petersen, Kim

    2010-01-01

    changes in SP-D and CRP (zero to four years). SP-D was not associated to x-ray findings. CONCLUSIONS: This study confirms that circulating SP-D is persistently subnormal in early and untreated RA despite a favourable therapeutic response obtained during four years of follow-up. SP-D correlated negatively...... inflammation. Previously, we reported low circulating SP-D in early rheumatoid arthritis (RA), and the present investigation aims to extend these data by serial SP-D serum measurements, studies on synovial fluid, SP-D size distribution and genotyping in patients with early RA. METHODS: One......-hundred-and-sixty disease-modifying antirheumatic drug (DMARD) naïve RA patients with disease duration less than six months were studied prospectively for four years (CIMESTRA (Ciclosporine, Methotrexate, Steroid in RA) trial) including disease activity measures (C-reactive protein, joint counts and Health Assessment...

  6. Polymorphism in SFTPD gene affects assembly and constitutional serum levels of surfactant protein D in a Lebanese population

    DEFF Research Database (Denmark)

    Fakih, Dalia; Chamat, Soulaima; Medlej-Hashim, Myrna;

    2014-01-01

    the distribution profile of serum constitutional SP-D in the Lebanese population and to investigate the genetic influence of single nucleotide polymorphism (SNP) rs721917 within SP-D gene (SFTPD) on its multimerization and its serum basal level. The C/T alleles at this SNP level lead respectively either...... to a threonine or methionine at position 11 of the SP-D protein. SP-D was measured by ELISA in serum taken from 97 healthy subjects. The p.Met11Thr SNP was genotyped. Different forms of SP-D were separated by gel filtration chromatography. Basal serum SP-D levels varied extensively, over a range of 108.3 ng...

  7. Adsorption of surfactant protein D from human respiratory secretions by carbon nanotubes and polystyrene nanoparticles depends on nanomaterial surface modification and size.

    Science.gov (United States)

    Marchetti, Magda; Shaffer, Milo S P; Zambianchi, Martina; Chen, Shu; Superti, Fabiana; Schwander, Stephan; Gow, Andrew; Zhang, Junfeng Jim; Chung, Kian Fan; Ryan, Mary P; Porter, Alexandra E; Tetley, Teresa D

    2015-02-05

    The alveolar respiratory unit constitutes one of the main targets of inhaled nanoparticles; the effect of engineered nanomaterials (NMs) on human health is largely unknown. Surfactant protein D (SP-D) is synthesized by alveolar type II epithelial cells and released into respiratory secretions; its main function is in immune defence, notably against inhaled microbes. SP-D also plays an important role in modulating an appropriate inflammatory response in the lung, and reduced SP-D is associated with a number of inflammatory lung diseases. Adsorption of SP-D to inhaled NMs may facilitate their removal via macrophage phagocytosis. This study addresses the hypothesis that the chemistry, size and surface modification of engineered NMs will impact on their interaction with, and adsorption of, SP-D. To this purpose, we have examined the interactions between SP-D in human lung lavage and two NMs, carbon nanotubes and polystyrene nanoparticles, with different surface functionalization. We have demonstrated that particle size, functionalization and concentration affect the adsorption of SP-D from human lung lavage. Functionalization with negatively charged groups enhanced the amount of SP-D binding. While SP-D binding would be expected to enhance macrophage phagocytosis, these results suggest that the degree of binding is markedly affected by the physicochemistry of the NM and that deposition of high levels of some nanoparticles within the alveolar unit might deplete SP-D levels and affect alveolar immune defence mechanisms. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  8. 14-3-3 isoforms bind directly exon B of the 5'-UTR of human surfactant protein A2 mRNA.

