Sample records for airway surfactant protein

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

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    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.

  2. Surfactant proteins SP-B and SP-C and their precursors in bronchoalveolar lavages from children with acute and chronic inflammatory airway disease

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    Winter Tobias


    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.

  3. Computational modeling of unsteady surfactant-laden liquid plug propagation in neonatal airways (United States)

    Olgac, Ufuk; Muradoglu, Metin


    Surfactant-free and surfactant-laden liquid plug propagation in neonatal airways in various generations representing the upper and lower airways are investigated computationally using a finite-difference/front-tracking method. Emphasis is placed on the unsteady surfactant-laden plug propagation as a model for Surfactant Replacement Therapy (SRT) and airway reopening. The numerical method is designed to solve the evolution equations of the interfacial and bulk surfactant concentrations coupled with the incompressible Navier-Stokes equations. Available experimental data for surfactant Survanta are used to relate surface tension coefficient to surfactant concentration at the interface. It is found that, for the surfactant-free case, the trailing film thickness is in good agreement with Taylor's law for plugs with plug length greater than the airway width. Mechanical stresses that could be injurious to epithelial cells such as pressure and shear stress and their gradients are maximized on the front and rear menisci with increasing magnitudes in the lower generations. These mechanical stresses, especially pressure and pressure gradient, are diminished with the introduction of surfactants. Surfactant is absorbed onto the trailing film and thickens it, eventually leading to either plug rupture or, if totally consumed prior to rupture, to steadily propagating plug. In the upper airways, initially small plugs rupture rapidly and plugs with comparable initial plug length with the airway width persist and propagate steadily. For a more effective SRT treatment, we recommend utilization of plugs with initial plug length greater than the airway width. Increasing surfactant strength or increasing the initially instilled surfactant concentration is found to be ineffective.

  4. Pulmonary surfactant in the airway physiology: a direct relaxing effect on the smooth muscle. (United States)

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


    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.

  5. Cationic versus anionic surfactant in tuning the structure and interaction of nanoparticle, protein, and surfactant complexes. (United States)

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


    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.

  6. Surfactant protein D is proatherogenic in mice

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


    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...

  7. Biophysical inhibition of pulmonary surfactant function by polymeric nanoparticles: role of surfactant protein B and C. (United States)

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


    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.

  8. Molecular dynamics of surfactant protein C

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    Ramírez, Eunice; Santana, Alberto; Cruz, Anthony


    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...... are possible contributors to the pathogenesis of pulmonary alveolar proteinosis. Molecular dynamics simulations using the NAMD2 package were performed for systems containing from one to seven SP-C molecules to study their behavior in water. The results of our simulations show that unfolding of the protein...

  9. Structural study of surfactant-dependent interaction with protein

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    Mehan, Sumit; Aswal, Vinod K., E-mail: [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)


    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.

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

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


    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...... lavage and blood have indicated associations with a multitude of pulmonary inflammatory diseases. In addition, accumulating evidence in mouse models of infection and inflammation indicates that recombinant forms of the surfactant proteins are biologically active in vivo and may have therapeutic potential...... in controlling pulmonary inflammatory disease. The presence of the surfactant collectins, especially SP-D, in non-pulmonary tissues, such as the gastrointestinal tract and genital organs, suggest additional actions located to other mucosal surfaces. The aim of this review is to summarize studies on genetic...

  11. Porcine lung surfactant protein B gene (SFTPB)

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    Cirera Salicio, Susanna; Fredholm, Merete


    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...... bp in the region coding for the active protein. Northern analysis showed lung-specific expression of three different isoforms of the SFTPB transcript. The expression level for the SFTPB gene is low in 50 days-old fetus and it increases during lung development. Quantitative real-time polymerase chain...

  12. Different effects of surfactant proteins B and C - implications for development of synthetic surfactants. (United States)

    Curstedt, Tore; Johansson, Jan


    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.

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

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    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.

  14. In vitro surfactant and perfluorocarbon aerosol deposition in a neonatal physical model of the upper conducting airways.

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    Estibalitz Goikoetxea

    Full Text Available OBJECTIVE: Aerosol delivery holds potential to release surfactant or perfluorocarbon (PFC to the lungs of neonates with respiratory distress syndrome with minimal airway manipulation. Nevertheless, lung deposition in neonates tends to be very low due to extremely low lung volumes, narrow airways and high respiratory rates. In the present study, the feasibility of enhancing lung deposition by intracorporeal delivery of aerosols was investigated using a physical model of neonatal conducting airways. METHODS: The main characteristics of the surfactant and PFC aerosols produced by a nebulization system, including the distal air pressure and air flow rate, liquid flow rate and mass median aerodynamic diameter (MMAD, were measured at different driving pressures (4-7 bar. Then, a three-dimensional model of the upper conducting airways of a neonate was manufactured by rapid prototyping and a deposition study was conducted. RESULTS: The nebulization system produced relatively large amounts of aerosol ranging between 0.3±0.0 ml/min for surfactant at a driving pressure of 4 bar, and 2.0±0.1 ml/min for distilled water (H2Od at 6 bar, with MMADs between 2.61±0.1 µm for PFD at 7 bar and 10.18±0.4 µm for FC-75 at 6 bar. The deposition study showed that for surfactant and H2Od aerosols, the highest percentage of the aerosolized mass (∼65% was collected beyond the third generation of branching in the airway model. The use of this delivery system in combination with continuous positive airway pressure set at 5 cmH2O only increased total airway pressure by 1.59 cmH2O at the highest driving pressure (7 bar. CONCLUSION: This aerosol generating system has the potential to deliver relatively large amounts of surfactant and PFC beyond the third generation of branching in a neonatal airway model with minimal alteration of pre-set respiratory support.

  15. Surfactant protein D is proatherogenic in mice

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


    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...

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

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


    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...

  17. Key interactions of surfactants in therapeutic protein formulations: A review. (United States)

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


    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.

  18. Cell-specific modulation of surfactant proteins by ambroxol treatment. (United States)

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


    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.

  19. Structural characterisation of human proteinosis surfactant protein A

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


    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...

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

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


    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...

  1. Surfactant protein D in atopic dermatitis and psoriasis

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    Hohwy, Thomas; Otkjaer, Kristian; Madsen, Jens;


    The collectin surfactant protein-D (SP-D) shows antimicrobial and immuno-regulatory properties and has recently been detected in the basal layers of normal human skin. This molecule potentially plays an important role in inflammatory skin diseases and therefore SP-D content and location was exami......The collectin surfactant protein-D (SP-D) shows antimicrobial and immuno-regulatory properties and has recently been detected in the basal layers of normal human skin. This molecule potentially plays an important role in inflammatory skin diseases and therefore SP-D content and location...

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

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    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

  3. The importance of surfactant proteins-New aspects on macrophage phagocytosis. (United States)

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


    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.

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

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


    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...

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

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


    Surfactant protein D (SP-D) is an innate immune molecule that plays a protective role against lung infection, allergy, asthma and inflammation. In vivo experiments with murine models have shown that SP-D can protect against allergic challenge via a range of mechanisms including inhibition of alle...

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

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


    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 ...

  7. Immunohistochemical investigation of pulmonary surfactant-associated protein A in fire victims. (United States)

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


    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.

  8. The importance of administration of early surfactant and nasal continuous positive airway pressure in newborns with respiratory distress syndrome (United States)

    Ceylan, Abdullah; Gezer, Suat; Demir, Nihat; Tuncer, Oğuz; Peker, Erdal; Kırımi, Ercan


    Aim: Mechanical ventilation is an invasive method and causes to important problems in the respiratory tract and lung parenchyma. The objective of our study was to investigate if administration of early surfactant and nasal continuous positive airway pressure (nCPAP) was superior to delayed surfactant administration and mechanical ventilation. Material and Methods: The study was conducted in the Van 100th Year University, Medical Faculty Hospital, Neonatal Intensive Care Unit. One hundred and nine infants with respiratory distrss syndrome (RDS) with a gestational age of 32 weeks and/or below were included in the study. Surfactant was given to 61 infants in the delivery room or intensive care unit and subsequently nCPAP was administered. Surfactant was administered in 48 infants in the control group and mechanical ventilation was inititated subsequently. Informed consent was obtained from the relatives of all patients and ethics committee approval was also obtained (Approval number: 03.02.2011/15). Results: There was no statistically significant difference between the two groups in terms of gestational age, birth weight, gender, height and head circumference measurements (p>0.05). The mean hospitalization time in the patients in the study group was 24.4±17.8 days, whereas the mean time of nCPAP was 28.4 (4–120) hours. In the study group, intracranial hemorrhage was found with a rate of 27.85%, bronchopulmonary dysplasia was found with a rate of 4.91%, pneumothorax was found with a rate of 3.27%, necrotizing enterocolitis was found with a rate of 3.27%, patent ductus arteriosus was found with a rate of 16.39, sepsis was found with a rate of 22.95% and retinopathy of prematurity was found with a rate of 1.63%. No statistically significant difference was found between the study and control groups in terms of the rates of complications. During the follow-up period, 17 (27.86%) patients were lost. The length of stay on mechanical ventilation in the study group was

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

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


    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...

  10. Impact of a surfactant on the electroactivity of proteins at an aqueous-organogel microinterface array. (United States)

    O'Sullivan, Shane; Arrigan, Damien W M


    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.