    Science.gov (United States)

    Noutsios, Georgios T; Ghattas, Paul; Bennett, Stephanie; Floros, Joanna

    2015-07-15

    Human surfactant protein (SP) A (SP-A), an innate immunity molecule, is encoded by two genes, SFTPA1 and SFTPA2. The 5'-untranslated splice variant of SP-A2 (ABD), but not SP-A1 (AD), contains exon B (eB). eB is an enhancer for transcription and translation and contains cis-regulatory elements. Specific trans-acting factors, including 14-3-3, bind eB. The 14-3-3 protein family contains seven isoforms that have been found by mass spectrometry in eB electromobility shift assays (Noutsios et al. Am J Physiol Lung Cell Mol Physiol 304: L722-L735, 2013). We used four different approaches to investigate whether 14-3-3 isoforms bind directly to eB. 1) eB RNA pulldown assays showed that 14-3-3 isoforms specifically bind eB. 2) RNA electromobility shift assay complexes were formed using purified 14-3-3 isoforms β, γ, ε, η, σ, and τ, but not isoform ζ, with wild-type eB RNA. 3 and 4) RNA affinity chromatography assays and surface plasmon resonance analysis showed that 14-3-3 isoforms β, γ, ε, η, σ, and τ, but not isoform ζ, specifically and directly bind eB. Inhibition of 14-3-3 isoforms γ, ε, η, and τ/θ with shRNAs in NCI-H441 cells resulted in downregulation of SP-A2 levels but did not affect SP-A1 levels. However, inhibition of 14-3-3 isoform σ was correlated with lower levels of SP-A1 and SP-A2. Inhibition of 14-3-3 isoform ζ/δ, which does not bind eB, had no effect on expression levels of SP-A1 and SP-A2. In conclusion, the 14-3-3 protein family affects differential regulation of SP-A1 and SP-A2 by binding directly to SP-A2 5'-UTR mRNA.

  9. Elevated plasma surfactant protein D (SP-D) levels and a direct correlation with anti-severe acute respiratory syndrome coronavirus-specific IgG antibody in SARS patients

    DEFF Research Database (Denmark)

    Wu, Y P; Liu, Z H; Wei, R

    2009-01-01

    Pulmonary SP-D is a defence lectin promoting clearance of viral infections. SP-D is recognized to bind the S protein of SARS-CoV and enhance phagocytosis. Moreover, systemic SP-D is widely used as a biomarker of alveolar integrity. We investigated the relation between plasma SP-D, SARS-type pneum...

  10. Pulmonary edema

    Science.gov (United States)

    ... congestion; Lung water; Pulmonary congestion; Heart failure - pulmonary edema ... Pulmonary edema is often caused by congestive heart failure . When the heart is not able to pump efficiently, blood ...

  11. 精氨酸甲基转移酶与肺部疾病%Protein arginine methyltransferases and pulmonary diseases

    Institute of Scientific and Technical Information of China (English)

    梁彦超; 陈哲; 陈燕

    2014-01-01

    Protein arginine methyltransferases (PRMTs) are enzymes that catalyze the transfer of a methyl group from S-adenosyl-L-methionine into a guanidino nitrogen of protein arginine.Protein arginine methylation is a novel posttranslational modification that plays a pivotal role in a variety of intracellular events,such as DNA repair,RNA processing,transcriptional regulation,and signal transduction.Recently,many studies reveal that PRMTs are significantly associated with pulmonary diseases,cardiovascular diseases,cancer,infections,glucose metabolic diseases,and autoimmune diseases.The paper introduces the recent progresses in the influence of dysregulation of PRMTs on pulmonary diseases.%蛋白质精氨酸甲基转移酶(protein arginine methyltransferases,PRMTs)是催化S-腺苷-甲硫氨酸的甲基转移至蛋白质精氨酸胍基氮原子上的酶.精氨酸甲基化是一种重要的翻译后修饰方式,参与许多重要的细胞过程,包括DNA修复、RNA加工、转录调控和信号转导.近年来大量研究证实,PRMTs与呼吸系统疾病、心血管系统疾病、肿瘤、病毒感染、糖代谢及其相关疾病、自身免疫性疾病密切相关.明确PRMTs的异常表达对肺部疾病的影响对疾病的治疗有重要作用.