  11. An enzyme-linked immunosorbent assay (ELISA) for quantification of mouse surfactant protein D (SP-D)

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    Hansen, Soren; Schmidt, Vivi; Steffensen, Maria Abildgaard;


    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...

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

    Directory of Open Access Journals (Sweden)

    Valery V. Novochadov


    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.

  13. Complexation between dodecyl sulfate surfactant and zein protein in solution. (United States)

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


    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.

  14. Tuning of protein-surfactant interaction to modify the resultant structure. (United States)

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


    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.

  15. Amphiphilic biopolymers (amphibiopols) as new surfactants for membrane protein solubilization (United States)

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


    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

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

    DEFF Research Database (Denmark)

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


    Surfactant protein D (SP-D) is a collectin believed to play an important role in innate immunity. SP-D is characterized by having a collagen-like domain and a carbohydrate recognition domain (CRD), which has a specific Ca2+-dependent specificity for saccharides and thus the ability to bind complex...... in a dose and Ca2+-dependent manner with a saccharide specificity similar to rat and human SP-D. The purified protein was used for the production of a monoclonal anti-pSP-D antibody. The antibody reacted specifically with pSP-D in the reduced and unreduced state when analysed by Western blotting...

  17. Surfactant protein D in the female genital tract

    DEFF Research Database (Denmark)

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


    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...

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

    Sarker, Muzaddid; Jackman, Donna; Booth, Valerie


    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.

  19. Method for 3D Airway Topology Extraction

    Directory of Open Access Journals (Sweden)

    Roman Grothausmann


    Full Text Available In lungs the number of conducting airway generations as well as bifurcation patterns varies across species and shows specific characteristics relating to illnesses or gene variations. A method to characterize the topology of the mouse airway tree using scanning laser optical tomography (SLOT tomograms is presented in this paper. It is used to test discrimination between two types of mice based on detected differences in their conducting airway pattern. Based on segmentations of the airways in these tomograms, the main spanning tree of the volume skeleton is computed. The resulting graph structure is used to distinguish between wild type and surfactant protein (SP-D deficient knock-out mice.

  20. Lung remodeling in aging surfactant protein D deficient mice. (United States)

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


    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

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

    Directory of Open Access Journals (Sweden)

    Russo Scott J


    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.

  2. Spontaneous surface self-assembly in protein-surfactant mixtures: interactions between hydrophobin and ethoxylated polysorbate surfactants. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Mi Young Yang


    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.

  4. Extracellular matrix proteins modulate asthmatic airway smooth muscle cell proliferation via an autocrine mechanism

    NARCIS (Netherlands)

    Johnson, Peter R A; Burgess, Janette K; Underwood, P Anne; Au, Wendy; Poniris, Maree H; Tamm, Michael; Ge, Qi; Roth, Michael; Black, Judith L


    BACKGROUND: Airway remodeling is a key feature of persistent asthma and includes alterations in the extracellular matrix protein profile around the airway smooth muscle (ASM) and hyperplasia of the ASM. We have previously shown that nonasthmatic ASM cells in culture produce a range of extracellular

  5. Molecular biological characterization of equine surfactant protein A. (United States)

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


    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.

  6. 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.


    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

  7. 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


    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...

  8. Bactericidal/Permeability-increasing protein fold-containing family member A1 in airway host protection and respiratory disease. (United States)

    Britto, Clemente J; Cohn, Lauren


    Bactericidal/permeability-increasing protein fold-containing family member A1 (BPIFA1), formerly known as SPLUNC1, is one of the most abundant proteins in respiratory secretions and has been identified with increasing frequency in studies of pulmonary disease. Its expression is largely restricted to the respiratory tract, being highly concentrated in the upper airways and proximal trachea. BPIFA1 is highly responsive to airborne pathogens, allergens, and irritants. BPIFA1 actively participates in host protection through antimicrobial, surfactant, airway surface liquid regulation, and immunomodulatory properties. Its expression is modulated in multiple lung diseases, including cystic fibrosis, chronic obstructive pulmonary disease, respiratory malignancies, and idiopathic pulmonary fibrosis. However, the role of BPIFA1 in pulmonary pathogenesis remains to be elucidated. This review highlights the versatile properties of BPIFA1 in antimicrobial protection and its roles as a sensor of environmental exposure and regulator of immune cell function. A greater understanding of the contribution of BPIFA1 to disease pathogenesis and activity may clarify if BPIFA1 is a biomarker and potential drug target in pulmonary disease.

  9. "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.

  10. Role of lung surfactant in respiratory disease: current knowledge in large animal medicine. (United States)

    Christmann, U; Buechner-Maxwell, V A; Witonsky, S G; Hite, R D


    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.

  11. Untapped therapeutic potential of surfactant proteins: is there a case for recombinant SP-D supplementation in neonatal lung disease? (United States)

    Clark, Howard W


    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.

  12. Signaling and regulation of G protein-coupled receptors in airway smooth muscle

    Directory of Open Access Journals (Sweden)

    Penn Raymond B


    Full Text Available Abstract Signaling through G protein-coupled receptors (GPCRs mediates numerous airway smooth muscle (ASM functions including contraction, growth, and "synthetic" functions that orchestrate airway inflammation and promote remodeling of airway architecture. In this review we provide a comprehensive overview of the GPCRs that have been identified in ASM cells, and discuss the extent to which signaling via these GPCRs has been characterized and linked to distinct ASM functions. In addition, we examine the role of GPCR signaling and its regulation in asthma and asthma treatment, and suggest an integrative model whereby an imbalance of GPCR-derived signals in ASM cells contributes to the asthmatic state.

  13. Biomarkers in Airway Diseases

    Directory of Open Access Journals (Sweden)

    Janice M Leung


    Full Text Available The inherent limitations of spirometry and clinical history have prompted clinicians and scientists to search for surrogate markers of airway diseases. Although few biomarkers have been widely accepted into the clinical armamentarium, the authors explore three sources of biomarkers that have shown promise as indicators of disease severity and treatment response. In asthma, exhaled nitric oxide measurements can predict steroid responsiveness and sputum eosinophil counts have been used to titrate anti-inflammatory therapies. In chronic obstructive pulmonary disease, inflammatory plasma biomarkers, such as fibrinogen, club cell secretory protein-16 and surfactant protein D, can denote greater severity and predict the risk of exacerbations. While the multitude of disease phenotypes in respiratory medicine make biomarker development especially challenging, these three may soon play key roles in the diagnosis and management of airway diseases.

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


    Macáková, Lubica


    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...

  15. Interactions between Surfactants in Solution and Electrospun Protein Fibers: Effects on Release Behavior and Fiber Properties. (United States)

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


    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.

  16. 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;


    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...

  17. Study of the interactions between lysozyme and a fully-fluorinated surfactant in aqueous solution at different surfactant-protein ratios. (United States)

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


    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.

  18. Natural history of five children with surfactant protein C mutations and interstitial lung disease. (United States)

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


    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.

  19. Characteristics of sugar surfactants in stabilizing proteins during freeze-thawing and freeze-drying. (United States)

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


    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.

  20. Comparative evaluation of heterologous production systems for recombinant pulmonary surfactant protein D

    Directory of Open Access Journals (Sweden)

    Daniela eSalgado


    Full Text Available Commercial surfactant products derived from animal lungs are used for the treatment of respiratory diseases in premature neonates. These products contain lipids and the hydrophobic surfactant proteins B and C, which help to lower the surface tension in the lungs. Surfactant products are less effective when pulmonary diseases involve inflammatory complications because two hydrophilic surfactant proteins (A and D are lost during the extraction process, yet surfactant protein D (SP-D is a component of the innate immune system that helps to reduce lung inflammation. The performance of surfactant products could therefore be improved by supplementing them with an additional source of SP-D. Recombinant SP-D is produced in mammalian cells and bacteria (Escherichia coli, and also experimentally in the yeast Pichia pastoris. Mammalian cells produce full-size SP-D, but the yields are low and the cost of production is high. In contrast, bacteria produce a truncated form of SP-D, which is active in vitro and in vivo, and higher yields can be achieved at a lower cost. We compare the efficiency of production of recombinant SP-D in terms of the total yields achieved in each system and the amount of SP-D needed to meet the global demand for the treatment of pulmonary diseases, using respiratory distress syndrome as a case study.

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

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    Raymond Maikokera


    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.

  2. On relationships between surfactant type and globular proteins interactions in solution. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Anna Tarocco


    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.

  4. Electrophoretic and spectroscopic characterization of the protein patterns formed in different surfactant solutions. (United States)

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


    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.

  5. The structure of latherin, a surfactant allergen protein from horse sweat and saliva. (United States)

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


    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.

  6. 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


    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

  7. 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

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


    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

  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


    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. 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.


    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...

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


    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.

  12. 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)


    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

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

    DEFF Research Database (Denmark)

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


    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...

  14. 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;


    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 ...

  15. 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


    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...

  16. 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


    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...

  17. 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;


    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....

  18. 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


    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...

  19. Protein-nanoparticle interactions evaluation by immunomethods: Surfactants can disturb quantitative determinations. (United States)

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


    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.

  20. Interaction of Moringa oleifera seed protein with a mineral surface and the influence of surfactants. (United States)

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


    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.