  12. SURFACTANTS IN LUBRICATION

    Science.gov (United States)

    Surfactants are one of the most widely applied materials by consumers and industry. The application areas for surfactants span from everyday mundane tasks such as cleaning, to highly complex processes involving the formulation of pharmaceuticals, foods, pesticides, lubricants, etc. Even though sur...

  13. Dynamic covalent surfactants

    NARCIS (Netherlands)

    Minkenberg, C.B.

    2012-01-01

    In this thesis the development of surfactant aggregates with fast exchange dynamics between the aggregated and non-aggregated state is described. Dynamic surfactant exchange plays an important role in natural systems, for instance in cell signaling, cell division, and uptake and release of cargo. Re

  14. Progress in the research on drug delivery method of pulmonary surfactant for treating respiratory distress syndrome%肺表面活性物质治疗呼吸窘迫综合征给药方式的研究进展

    Institute of Scientific and Technical Information of China (English)

    闫亚敏; 李忆东; 龚梅; 王志红

    2012-01-01

    Pulmonary surfactant (PS) is commonly used as a life-saving strategy in treating respiratory distress syndrome of newborn. However, its efficacy on patients with acute lung injury or acute respiratory distress syndrome is still controversial. The key factor that affects the efficacy of PS is the method for drug delivery. Current methods for PS delivery include instillation through endotracheal intubation or bronchoscopy and ultrasonic atomizing inhalation. All of them display advantages as well as disadvantages. Seeking simple, noninvasive, effective method for PS delivery is the direction for future study.%肺表面活性物质(pulmonary surfactant,PS)作为一种“救命药”已常规用于新生儿呼吸窘迫综合征的防治,但对急性肺损伤/急性呼吸窘迫综合征的治疗效果仍存在一定的争议.PS的给药方式作为影响其疗效的关键因素受到了医学界的广泛重视,现有的PS给药方法主要有气管导管滴入法、经纤维支气管镜滴入法和超声雾化吸入法,各有优缺点,而操作简便的、非侵袭性的、有效的给药方式是未来继续研究的方向.

  15. Pulmonary Thromboembolism in Klinefelter%u2019s Syndrome Patient with Deficient of Protein C

    OpenAIRE

    Mehmet Yigit

    2013-01-01

    Klinefelter syndrome (KS) is a common genetic disorder caused by one or more supernumerary X chromosomes. KS poses an increased risk for venous thromboembolic events such as deep venous thrombosis and pulmonary embolism. Klinefelter syndrome is prone to hypercoagulability due to hormonal imbalance and one or more inherited thrombophilic factors. Therefore, patients with KS having a medical history of venous thromboembolism require chest computed tomographic (CT) images and oral anticoagulatio...

  16. Epithelial Gpr116 regulates pulmonary alveolar homeostasis via Gq/11 signaling

    OpenAIRE

    Brown, Kari; Filuta, Alyssa; Ludwig, Marie-Gabrielle; Seuwen, Klaus; Jaros, Julian; Vidal, Solange; Arora, Kavisha; Naren, Anjaparavanda P.; Kandasamy, Kathirvel; Parthasarathi, Kaushik; Offermanns, Stefan; Mason, Robert J; Miller, William E.; Whitsett, Jeffrey A.; Bridges, James P.

    2017-01-01

    Pulmonary function is dependent upon the precise regulation of alveolar surfactant. Alterations in pulmonary surfactant concentrations or function impair ventilation and cause tissue injury. Identification of the molecular pathways that sense and regulate endogenous alveolar surfactant concentrations, coupled with the ability to pharmacologically modulate them both positively and negatively, would be a major therapeutic advance for patients with acute and chronic lung diseases caused by disru...

  17. Impaired Pulmonary Defense Against Pseudomonas aeruginosa in VEGF Gene Inactivated Mouse Lung

    Science.gov (United States)

    Breen, Ellen C.; Malloy, Jaret L.; Tang, Kechun; Xia, Feng; Fu, Zhenxing; Hancock, Robert E. W.; Overhage, Joerg; Wagner, Peter D.; Spragg, Roger G.