  1. 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


    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.

  2. Metformin reduces airway inflammation and remodeling via activation of AMP-activated protein kinase. (United States)

    Park, Chan Sun; Bang, Bo-Ram; Kwon, Hyouk-Soo; Moon, Keun-Ai; Kim, Tae-Bum; Lee, Ki-Young; Moon, Hee-Bom; Cho, You Sook


    Recent reports have suggested that metformin has anti-inflammatory and anti-tissue remodeling properties. We investigated the potential effect of metformin on airway inflammation and remodeling in asthma. The effect of metformin treatment on airway inflammation and pivotal characteristics of airway remodeling were examined in a murine model of chronic asthma generated by repetitive challenges with ovalbumin and fungal-associated allergenic protease. To investigate the underlying mechanism of metformin, oxidative stress levels and AMP-activated protein kinase (AMPK) activation were assessed. To further elucidate the role of AMPK, we examined the effect of 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR) as a specific activator of AMPK and employed AMPKα1-deficient mice as an asthma model. The role of metformin and AMPK in tissue fibrosis was evaluated using a bleomycin-induced acute lung injury model and in vitro experiments with cultured fibroblasts. Metformin suppressed eosinophilic inflammation and significantly reduced peribronchial fibrosis, smooth muscle layer thickness, and mucin secretion. Enhanced AMPK activation and decreased oxidative stress in lungs was found in metformin-treated asthmatic mice. Similar results were observed in the AICAR-treated group. In addition, the enhanced airway inflammation and fibrosis in heterozygous AMPKα1-deficient mice were induced by both allergen and bleomycin challenges. Fibronectin and collagen expression was diminished by metformin through AMPKα1 activation in cultured fibroblasts. Therefore metformin reduced both airway inflammation and remodeling at least partially through the induction of AMPK activation and decreased oxidative stress. These data provide insight into the beneficial role of metformin as a novel therapeutic drug for chronic asthma.

  3. Fluorescent Ensemble Based on Bispyrene Fluorophore and Surfactant Assemblies: Sensing and Discriminating Proteins in Aqueous Solution. (United States)

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


    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.

  4. Proteomic analysis of pure human airway gland mucus reveals a large component of protective proteins.

    Directory of Open Access Journals (Sweden)

    Nam Soo Joo

    Full Text Available Airway submucosal glands contribute to innate immunity and protect the lungs by secreting mucus, which is required for mucociliary clearance and which also contains antimicrobial, anti-inflammatory, anti-proteolytic and anti-oxidant proteins. We stimulated glands in tracheal trimmings from three lung donors and collected droplets of uncontaminated mucus as they formed at the gland orifices under an oil layer. We analyzed the mucus using liquid chromatography-tandem mass spectrometry (LC-MS/MS. Analysis identified 5486 peptides and 441 proteins from across the 3 samples (269-319 proteins per subject. We focused on 269 proteins common to at least 2 0f 3 subjects, of which 102 (38% had protective or innate immunity functions. While many of these have long been known to play such roles, for many others their cellular protective functions have only recently been appreciated in addition to their well-studied biologic functions (e.g. annexins, apolipoproteins, gelsolin, hemoglobin, histones, keratins, and lumican. A minority of the identified proteins are known to be secreted via conventional exocytosis, suggesting that glandular secretion occurs via multiple mechanisms. Two of the observed protective proteins, major vault protein and prohibitin, have not been observed in fluid from human epithelial cultures or in fluid from nasal or bronchoalveolar lavage. Further proteomic analysis of pure gland mucus may help clarify how healthy airways maintain a sterile environment.

  5. Directed differentiation of airway epithelial cells of human bone marrow mesenchymal stem cells. (United States)

    Li, Jian-Dong


    The ability to generate lung and airway epithelial cells from human bone marrow mesenchymal stem cells (hBMSCs) would have applications in regenerative medicine, modeling of lung disease, drug screening, and studies of human lung development. In this research, hBMSCs were cultured in specialized airway epithelial cell growth media for differentiation of airway epithelial cells, including keratinocyte growth factor transferrin, bovine pituitary extract, epinephrine, triiodothyronine and retinoic acid. The surfactant protein C, a specific marker of type II pneumocytes, and its corresponding protein were demonstrated by immunofluorescence and western blotting after differentiation of airway epithelial cells, respectively. These cells were then transferred into an induced acute lung injury model. The results showed that the hBMSCs could induce differentiation in airway epithelial cells under the special conditions of the medium, the result for surfactant protein C was positive in differentiated airway epithelial cells using immunofluorescence and western blotting, and these cells were successfully colonized in the injured lung airway. In conclusion, our research shows that a population of airway epithelial cells can be specifically generated from hBMSCs and that induced cells may be allowed to participate in tissue repair.

  6. Structure and dynamics of a protein-surfactant assembly studied by ion-mobility mass spectrometry and molecular dynamics simulations. (United States)

    Borysik, Antoni J


    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.

  7. 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


    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...... were used to associate genetic variation to SP-D, respiratory distress (RD), oxygen requirement, and respiratory support. RESULTS: The 5'-upstream SFTPD SNP rs1923534 and the 3 structural SNPs rs721917, rs2243639, and rs3088308 were associated with the SP-D level. The same SNPs were associated with RD......, a requirement for supplemental oxygen, and a requirement for respiratory support. Haplotype analyses identified 3 haplotypes that included the minor alleles of rs1923534, rs721917, and rs3088308 that exhibited highly significant associations with decreased SP-D levels and decreased ORs for RD, oxygen...

  8. Do cell junction protein mutations cause an airway phenotype in mice or humans? (United States)

    Chang, Eugene H; Pezzulo, Alejandro A; Zabner, Joseph


    Cell junction proteins connect epithelial cells to each other and to the basement membrane. Genetic mutations of these proteins can cause alterations in some epithelia leading to varied phenotypes such as deafness, renal disease, skin disorders, and cancer. This review examines if genetic mutations in these proteins affect the function of lung airway epithelia. We review cell junction proteins with examples of disease mutation phenotypes in humans and in mouse knockout models. We also review which of these genes are expressed in airway epithelium by microarray expression profiling and immunocytochemistry. Last, we present a comprehensive literature review to find the lung phenotype when cell junction and adhesion genes are mutated or subject to targeted deletion. We found that in murine models, targeted deletion of cell junction and adhesion genes rarely result in a lung phenotype. Moreover, mutations in these genes in humans have no obvious lung phenotype. Our research suggests that simply because a cell junction or adhesion protein is expressed in an organ does not imply that it will exhibit a drastic phenotype when mutated. One explanation is that because a functioning lung is critical to survival, redundancy in the system is expected. Therefore mutations in a single gene might be compensated by a related function of a similar gene product. Further studies in human and animal models will help us understand the overlap in the function of cell junction gene products. Finally, it is possible that the human lung phenotype is subtle and has not yet been described.

  9. Application of polyhydroxyalkanoate binding protein PhaP as a bio-surfactant. (United States)

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


    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.

  10. Surfactant protein (SP)-A and SP-D as antimicrobial and immunotherapeutic agents. (United States)

    Awasthi, Shanjana


    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.

  11. Interleukin-12 suppresses filaria-induced pulmonary eosinophilia, deposition of major basic protein and airway hyperresponsiveness. (United States)

    Mehlotra, R K; Hall, L R; Higgins, A W; Dreshaj, I A; Haxhiu, M A; Kazura, J W; Pearlman, E


    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.

  12. Eosinophil cationic protein stimulates and major basic protein inhibits airway mucus secretion

    DEFF Research Database (Denmark)

    Lundgren, J D; Davey, R T; Lundgren, B


    Possible roles of eosinophil (EO) products in modulating the release of mucus from airway explants were investigated. Cell- and membrane-free lysates from purified human EOs (1 to 20 x 10(5)) caused a dose-dependent release of respiratory glycoconjugates (RGC) from cultured feline tracheal explants...... chromatography. ECP (0.025 to 25 micrograms/ml) caused a dose-dependent increase in RGC release from both feline and human airway explants and also stimulated the release of the serous cell-marker, lactoferrin, from human bronchial explants. EO-derived neurotoxin (0.025 to 50 micrograms/ml) failed to affect RGC...... release, whereas MBP (50 micrograms/ml) significantly inhibited RGC release from feline explants. Thus, ECP stimulates RGC and lactoferrin release from airway explants, whereas MBP inhibits RGC release....

  13. Biophysical mimicry of lung surfactant protein B by random nylon-3 copolymers. (United States)

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


    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.

  14. Factors affecting protein transfer into surfactant-isooctane solution: a case study of extraction behavior of chemically modified cytochrome c. (United States)

    Ono, T; Goto, M


    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.

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

    DEFF Research Database (Denmark)

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


    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...

  16. 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.

  17. Effect of silk protein surfactant on silk degumming and its properties. (United States)

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


    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.

  18. 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


    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....

  19. Extra-cellular matrix proteins induce matrix metalloproteinase-1 (MMP-1 activity and increase airway smooth muscle contraction in asthma.