    2012-01-01

    Repeated bacterial and viral infections are known to contribute to worsening lung function in several respiratory diseases, including asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD). Previous studies have reported alveolar wall cell apoptosis and parenchymal damage in adult pulmonary VEGF gene ablated mice. We hypothesized that VEGF expressed by type II cells is also necessary to provide an effective host defense against bacteria in part by maintaining surfactant homeostasis. Therefore, Pseudomonas aeruginosa (PAO1) levels were evaluated in mice following lung-targeted VEGF gene inactivation, and alterations in VEGF-dependent type II cell function were evaluated by measuring surfactant homeostasis in mouse lungs and isolated type II cells. In VEGF-deficient lungs increased PAO1 levels and pro-inflammatory cytokines, TNFα and IL-6, were detected 24 hours after bacterial instillation compared to control lungs. In vivo lung-targeted VEGF gene deletion (57% decrease in total pulmonary VEGF) did not alter alveolar surfactant or tissue disaturated phosphatidylcholine (DSPC) levels. However, sphingomyelin content, choline phosphate cytidylyltransferase (CCT) mRNA and SP-D expression were decreased. In isolated type II cells an 80% reduction of VEGF protein resulted in decreases in total phospholipids (PL), DSPC, DSPC synthesis, surfactant associated proteins (SP)-B and -D, and the lipid transporters, ABCA1 and Rab3D. TPA-induced DSPC secretion and apoptosis were elevated in VEGF-deficient type II cells. These results suggest a potential protective role for type II cell-expressed VEGF against bacterial initiated infection. PMID:22718316

  18. 不同肺表面活性物质对新生儿呼吸窘迫综合征患儿影响的对比研究%Comparative Study for Influence on Neonatal Respiratory Distress Syndrome between Different Pulmonary Surfactants

    Institute of Scientific and Technical Information of China (English)

    刘春枝; 梅花

    2016-01-01

    目的:比较猪肺表面活性物质和牛肺表面活性物质对新生儿呼吸窘迫综合征患儿的影响。方法前瞻性收集内蒙古医科大学附属医院儿科2012—2015年收治的新生儿呼吸窘迫综合征患儿80例,根据随机对照原则分为对照组和研究组,每组40例。两组患儿均给予持续气道正压通气(CPAP),对照组患儿给予牛肺表面活性物质治疗,研究组患儿给予猪肺表面活性物质治疗。比较两组患儿治疗前、治疗24 h 后血气分析〔动脉血氧分压(PaO2)、动脉血二氧化碳分压(PaCO2)、pH 值〕,CPAP 持续时间、给氧时间及住院时间,观察两组患儿并发症发生情况和院内死亡情况。结果治疗前及治疗24 h 后两组患儿 PaO2、PaCO2和 pH 值比较,差异无统计学意义(P >0.05);治疗24 h后,两组患儿 PaO2和 pH 值高于治疗前,PaCO2低于治疗前(P 0.05)。结论与牛肺表面活性物质相比,猪肺表面活性物质治疗新生儿呼吸窘迫综合征患儿可更有效地缩短 CPAP 持续时间、给氧时间和住院时间。%Objective To compare the influence on neonatal respiratory distress syndrome( NRDS) between pig pulmonary surfactant and cow pulmonary surfactant. Methods A total of 80 newborns with NRDS were prospectively collected in the Affiliated Hospital of Inner Mongolia Medical University from 2012 to 2015,and they were divided into control group and study group according to randomized controlled principle,each of 40 cases. Based on continuous positive airway pressure ventilation,newborns of control group received cow pulmonary surfactant,newborns of study group received pig pulmonary surfactant. Blood - gas analysis results( including PaO2 ,PaCO2 and pH) before treatment and after 24 hours of treatment, duration of continuous positive airway pressure ventilation and oxygen inhalation,hospital stays,incidence of complications and in - hospital death were compared