    Directory of Open Access Journals (Sweden)

    Natasha K Rogers

    Full Text Available Airway remodelling describes the histopathological changes leading to fixed airway obstruction in patients with asthma and includes extra-cellular matrix (ECM deposition. Matrix metalloproteinase-1 (MMP-1 is present in remodelled airways but its relationship with ECM proteins and the resulting functional consequences are unknown. We used airway smooth muscle cells (ASM and bronchial biopsies from control donors and patients with asthma to examine the regulation of MMP-1 by ECM in ASM cells and the effect of MMP-1 on ASM contraction. Collagen-I and tenascin-C induced MMP-1 protein expression, which for tenascin-C, was greater in asthma derived ASM cells. Tenascin-C induced MMP-1 expression was dependent on ERK1/2, JNK and p38 MAPK activation and attenuated by function blocking antibodies against the β1 and β3 integrin subunits. Tenascin-C and MMP-1 were not expressed in normal airways but co-localised in the ASM bundles and reticular basement membrane of patients with asthma. Further, ECM from asthma derived ASM cells stimulated MMP-1 expression to a greater degree than ECM from normal ASM. Bradykinin induced contraction of ASM cells seeded in 3D collagen gels was reduced by the MMP inhibitor ilomastat and by siRNA knockdown of MMP-1. In summary, the induction of MMP-1 in ASM cells by tenascin-C occurs in part via integrin mediated MAPK signalling. MMP-1 and tenascin-C are co-localised in the smooth muscle bundles of patients with asthma where this interaction may contribute to enhanced airway contraction. Our findings suggest that ECM changes in airway remodelling via MMP-1 could contribute to an environment promoting greater airway narrowing in response to broncho-constrictor stimuli and worsening asthma symptoms.

  20. Biosurfactants and surfactants interacting with membranes and proteins: Same but different? (United States)

    Otzen, Daniel E


    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.

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

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


    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.

  2. Nonlinear Surface Dilatational Rheology and Foaming Behavior of Protein and Protein Fibrillar Aggregates in the Presence of Natural Surfactant. (United States)

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


    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.

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

    DEFF Research Database (Denmark)

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


    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...... polymorphisms. In conclusion, the functional rs1130866, rs2077079 and rs3024791 polymorphisms in the SP-B gene are not associated with reduced lung function or risk of COPD, making it unlikely that these variants will be useful in personalised medicine....

  4. Contribution of protein kinase C to passively sensitized human airway smooth muscle cells proliferation

    Institute of Scientific and Technical Information of China (English)

    许淑云; 徐永健; 张珍祥; 倪望; 陈士新


    Background Airway smooth muscle proliferation plays an important role in airway remodeling in asthma. But little is known about the intracellular signal pathway in the airway smooth muscle cell proliferation in asthma. The objective of this paper is to investigate the contribution of protein kinase C (PKC) and its alpha isoform to passively sensitized human airway smooth muscle cells (HASMCs) proliferation.Methods HASMCs in culture were passively sensitized with 10% serum from asthmatic patients, with non-asthmatic human serum treated HASMCs used as the control. The proliferation of HASMCs was examined by cell cycle analysis, 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyltetrazoliumbromide (MTT) colorimetric assay and proliferating cell nuclear antigen (PCNA) immunofluorescence staining. The effect of PKC agonist phorbol 12-myristate 13-acetate (PMA) and PKC inhibitor Ro-31-8220 on the proliferation of HASMCs exposed to human asthmatic serum and non-asthmatic control serum was also examined by the same methods. The protein and mRNA expression of PKC-α in passively sensitized HASMCs were detected by immunofluorescence staining and reverse transcription-polymerase chain reaction.Results The percentage of S phase, absorbance (value A) and the positive percentage of PCNA protein expression in HASMCs passively sensitized with asthmatic serum were (16.30±2.68)%, 0.430±0.060 and (63.4±7.4)% respectively, which were significantly increased compared with HASMCs treated with control serum [(10.01±1.38)%, 0.328±0.034 and (37.2±4.8)%, respectively] (P<0.05). After HASMCs were passively sensitized with asthmatic serum, they were treated with PMA, the percentage of S phase, value A and the positive percentage of PCNA protein expression were (20.33±3.39)%, 0.542±0.065 and (76.0±8.7)% respectively, which were significantly increased compared with asthmatic serum sensitized HASMCs without PMA(P<0.05). After HASMCs passively sensitized with asthmatic serum were treated with

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

    DEFF Research Database (Denmark)

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


    The surfactant, pulmonary-associated protein C (SFTPC) is a peptide secreted by the alveolar type II pneumocytes of the lung. We have characterized the porcine SFTPC gene at genomic, transcriptional, and protein levels. The porcine SFTPC is a single-copy gene on pig chromosome 14. Two transcripts...... were found in a newborn pig lung cDNA library: a full-length clone and a clone missing exon 5. cDNA sequence comparison revealed four synonymous and two nonsynonymous substitutions and in-frame insertions at the beginning of exon 5. Comparison of the SFTPC coding region between several mammals showed......-regulated in necrotic lungs of pigs infected with Actinobacillus pleuropneumoniae. Additionally, the protein levels were also decreased or absent in the necrotic tissue....

  6. Surfactant protein A2 mutations associated with pulmonary fibrosis lead to protein instability and endoplasmic reticulum stress. (United States)

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


    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.

  7. Macrophage adaptation in airway inflammatory resolution

    Directory of Open Access Journals (Sweden)

    Manminder Kaur


    Full Text Available Bacterial and viral infections (exacerbations are particularly problematic in those with underlying respiratory disease, including post-viral infection, asthma, chronic obstructive pulmonary disease and pulmonary fibrosis. Patients experiencing exacerbations tend to be at the more severe end of the disease spectrum and are often difficult to treat. Most of the unmet medical need remains in this patient group. Airway macrophages are one of the first cell populations to encounter airborne pathogens and, in health, exist in a state of reduced responsiveness due to interactions with the respiratory epithelium and specific factors found in the airway lumen. Granulocyte–macrophage colony-stimulating factor, interleukin-10, transforming growth factor-β, surfactant proteins and signalling via the CD200 receptor, for example, all raise the threshold above which airway macrophages can be activated. We highlight that following severe respiratory inflammation, the airspace microenvironment does not automatically re-set to baseline and may leave airway macrophages more restrained than they were at the outset. This excessive restraint is mediated in part by the clearance of apoptotic cells and components of extracellular matrix. This implies that one strategy to combat respiratory exacerbations would be to retune airway macrophage responsiveness to allow earlier bacterial recognition.

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

    Directory of Open Access Journals (Sweden)

    Julien Perino


    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.

  9. 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;


    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...

  10. 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


    ), 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...

  11. 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


    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...

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


    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.

  13. 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.

  14. Chemotherapeutic treatment reduces circulating levels of surfactant protein-D in children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Rathe, Mathias; Sorensen, Grith L; Wehner, Peder S;


    BACKGROUND: Surfactant protein D (SP-D) is a host defense molecule of the innate immune system that enhances pathogen clearance and modulates inflammatory responses. We hypothesized that circulating SP-D levels are associated with chemotherapy-induced mucositis and infectious morbidity in children...... with acute lymphoblastic leukemia (ALL). PROCEDURE: In a prospective study, 43 children receiving treatment for ALL were monitored for mucosal toxicity from diagnosis through the induction phase of treatment. Serial blood draws were taken to determine the levels of SP-D, interleukin-6 (IL-6), C......-reactive protein, and white blood cells. Data on fever, antibiotics, and bacteremia were collected. Baseline levels of circulating SP-D were compared with healthy controls. RESULTS: Baseline values of circulating SP-D were similar to levels in healthy controls (median: 829 ng/ml vs. 657 ng/ml, respectively, P > 0...

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

    Directory of Open Access Journals (Sweden)

    Samukawa Takuya


    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.

  16. 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;


    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...

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

    Directory of Open Access Journals (Sweden)

    Zhou Bihong


    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

  18. 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)


    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.)

  19. 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


    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

  20. Protein kinase C epsilon is important in modulating organic-dust-induced airway inflammation. (United States)

    Poole, Jill A; Romberger, Debra J; Bauer, Chris; Gleason, Angela M; Sisson, Joseph H; Oldenburg, Peter J; West, William W; Wyatt, Todd A


    Organic dust samples from swine confinement facilities elicit pro-inflammatory cytokine/chemokine release from bronchial epithelial cells and monocytes, dependent, in part, upon dust-induced activation of the protein kinase C (PKC) isoform, PKCε. PKCε is also rapidly activated in murine tracheal epithelial cells following in vivo organic dust challenges, yet the functional role of PKCε in modulating dust-induced airway inflammatory outcomes is not defined. Utilizing an established intranasal inhalation animal model, experiments investigated the biologic and physiologic responses following organic dust extract (ODE) treatments in wild-type (WT) and PKCε knock-out (KO) mice. We found that neutrophil influx increased more than twofold in PKCε KO mice following both a one-time challenge and 3 weeks of daily challenges with ODE as compared with WT mice. Lung pathology revealed increased bronchiolar and alveolar inflammation, lymphoid aggregates, and T cell influx in ODE-treated PKCε KO mice. Airway hyperresponsiveness to methacholine increased in PKCε KO + ODE to a greater magnitude than WT + ODE animals. There were no significant differences in cytokine/chemokine release elicited by ODE treatment between groups. However, ODE-induced nitric oxide (NO) production differed in that ODE exposure increased nitrate levels in WT mice but not in PKCε KO mice. Moreover, ODE failed to upregulate NO from ex vivo stimulated PKCε KO lung macrophages. Collectively, these studies demonstrate that PKCε-deficient mice were hypersensitive to organic dust exposure and suggest that PKCε is important in the normative lung inflammatory response to ODE. Dampening of ODE-induced NO may contribute to these enhanced inflammatory findings.