  19. Design-based stereological analysis of the lung parenchymal architecture and alveolar type II cells in surfactant protein A and D double deficient mice

    DEFF Research Database (Denmark)

    Jung, A; Allen, L; Nyengaard, Jens Randel

    2005-01-01

    overlapping as well as distinct functions. The present study provides a design-based stereological analysis of adult mice deficient in both SP-A and SP-D (A(-)D(-)) with special emphasis on parameters characterizing alveolar architecture and surfactant-producing type II cells. Compared to wild-type, A......, but the mean volume of a single lamellar body remains constant. These results demonstrate that chronic deficiency of SP-A and SP-D in mice leads to parenchymal remodeling, type II cell hyperplasia and hypertrophy, and disturbed intracellular surfactant metabolism. The design-based stereological approach...

  20. Identification of Oxidative Stress Related Proteins as Biomarkers for Lung Cancer and Chronic Obstructive Pulmonary Disease in Bronchoalveolar Lavage

    Directory of Open Access Journals (Sweden)

    Amancio Carnero

    2013-02-01

    Full Text Available Lung cancer (LC and chronic obstructive pulmonary disease (COPD commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. Cigarette smoke causes oxidative stress and an inflammatory response in lung cells, which in turn may be involved in COPD and lung cancer development. The aim of this study was to identify differential proteomic profiles related to oxidative stress response that were potentially involved in these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL of 60 patients classified in four groups: COPD, COPD and LC, LC, and control (neither COPD nor LC. Proteins were separated into spots by two dimensional polyacrylamide gel electrophoresis (2D-PAGE and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF. A total of 16 oxidative stress regulatory proteins were differentially expressed in BAL samples from LC and/or COPD patients as compared with the control group. A distinct proteomic reactive oxygen species (ROS protein signature emerged that characterized lung cancer and COPD. In conclusion, our findings highlight the role of the oxidative stress response proteins in the pathogenic pathways of both diseases, and provide new candidate biomarkers and predictive tools for LC and COPD diagnosis.

  1. Immunohistochemical analyses of a case of extralobar pulmonary sequestration with chest pain in an adult

    Directory of Open Access Journals (Sweden)

    Yuji Ohtsuki

    2013-01-01

    Full Text Available Computed tomography of a Japanese man in his mid-forties with a complaint of right-side chest pain showed a dome-shaped smooth-surfaced mediastinal mass, which was extirpated. The cut surface was highly hemorrhagic and necrotic and not related to the original pulmonary tissues. Although routine sectioning detected bronchial cartilage, immunohistochemical analyses clearly showed the presence of alveolar type II cells; only the alveolar type II cells located at the periphery of this mass showed positive staining for cytokeratins, thyroid transcription factor 1, surfactant protein A, epithelial membrane antigen and Krebs von den Lungen-6. Thus, these analyses are useful for the detection of pulmonary components, even in severely hemorrhagic and necrotic tissues with marked sequestration. The clinical diagnosis was a rare, adult type of extralobar pulmonary sequestration accompanied by chest pain.

  2. Immunization with recombinant Pb27 protein reduces the levels of pulmonary fibrosis caused by the inflammatory response against Paracoccidioides brasiliensis.

    Science.gov (United States)

    Morais, Elis Araujo; Martins, Estefânia Mara do Nascimento; Boelone, Jankerle Neves; Gomes, Dawidson Assis; Goes, Alfredo Miranda