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

    Directory of Open Access Journals (Sweden)

    Guttentag Susan


    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.

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


    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.

  3. 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


    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.

  4. 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


    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.

  5. 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;


    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...

  6. Pulmonary surfactant and lung transplantation

    NARCIS (Netherlands)

    Erasmus, Michiel Elardus


    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

  7. 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;


    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...

  8. 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;


    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....

  9. Airway epithelial inflammation-induced endoplasmic reticulum Ca2+ store expansion is mediated by X-box binding protein-1. (United States)

    Martino, Mary E B; Olsen, John C; Fulcher, Nanette B; Wolfgang, Matthew C; O'Neal, Wanda K; Ribeiro, Carla M P


    Inflamed cystic fibrosis (CF) human bronchial epithelia (HBE), or normal HBE exposed to supernatant from mucopurulent material (SMM) from CF airways, exhibit endoplasmic reticulum (ER)/Ca(2+) store expansion and amplified Ca(2+)-mediated inflammation. HBE inflammation triggers an unfolded protein response (UPR) coupled to mRNA splicing of X-box binding protein-1 (XBP-1). Because spliced XBP-1 (XBP-1s) promotes ER expansion in other cellular models, we hypothesized that XBP-1s is responsible for the ER/Ca(2+) store expansion in inflamed HBE. XBP-1s was increased in freshly isolated infected/inflamed CF in comparison with normal HBE. The link between airway epithelial inflammation, XBP-1s, and ER/Ca(2+) store expansion was then addressed in murine airways challenged with phosphate-buffered saline or Pseudomonas aeruginosa. P. aeruginosa-challenged mice exhibited airway epithelial ER/Ca(2+) store expansion, which correlated with airway inflammation. P. aeruginosa-induced airway inflammation triggered XBP-1s in ER stress-activated indicator (ERAI) mice. To evaluate the functional role of XBP-1s in airway inflammation linked to ER/Ca(2+) store expansion, control, XBP-1s, or dominant negative XBP-1 (DN-XBP-1) stably expressing 16HBE14o(-) cell lines were used. Studies with cells transfected with an unfolded protein response element (UPRE) luciferase reporter plasmid confirmed that the UPRE was activated or inhibited by expression of XBP-1s or DN-XBP-1, respectively. Expression of XBP-1s induced ER/Ca(2+) store expansion and potentiated bradykinin-increased interleukin (IL)-8 secretion, whereas expression of DN-XBP-1 inhibited bradykinin-dependent IL-8 secretion. In addition, expression of DN-XBP-1 blunted SMM-induced ER/Ca(2+) store expansion and SMM-induced IL-8 secretion. These findings suggest that, in inflamed HBE, XBP-1s is responsible for the ER/Ca(2+) store expansion that confers amplification of Ca(2+)-dependent inflammatory responses.

  10. Involvement of eicosanoids and surfactant protein D in extrinsic allergic alveolitis. (United States)

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


    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.

  11. 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;


    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....... 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...

  12. Interaction of surfactant protein A with the intermediate filaments desmin and vimentin. (United States)

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


    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.

  13. Effect of surfactants on Ra-sHSPI - A small heat shock protein from the cattle tick Rhipicephalus annulatus (United States)

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


    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.

  14. Klebsiella pneumoniae outer membrane protein A is required to prevent the activation of airway epithelial cells. (United States)

    March, Catalina; Moranta, David; Regueiro, Verónica; Llobet, Enrique; Tomás, Anna; Garmendia, Junkal; Bengoechea, José A


    Outer membrane protein A (OmpA) is a class of proteins highly conserved among the Enterobacteriaceae family and throughout evolution. Klebsiella pneumoniae is a capsulated gram-negative pathogen. It is an important cause of community-acquired and nosocomial pneumonia. Evidence indicates that K. pneumoniae infections are characterized by a lack of an early inflammatory response. Data from our laboratory indicate that K. pneumoniae CPS helps to suppress the host inflammatory response. However, it is unknown whether K. pneumoniae employs additional factors to modulate host inflammatory responses. Here, we report that K. pneumoniae OmpA is important for immune evasion in vitro and in vivo. Infection of A549 and normal human bronchial cells with 52OmpA2, an ompA mutant, increased the levels of IL-8. 52145-Δwca(K2)ompA, which does not express CPS and ompA, induced the highest levels of IL-8. Both mutants could be complemented. In vivo, 52OmpA2 induced higher levels of tnfα, kc, and il6 than the wild type. ompA mutants activated NF-κB, and the phosphorylation of p38, p44/42, and JNK MAPKs and IL-8 induction was via NF-κB-dependent and p38- and p44/42-dependent pathways. 52OmpA2 engaged TLR2 and -4 to activate NF-κB, whereas 52145-Δwca(K2)ompA activated not only TLR2 and TLR4 but also NOD1. Finally, we demonstrate that the ompA mutant is attenuated in the pneumonia mouse model. The results of this study indicate that K. pneumoniae OmpA contributes to attenuate airway cell responses. This may facilitate pathogen survival in the hostile environment of the lung.

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


    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.

  16. Surfactant protein A regulates IgG-mediated phagocytosis in inflammatory neutrophils. (United States)

    Wofford, Jessica A; Wright, Jo Rae


    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.

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

    Directory of Open Access Journals (Sweden)

    Annapurna eNayak


    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.

  18. 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


    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.

  19. Barrier or carrier? Pulmonary surfactant and drug delivery. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Bracken Michael B


    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.

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

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    Erpenbeck Veit J


    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

  2. Surfactant protein A expression in human normal and neoplastic breast epithelium. (United States)

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


    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.

  3. [Surfactant protein and thyroid transcription factor 1 in pleuro-pulmonary neoplasia. Immunohistochemical study]. (United States)

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


    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.

  4. Microfibrillar-associated protein 4 modulates airway smooth muscle cell phenotype in experimental asthma

    DEFF Research Database (Denmark)

    Pilecki, Bartosz; Schlosser, Anders; Wulf-Johansson, Helle


    . In the current study we investigated the role of MFAP4 in experimental allergic asthma. METHODS: MFAP4-deficient mice were subjected to alum/ovalbumin and house dust mite induced models of allergic airway disease. In addition, human healthy and asthmatic primary bronchial smooth muscle cell cultures were used...... to evaluate MFAP4-dependent airway smooth muscle responses. RESULTS: MFAP4 deficiency attenuated classical hallmarks of asthma, such as eosinophilic inflammation, eotaxin production, airway remodelling and hyperresponsiveness. In wild-type mice, serum MFAP4 was increased after disease development...... and correlated with local eotaxin levels. MFAP4 was expressed in human bronchial smooth muscle cells and its expression was upregulated in asthmatic cells. Regarding the underlying mechanism, we showed that MFAP4 interacted with integrin αvβ5 and promoted asthmatic bronchial smooth muscle cell proliferation...

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

  6. Exploring the affinity binding of alkylmaltoside surfactants to bovine serum albumin and their effect on the protein stability: A spectroscopic approach. (United States)

    Hierrezuelo, J M; Carnero Ruiz, C


    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.

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

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    Chang-Jiang Guo


    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.

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

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    Sorensen Grith L


    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.

  9. CD4+ T cells enhance the unloaded shortening velocity of airway smooth muscle by altering the contractile protein expression. (United States)

    Matusovsky, Oleg S; Nakada, Emily M; Kachmar, Linda; Fixman, Elizabeth D; Lauzon, Anne-Marie


    Abundant data indicate that pathogenesis in allergic airways disease is orchestrated by an aberrant T-helper 2 (Th2) inflammatory response. CD4(+) T cells have been localized to airway smooth muscle (ASM) in both human asthmatics and in rodent models of allergic airways disease, where they have been implicated in proliferative responses of ASM. Whether CD4(+) T cells also alter ASM contractility has not been addressed. We established an in vitro system to assess the ability of antigen-stimulated CD4(+) T cells to modify contractile responses of the Brown Norway rat trachealis muscle. Our data demonstrated that the unloaded velocity of shortening (Vmax) of ASM was significantly increased upon 24 h co-incubation with antigen-stimulated CD4(+) T cells, while stress did not change. Enhanced Vmax was dependent upon contact between the CD4(+) T cells and the ASM and correlated with increased levels of the fast (+)insert smooth muscle myosin heavy chain isoform. The levels of myosin light chain kinase and myosin light chain phosphorylation were also increased within the muscle. The alterations in mechanics and in the levels of contractile proteins were transient, both declining to control levels after 48 h of co-incubation. More permanent alterations in muscle phenotype might be attainable when several inflammatory cells and mediators interact together or after repeated antigenic challenges. Further studies will await new tissue culture methodologies that preserve the muscle properties over longer periods of time. In conclusion, our data suggest that inflammatory cells promote ASM hypercontractility in airway hyper-responsiveness and asthma.

  10. The role of surfactant treatment in preterm infants and term newborns with acute respiratory distress syndrome. (United States)

    Wirbelauer, J; Speer, C P


    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.

  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


    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. Minimally Invasive Surfactant Therapy and Noninvasive Respiratory Support. (United States)

    Kribs, Angela


    Respiratory distress syndrome (RDS) caused by surfactant deficiency is major cause for neonatal mortality and short- and long-term morbidity of preterm infants. Continuous positive airway pressure and other modes of noninvasive respiratory support and intubation and positive pressure ventilation with surfactant therapy are efficient therapies for RDS. Because continuous positive airway pressure can fail in severe surfactant deficiency, and because traditional surfactant therapy requires intubation and positive pressure ventilation, this entails a risk of lung injury. Several strategies to combine noninvasive respiratory therapy with minimally invasive surfactant therapy have been described. Available data suggest that those strategies may improve outcome of premature infants with RDS.

  13. Rhinovirus infection induces extracellular matrix protein deposition in asthmatic and nonasthmatic airway smooth muscle cells

    NARCIS (Netherlands)

    Kuo, Curtis; Lim, Sam; King, Nicholas J C; Johnston, Sebastian L; Burgess, Janette K; Black, Judith L; Oliver, Brian G


    Airway remodeling, which includes increases in the extracellular matrix (ECM), is a characteristic feature of asthma and is correlated to disease severity. Rhinovirus (RV) infections are associated with increased risk of asthma development in young children and are the most common cause of asthma ex


    Institute of Scientific and Technical Information of China (English)

    P.M. Saville; J.W. White


    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.

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

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    Kell K Andersen


    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.

  16. Surfactant replacement therapy for preterm and term neonates with respiratory distress. (United States)

    Polin, Richard A; Carlo, Waldemar A


    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. 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.

  18. 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.

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

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    P.P.R. Lyra


    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.

  20. 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.

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

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    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

  2. A novel role of protein tyrosine kinase2 in mediating chloride secretion in human airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Lihua Liang

    Full Text Available Ca(2+ activated Cl(- channels (CaCC are up-regulated in cystic fibrosis (CF airway surface epithelia. The presence and functional properties of CaCC make it a possible therapeutic target to compensate for the deficiency of Cl(- secretion in CF epithelia. CaCC is activated by an increase in cytosolic Ca(2+, which not only activates epithelial CaCCs, but also inhibits epithelial Na(+ hyperabsorption, which may also be beneficial in CF. Our previous study has shown that spiperone, a known antipsychotic drug, activates CaCCs and stimulates Cl(- secretion in polarized human non-CF and CF airway epithelial cell monolayers in vitro, and in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR knockout mice in vivo. Spiperone activates CaCC not by acting in its well-known role as an antagonist of either 5-HT2 or D2 receptors, but through a protein tyrosine kinase-coupled phospholipase C-dependent pathway. Moreover, spiperone independently activates CFTR through a novel mechanism. Herein, we performed a mass spectrometry analysis and identified the signaling molecule that mediates the spiperone effect in activating chloride secretion through CaCC and CFTR. Proline-rich tyrosine kinase 2 (PYK2 is a non-receptor protein tyrosine kinase, which belongs to the focal adhesion kinase family. The inhibition of PYK2 notably reduced the ability of spiperone to increase intracellular Ca(2+ and Cl(- secretion. In conclusion, we have identified the tyrosine kinase, PYK2, as the modulator, which plays a crucial role in the activation of CaCC and CFTR by spiperone. The identification of this novel role of PYK2 reveals a new signaling pathway in human airway epithelial cells.

  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 (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


    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. Expression, stabilization and purification of membrane proteins via diverse protein synthesis systems and detergents involving cell-free associated with self-assembly peptide surfactants. (United States)

    Zheng, Xuan; Dong, Shuangshuang; Zheng, Jie; Li, Duanhua; Li, Feng; Luo, Zhongli


    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.

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


    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.

  6. Surfactant therapy in late preterm infants

    Directory of Open Access Journals (Sweden)

    Murat Yurdakök


    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

  7. 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;


    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...

  8. 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;


    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...

  9. Interactions of surfactants with a water treatment protein from Moringa oleifera seeds in solution studied by zeta-potential and light scattering measurements. (United States)

    Kwaambwa, Habauka M; Rennie, Adrian R


    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.

  10. Correlations of Ventricular Enlargement with Rheologically Active Surfactant Proteins in Cerebrospinal Fluid (United States)

    Schob, Stefan; Weiß, Alexander; Dieckow, Julia; Richter, Cindy; Pirlich, Mandy; Voigt, Peter; Surov, Alexey; Hoffmann, Karl-Titus; Quaeschling, Ulf; Preuß, Matthias


    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

  11. 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


    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 inserted and is therefore a candidate motif to participate in interactions with other bilayers or monolayers. In the present work, we have detected intrinsic ability of a peptide based on the sequence of the N-terminal segment of SP-C to interact and insert spontaneously into preformed zwitterionic....... These results demonstrate that the sequence of the SP-C N-terminal region has intrinsic ability to interact with, insert into, and perturb the structure of zwitterionic and anionic phospholipid films, even in the absence of the palmitic chains attached to this segment in the native protein. This effect has been...

  12. Trimethylangelicin promotes the functional rescue of mutant F508del CFTR protein in cystic fibrosis airway cells. (United States)

    Favia, Maria; Mancini, Maria T; Bezzerri, Valentino; Guerra, Lorenzo; Laselva, Onofrio; Abbattiscianni, Anna C; Debellis, Lucantonio; Reshkin, Stephan J; Gambari, Roberto; Cabrini, Giulio; Casavola, Valeria


    Cystic fibrosis transmembrane conductance regulator (CFTR) carrying the F508del mutation is retained in endoplasmic reticulum and fails to traffic to the cell surface where it functions as a protein kinase A (PKA)-activated chloride channel. Pharmacological correctors that rescue the trafficking of F508del CFTR may overcome this defect; however, the rescued F508del CFTR still displays reduced chloride permeability. Therefore, a combined administration of correctors and potentiators of the gating defect is ideal. We recently found that 4,6,4'-trimethylangelicin (TMA), besides inhibiting the expression of the IL-8 gene in airway cells in which the inflammatory response was challenged with Pseudomonas aeruginosa, also potentiates the cAMP/PKA-dependent activation of wild-type CFTR or F508del CFTR that has been restored to the plasma membrane. Here, we demonstrate that long preincubation with nanomolar concentrations of TMA is able to effectively rescue both F508del CFTR-dependent chloride secretion and F508del CFTR cell surface expression in both primary or secondary airway cell monolayers homozygous for F508del mutation. The correction effect of TMA seems to be selective for CFTR and persisted for 24 h after washout. Altogether, the results suggest that TMA, besides its anti-inflammatory and potentiator activities, also displays corrector properties.

  13. Alterations in nanoparticle protein corona by biological surfactants: impact of bile salts on β-lactoglobulin-coated gold nanoparticles. (United States)

    Winuprasith, Thunnalin; Chantarak, Sirinya; Suphantharika, Manop; He, Lili; McClements, David Julian


    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.

  14. Alcohol drives S-nitrosylation and redox activation of protein phosphatase 1, causing bovine airway cilia dysfunction. (United States)

    Price, Michael E; Pavlik, Jacqueline A; Liu, Miao; Ding, Shi-Jian; Wyatt, Todd A; Sisson, Joseph H


    Individuals with alcohol (ethanol)-use disorders are at increased risk for lung infections, in part, due to defective mucociliary clearance driven by motile cilia in the airways. We recently reported that isolated, demembranated bovine cilia (axonemes) are capable of producing nitric oxide ((∙)NO) when exposed to biologically relevant concentrations of alcohol. This increased presence of (∙)NO can lead to protein S-nitrosylation, a posttranslational modification signaling mechanism involving reversible adduction of nitrosonium cations or (∙)NO to thiolate or thiyl radicals, respectively, of proteins forming S-nitrosothiols (SNOs). We quantified and compared SNO content between isolated, demembranated axonemes extracted from bovine tracheae, with or without in situ alcohol exposure (100 mM × 24 h). We demonstrate that relevant concentrations of alcohol exposure shift the S-nitrosylation status of key cilia regulatory proteins, including 20-fold increases in S-nitrosylation of proteins that include protein phosphatase 1 (PP1). With the use of an ATP-reactivated axoneme motility system, we demonstrate that alcohol-driven S-nitrosylation of PP1 is associated with PP1 activation and dysfunction of axoneme motility. These new data demonstrate that alcohol can shift the S-nitrothiol balance at the level of the cilia organelle and highlight S-nitrosylation as a novel signaling mechanism to regulate PP1 and cilia motility.

  15. Prostaglandins but not leukotrienes alter extracellular matrix protein deposition and cytokine release in primary human airway smooth muscle cells and fibroblasts

    NARCIS (Netherlands)

    Van Ly, David; Burgess, Janette K.; Brock, Thomas G.; Lee, Tak H.; Black, Judith L.; Oliver, Brian G. G.


    Van Ly D, Burgess JK, Brock TG, Lee TH, Black JL, Oliver BG. Prostaglandins but not leukotrienes alter extracellular matrix protein deposition and cytokine release in primary human airway smooth muscle cells and fibroblasts. Am J Physiol Lung Cell Mol Physiol 303: L239-L250, 2012. First published Ma

  16. 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


    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...

  17. 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;


    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...