    2015-02-01

    Paracoccidioidomycosis (PCM) is a systemic mycosis in which the host response to the infectious agent typically consists of a chronic granulomatous inflammatory process. This condition causes lesions that impair lung function and lead to chronic pulmonary insufficiency resulting from fibrosis development, which is a sequel and disabling feature of the disease. The rPb27 protein has been studied for prophylactic and therapeutic treatment against PCM. Previous studies from our laboratory have shown a protective effect of rPb27 against PCM. However, these studies have not determined whether rPb27 immunization prevents lung fibrosis. We therefore conducted this study to investigate fibrosis resulting from infection by Paracoccidioides brasiliensis in the lungs of animals immunized with rPb27. Animals were immunized with rPb27 and subsequently infected with a virulent strain of P. brasiliensis. Fungal load was evaluated by counting colony-forming units, and Masson's trichrome staining was performed to evaluate fibrosis at 30 and 90 days post-infection. The levels of CCR7, active caspase 3, collagen and cytokines were analyzed. At the two time intervals mentioned, the rPb27 group showed lower levels of fibrosis on histology and reduced levels of collagen and the chemokine receptor CCR7 in the lungs. CCR7 was detected at higher levels in the control groups that developed very high levels of pulmonary fibrosis. Additionally, the immunized groups showed high levels of active caspase 3, IFN-γ, TGF-β and IL-10 in the early phase of P. brasiliensis infection. Immunization with Pb27, in addition to its protective effect, was shown to prevent pulmonary fibrosis.

  3. Improved Detection of Invasive Pulmonary Aspergillosis Arising during Leukemia Treatment Using a Panel of Host Response Proteins and Fungal Antigens.

    Directory of Open Access Journals (Sweden)

    Allan R Brasier

    Full Text Available Invasive pulmonary aspergillosis (IPA is an opportunistic fungal infection in patients undergoing chemotherapy for hematological malignancy, hematopoietic stem cell transplant, or other forms of immunosuppression. In this group, Aspergillus infections account for the majority of deaths due to mold pathogens. Although early detection is associated with improved outcomes, current diagnostic regimens lack sensitivity and specificity. Patients undergoing chemotherapy, stem cell transplantation and lung transplantation were enrolled in a multi-site prospective observational trial. Proven and probable IPA cases and matched controls were subjected to discovery proteomics analyses using a biofluid analysis platform, fractionating plasma into reproducible protein and peptide pools. From 556 spots identified by 2D gel electrophoresis, 66 differentially expressed post-translationally modified plasma proteins were identified in the leukemic subgroup only. This protein group was rich in complement components, acute-phase reactants and coagulation factors. Low molecular weight peptides corresponding to abundant plasma proteins were identified. A candidate marker panel of host response (9 plasma proteins, 4 peptides, fungal polysaccharides (galactomannan, and cell wall components (β-D glucan were selected by statistical filtering for patients with leukemia as a primary underlying diagnosis. Quantitative measurements were developed to qualify the differential expression of the candidate host response proteins using selective reaction monitoring mass spectrometry assays, and then applied to a separate cohort of 57 patients with leukemia. In this verification cohort, a machine learning ensemble-based algorithm, generalized pathseeker (GPS produced a greater case classification accuracy than galactomannan (GM or host proteins alone. In conclusion, Integration of host response proteins with GM improves the diagnostic detection of probable IPA in patients

  4. Pattern recognition in pulmonary tuberculosis defined by high content peptide microarray chip analysis representing 61 proteins from M. tuberculosis.

    Directory of Open Access Journals (Sweden)

    Simani Gaseitsiwe

    Full Text Available BACKGROUND: Serum antibody-based target identification has been used to identify tumor-associated antigens (TAAs for development of anti-cancer vaccines. A similar approach can be helpful to identify biologically relevant and clinically meaningful targets in M. tuberculosis (MTB infection for diagnosis or TB vaccine development in clinically well defined populations. METHOD: We constructed a high-content peptide microarray with 61 M. tuberculosis proteins as linear 15 aa peptide stretches with 12 aa overlaps resulting in 7446 individual peptide epitopes. Antibody profiling was carried with serum from 34 individuals with active pulmonary TB and 35 healthy individuals in order to obtain an unbiased view of the MTB epitope pattern recognition pattern. Quality data extraction was performed, data sets were analyzed for significant differences and patterns predictive of TB+/-. FINDINGS: Three distinct patterns of IgG reactivity were identified: 89/7446 peptides were differentially recognized (in 34/34 TB+ patients and in 35/35 healthy individuals and are highly predictive of the division into TB+ and TB-, other targets were exclusively recognized in all patients with TB (e.g. sigmaF but not in any of the healthy individuals, and a third peptide set was recognized exclusively in healthy individuals (35/35 but no in TB+ patients. The segregation between TB+ and TB- does not cluster into specific recognition of distinct MTB proteins, but into specific peptide epitope 'hotspots' at different locations within the same protein. Antigen recognition pattern profiles in serum from TB+ patients from Armenia vs. patients recruited in Sweden showed that IgG-defined MTB epitopes are very similar in individuals with different genetic background. CONCLUSIONS: A uniform target MTB IgG-epitope recognition pattern exists in pulmonary tuberculosis. Unbiased, high-content peptide microarray chip-based testing of clinically well-defined populations allows to visualize