  18. Effects of the conjugation of whey proteins with gellan polysaccharides on surfactant-induced competitive displacement from the air-water interface. (United States)

    Cai, B; Ikeda, S


    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

  19. Mapping physiological G protein-coupled receptor signaling pathways reveals a role for receptor phosphorylation in airway contraction. (United States)

    Bradley, Sophie J; Wiegman, Coen H; Iglesias, Max Maza; Kong, Kok Choi; Butcher, Adrian J; Plouffe, Bianca; Goupil, Eugénie; Bourgognon, Julie-Myrtille; Macedo-Hatch, Timothy; LeGouill, Christian; Russell, Kirsty; Laporte, Stéphane A; König, Gabriele M; Kostenis, Evi; Bouvier, Michel; Chung, Kian Fan; Amrani, Yassine; Tobin, Andrew B


    G protein-coupled receptors (GPCRs) are known to initiate a plethora of signaling pathways in vitro. However, it is unclear which of these pathways are engaged to mediate physiological responses. Here, we examine the distinct roles of Gq/11-dependent signaling and receptor phosphorylation-dependent signaling in bronchial airway contraction and lung function regulated through the M3-muscarinic acetylcholine receptor (M3-mAChR). By using a genetically engineered mouse expressing a G protein-biased M3-mAChR mutant, we reveal the first evidence, to our knowledge, of a role for M3-mAChR phosphorylation in bronchial smooth muscle contraction in health and in a disease state with relevance to human asthma. Furthermore, this mouse model can be used to distinguish the physiological responses that are regulated by M3-mAChR phosphorylation (which include control of lung function) from those responses that are downstream of G protein signaling. In this way, we present an approach by which to predict the physiological/therapeutic outcome of M3-mAChR-biased ligands with important implications for drug discovery.

  20. Serum- and glucocorticoid-induced protein kinase 1 (SGK1) increases the cystic fibrosis transmembrane conductance regulator (CFTR) in airway epithelial cells by phosphorylating Shank2E protein. (United States)

    Koeppen, Katja; Coutermarsh, Bonita A; Madden, Dean R; Stanton, Bruce A


    The glucocorticoid dexamethasone increases cystic fibrosis transmembrane conductance regulator (CFTR) abundance in human airway epithelial cells by a mechanism that requires serum- and glucocorticoid-induced protein kinase 1 (SGK1) activity. The goal of this study was to determine whether SGK1 increases CFTR abundance by phosphorylating Shank2E, a PDZ domain protein that contains two SGK1 phosphorylation consensus sites. We found that SGK1 phosphorylates Shank2E as well as a peptide containing the first SGK1 consensus motif of Shank2E. The dexamethasone-induced increase in CFTR abundance was diminished by overexpression of a dominant-negative Shank2E in which the SGK1 phosphorylation sites had been mutated. siRNA-mediated reduction of Shank2E also reduced the dexamethasone-induced increase in CFTR abundance. Taken together, these data demonstrate that the glucocorticoid-induced increase in CFTR abundance requires phosphorylation of Shank2E at an SGK1 consensus site.

  1. 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


    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.

  2. 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;


    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...

  3. Proton-sensing ovarian cancer G protein-coupled receptor 1 on dendritic cells is required for airway responses in a murine asthma model. (United States)

    Aoki, Haruka; Mogi, Chihiro; Hisada, Takeshi; Nakakura, Takashi; Kamide, Yosuke; Ichimonji, Isao; Tomura, Hideaki; Tobo, Masayuki; Sato, Koichi; Tsurumaki, Hiroaki; Dobashi, Kunio; Mori, Tetsuya; Harada, Akihiro; Yamada, Masanobu; Mori, Masatomo; Ishizuka, Tamotsu; Okajima, Fumikazu


    Ovarian cancer G protein-coupled receptor 1 (OGR1) stimulation by extracellular protons causes the activation of G proteins and subsequent cellular functions. However, the physiological and pathophysiological roles of OGR1 in airway responses remain largely unknown. In the present study, we show that OGR1-deficient mice are resistant to the cardinal features of asthma, including airway eosinophilia, airway hyperresponsiveness (AHR), and goblet cell metaplasia, in association with a remarkable inhibition of Th2 cytokine and IgE production, in an ovalbumin (OVA)-induced asthma model. Intratracheal transfer to wild-type mice of OVA-primed bone marrow-derived dendritic cells (DCs) from OGR1-deficient mice developed lower AHR and eosinophilia after OVA inhalation compared with the transfer of those from wild-type mice. Migration of OVA-pulsed DCs to peribronchial lymph nodes was also inhibited by OGR1 deficiency in the adoption experiments. The presence of functional OGR1 in DCs was confirmed by the expression of OGR1 mRNA and the OGR1-sensitive Ca(2+) response. OVA-induced expression of CCR7, a mature DC chemokine receptor, and migration response to CCR7 ligands in an in vitro Transwell assay were attenuated by OGR1 deficiency. We conclude that OGR1 on DCs is critical for migration to draining lymph nodes, which, in turn, stimulates Th2 phenotype change and subsequent induction of airway inflammation and AHR.

  4. 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;


    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...

  5. 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;


    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....

  6. The Effect of Membrane Environment on Surfactant Protein C Stability Studied by Constant-pH Molecular Dynamics. (United States)

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


    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.

  7. Reduced expression of Tis7/IFRD1 protein in murine and human cystic fibrosis airway epithelial cell models homozygous for the F508del-CFTR mutation. (United States)

    Blanchard, Elise; Marie, Solenne; Riffault, Laure; Bonora, Monique; Tabary, Olivier; Clement, Annick; Jacquot, Jacky


    12-O-tetradecanoyl phorbol-13-acetate-induced sequence 7/interferon related development regulator 1 (Tis7/IFRD1) has been recently identified as a modifier gene in lung inflammatory disease severity in patients with cystic fibrosis (CF), based upon its capacity to regulate inflammatory activities in neutrophils. In CF patients, the F508del mutation in the Cftr gene encoding a chloride channel, the CF transmembrane conductance regulator (CFTR) in airway epithelial cells results in an exaggerated inflammatory response of these cells. At present, it is unknown whether the Tis7/IFRD1 gene product is expressed in airway epithelial cells. We therefore investigated the possibility there is an intrinsic alteration in Tis7/IFRD1 protein level in cells lacking CFTR function in tracheal homogenates of F508del-CFTR mice and in a F508del-CFTR human bronchial epithelial cell line (CFBE41o(-) cells). When Tis7/IFRD1 protein was detectable, trachea from F508del-CFTR mice showed a reduction in the level of Tis7/IFRD1 protein compared to wild-type control littermates. A significant reduction of IFRD1 protein level was found in CFBE41o(-) cells compared to normal bronchial epithelial cells 16HBE14o(-). Surprisingly, messenger RNA level of IFRD1 in CFBE41o(-) cells was found elevated. Treating CFBE41o(-) cells with the antioxidant glutathione rescued the IFRD1 protein level closer to control level and also reduced the pro-inflammatory cytokine IL-8 release. This work provides evidence for the first time of reduced level of IFRD1 protein in murine and human F508del-CFTR airway epithelial cell models, possibly mediated in response to oxidative stress which might contribute to the exaggerated inflammatory airway response observed in CF patients homozygous for the F508del mutation.

  8. Possible influence of surfactants and proteins on the efficiency of contact agar microbiological surface sampling. (United States)

    Deckers, Sylvie M; Sindic, Marianne; Anceau, Christine; Brostaux, Yves; Detry, Jean G


    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.

  9. 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


    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...... used to explore the effect of the presence of different phospholipids on the immunoreactivity of SP-B. Both polyclonal and monoclonal antibodies produced reproducible ELISA calibration curves for methanolic SP-B solutions with protein concentrations in the range of 20-1000 ng/mL. At these protein...... concentrations, neither dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylglycerol, nor phosphatidylcholine or phosphatidylglycerol from egg yolk had significant effects on the binding of antibodies to SP-B up to protein-to-lipid weight ratios of 1:20. Coating of ELISA plates with SP-B concentrations higher...

  10. Adsorption of proteins at the solution/air interface influenced by added nonionic surfactants at very low concentrations for both components. 3. Dilational surface rheology. (United States)

    Fainerman, V B; Aksenenko, E V; Lylyk, S V; Lotfi, M; Miller, R


    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.

  11. Impact of SDS surfactant on the interactions of Cu(2+) ions with the amyloidogenic region of human prion protein. (United States)

    Hecel, Aleksandra; Migliorini, Caterina; Valensin, Daniela; Luczkowski, Marek; Kozlowski, Henryk


    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.