  5. The PDZ protein TIP-1 facilitates cell migration and pulmonary metastasis of human invasive breast cancer cells in athymic mice

    Energy Technology Data Exchange (ETDEWEB)

    Han, Miaojun [Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Yunnan (China); Graduate School, Chinese Academy of Sciences, Beijing (China); Department of Radiation Oncology, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States); Wang, Hailun [Department of Radiation Oncology, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States); Zhang, Hua-Tang [Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Yunnan (China); Han, Zhaozhong, E-mail: zhaozhong.han@vanderbilt.edu [Department of Radiation Oncology, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States); Department of Cancer Biology, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States); Vanderbilt-Ingram Cancer Center, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States)

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer This study has revealed novel oncogenic functions of TIP-1 in human invasive breast cancer. Black-Right-Pointing-Pointer Elevated TIP-1 expression levels in human breast cancers correlate to the disease prognosis. Black-Right-Pointing-Pointer TIP-1 knockdown suppressed the cell migration and pulmonary metastasis of human breast cancer cells. Black-Right-Pointing-Pointer TIP-1 knockdown suppressed the expression and functionality of motility-related genes. -- Abstract: Tax-interacting protein 1 (TIP-1, also known as Tax1bp3) inhibited proliferation of colon cancer cells through antagonizing the transcriptional activity of beta-catenin. However, in this study, elevated TIP-1 expression levels were detected in human invasive breast cancers. Studies with two human invasive breast cancer cell lines indicated that RNAi-mediated TIP-1 knockdown suppressed the cell adhesion, proliferation, migration and invasion in vitro, and inhibited tumor growth in mammary fat pads and pulmonary metastasis in athymic mice. Biochemical studies showed that TIP-1 knockdown had moderate and differential effects on the beta-catenin-regulated gene expression, but remarkably down regulated the genes for cell adhesion and motility in breast cancer cells. The decreased expression of integrins and paxillin was accompanied with reduced cell adhesion and focal adhesion formation on fibronectin-coated surface. In conclusion, this study revealed a novel oncogenic function of TIP-1 suggesting that TIP-1 holds potential as a prognostic biomarker and a therapeutic target in the treatment of human invasive breast cancers.

  6. Surfactants in the environment.

    Science.gov (United States)

    Ivanković, Tomislav; Hrenović, Jasna

    2010-03-01

    Surfactants are a diverse group of chemicals that are best known for their wide use in detergents and other cleaning products. After use, residual surfactants are discharged into sewage systems or directly into surface waters, and most of them end up dispersed in different environmental compartments such as soil, water or sediment. The toxic effects of surfactants on various aquatic organisms are well known. In general, surfactants are present in the environment at levels below toxicity and in Croatia below the national limit. Most surfactants are readily biodegradable and their amount is greatly reduced with secondary treatment in wastewater treatment plants. The highest concern is the release of untreated wastewater or wastewater that has undergone primary treatment alone. The discharge of wastewater polluted with massive quantities of surfactants could have serious effects on the ecosystem. Future studies of surfactant toxicities and biodegradation are necessary to withdraw highly toxic and non-biodegradable compounds from commercial use and replace them with more environmentally friendly ones.