  12. Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Young-Il [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Kim, Seung Hyun [Div. of AIDS, National Institute of Health, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Ju, Jung Won; Cho, Shin Hyeong; Lee, Won Ja [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Park, Jin Wook; Park, Yeong-Min [Dept. of Microbiology and Immunology, College of Medicine, Pusan National University, Yang-San (Korea, Republic of); Lee, Sang Eun, E-mail: [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of)


    Highlights: {yields} Treatment with Clonorchis sinensis-derived total protein attenuates OVA-induced airway inflammation and AHR to methacholine. {yields} Induction of CD4{sup +}CD25{sup +}Foxp3{sup +} T cells and IL-10 along with suppression of splenocyte proliferation by C. sinensis-derived total protein. {yields} C. sinensis-derived total protein interferes with the expression of co-stimulatory molecules in DCs. -- Abstract: Asthma is characterized by Th2-mediated inflammation, resulting in airway hyperresponsiveness (AHR) through airway remodeling. Recent epidemiological and experimental reports have suggested an inverse relationship between the development of allergy and helminth infections. Infection by Clonorchis sinensis, a liver fluke that resides in the bile duct of humans, is endemic predominantly in Asia including Korea and China. Using a murine model for asthma, we investigated the effects of C. sinensis-derived total protein (Cs-TP) on allergen-induced airway inflammation and the mechanism underlying the protective effects of Cs-TP administration on asthma. Treatment with Cs-TP attenuated OVA-induced airway inflammation and methacholine-induced AHR, as well as eosinophilia development, lymphocyte infiltration into the lung, and goblet cell metaplasia. This protective effect of Cs-TP is associated with markedly reduced OVA-specific IgE and Th1/Th2 cytokine production. Moreover, Cs-TP increased the number of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T (Treg) cells as well as their suppressive activity. In fact, proliferation of OVA-restimulated splenocytes was suppressed significantly. Cs-TP also inhibited the expression of such co-stimulatory molecules as CD80, CD86, and CD40 in LPS- or OVA-stimulated dendritic cells (DCs), suggesting that Cs-TP could interfere with the capacity of airway DCs to prime naive T cells. These data demonstrate the capacity of C. sinensis to ameliorate allergic asthma and broaden our understanding of the paradoxical

  13. Virulence Factors of Pseudomonas aeruginosa Induce Both the Unfolded Protein and Integrated Stress Responses in Airway Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Emily F A van 't Wout


    Full Text Available Pseudomonas aeruginosa infection can be disastrous in chronic lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease. Its toxic effects are largely mediated by secreted virulence factors including pyocyanin, elastase and alkaline protease (AprA. Efficient functioning of the endoplasmic reticulum (ER is crucial for cell survival and appropriate immune responses, while an excess of unfolded proteins within the ER leads to "ER stress" and activation of the "unfolded protein response" (UPR. Bacterial infection and Toll-like receptor activation trigger the UPR most likely due to the increased demand for protein folding of inflammatory mediators. In this study, we show that cell-free conditioned medium of the PAO1 strain of P. aeruginosa, containing secreted virulence factors, induces ER stress in primary bronchial epithelial cells as evidenced by splicing of XBP1 mRNA and induction of CHOP, GRP78 and GADD34 expression. Most aspects of the ER stress response were dependent on TAK1 and p38 MAPK, except for the induction of GADD34 mRNA. Using various mutant strains and purified virulence factors, we identified pyocyanin and AprA as inducers of ER stress. However, the induction of GADD34 was mediated by an ER stress-independent integrated stress response (ISR which was at least partly dependent on the iron-sensing eIF2α kinase HRI. Our data strongly suggest that this increased GADD34 expression served to protect against Pseudomonas-induced, iron-sensitive cell cytotoxicity. In summary, virulence factors from P. aeruginosa induce ER stress in airway epithelial cells and also trigger the ISR to improve cell survival of the host.

  14. 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


    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.

  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;


    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


    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. Sodium cromoglycate on plasma protein exudation to topically-applied substance P in the tracheal airways of rats or guinea-pigs in vivo. (United States)

    O'Donnell, S R; Coulson, F R; Bigg, C S


    Sodium cromoglycate (SCG) was examined against substance P(SP)-induced plasma protein exudation in the trachea of anaesthetized rats and guinea-pigs in vivo to determine whether SCG is a tachykinin receptor antagonist in the airways. A segment of trachea was prepared in situ for continuous perfusion with normal saline. Plasma-derived protein in the perfusion fluid (airway lumen) was increased after topical application of SP (1 microM, 5 min contact). In rats, the SP response was not attenuated by iv SCG but was inhibited (29%) by topical SCG under certain experimental conditions and using a high concentration of SCG (500 microM, 5 min contact, 30 min before SP and with SP). The NK(1)receptor antagonist, RP 67 580 (67 microM) abolished the SP response in rats. Sodium cromoglycate did not inhibit the SP response in guinea-pigs (same protocol as in rats). Thus, SCG attenuates plasma protein exudation (and presumably microvascular leak) induced by SP in rat tracheal airways but, if SCG is a tachykinin receptor (NK(1)) antagonist, it not only lacks potency but is species-selective, i.e. more effective in rats than in guinea-pigs.

  18. Surfactant gene polymorphisms and interstitial lung diseases

    Directory of Open Access Journals (Sweden)

    Pantelidis Panagiotis


    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.

  19. Ultrastructural study of nuclear inclusions immunohistochemically positive for surfactant protein A in pulmonary adenocarcinoma with special reference to their morphogenesis. (United States)

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


    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.

  20. Monomeric G-proteins as signal transducers in airway physiology and pathophysiology

    NARCIS (Netherlands)

    Schaafsma, Dedmer; Roscioni, Sara S.; Meurs, Herman; Schmidt, Martina


    Monomeric G-proteins, also referred to as small GTPases, function as biological hubs being activated by extracellular stimuli and regulate downstream signalling events, which result in different cellular responses. The importance of these mechanisms is mirrored by the fact that several pathological

  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


    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 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.;


    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...

  3. Evaluation of C-reactive protein, Haptoglobin and cardiac troponin 1 levels in brachycephalic dogs with upper airway obstructive syndrome

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    Planellas Marta


    Full Text Available Abstract Background Brachycephalic dogs have unique upper respiratory anatomy with abnormal breathing patterns similar to those in humans with obstructive sleep apnea syndrome (OSAS. The objective of this study was to evaluate the correlation between anatomical components, clinical signs and several biomarkers, used to determine systemic inflammation and myocardial damage (C-reactive protein, CRP; Haptoglobin, Hp; cardiac troponin I, cTnI, in dogs with brachycephalic upper airway obstructive syndrome (BAOS. Results Fifty brachycephalic dogs were included in the study and the following information was studied: signalment, clinical signs, thoracic radiographs, blood work, ECG, components of BAOS, and CRP, Hp and cTnI levels. A high proportion of dogs with BAOS (88% had gastrointestinal signs. The prevalence of anatomic components of BAOS was: elongated soft palate (100%, stenotic nares (96%, everted laryngeal saccules (32% and tracheal hypoplasia (29.1%. Increased serum levels of biomarkers were found in a variable proportion of dogs: 14% (7/50 had values of CRP > 20 mg/L, 22.9% (11/48 had values of Hp > 3 g/L and 47.8% (22/46 had levels of cTnI > 0.05 ng/dl. Dogs with everted laryngeal saccules had more severe respiratory signs (p Conclusions According to the low percentage of patients with elevated levels of CRP and Hp, BAOS does not seem to cause an evident systemic inflammatory status. Some degree of myocardial damage may occur in dogs with BAOS that can be detected by cTnI concentration.

  4. 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


    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.

  5. Pulmonary surfactant protein A inhibits the lipid peroxidation stimulated by linoleic acid hydroperoxide of rat lung mitochondria and microsomes. (United States)

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


    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

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

    DEFF Research Database (Denmark)

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


    with identical N-terminal tags remote from the ligand-binding surface. Although rat and mouse showed similar affinities for saccharide competitors, both differed markedly from the human protein. The human neck+CRD preferentially recognized N-acetyl-mannosamine, whereas the rat and mouse proteins showed greater...... of the corresponding murine sequence (Asn324-Asn325) conferred a capacity to interact with immobilized maltose. Thus, ligand recognition by human SP-D involves a complex interplay between saccharide presentation, the valency of trimeric subunits, and species-specific residues that flank the primary carbohydrate...

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

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    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.

  8. Activation of protein kinase C accelerates contraction kinetics of airway smooth muscle. (United States)

    Peiper, U; Knipp, S C; Thies, B; Henke, R


    Contraction kinetics of isolated rat tracheal smooth muscle were studied by analysing the increase of force subsequent to force-inhibiting passive length changes lasting 1 s (100 Hz, sinus, 5% of muscle length). Compared with carbachol activation, phorboldibutyrate (PDBu)-induced stimulation of protein kinase C (PKC) demonstrated no significant difference in the extent of force development in the polarized preparation [mean peak force 9.16 +/- 0.37 mN (carbachol) vs. 9.12 +/- 0.37 mN (PDBu)]. However, the time constant calculated for the slow component of post-vibration force recovery was 6.40 +/- 0.29 s after addition of PDBu vs. 22.39 +/- 1.40 s during carbachol activation, indicating a significant phorbol ester-induced acceleration of the cross-bridge cycling rate. In the K-depolarized preparation, treatment with 26.4 microM indolactam (IL) to activate PKC produced muscle relaxation (9.94 +/- 0.16 mN measured 0-30 min after the onset of depolarization vs. 4.13 +/- 0.05 mN measured during 30-60 min of IL treatment). Again, even in the presence of high sarcoplasmic Ca2+ resulting from tonic depolarization, PKC activation was associated with a distinct diminution of the time constant (25.99 +/- 0.79 s during the first 30 min of depolarization vs. 10.32 +/- 0.21 s during 30-60 min of IL treatment). In contrast, addition of 0.035 microM verapamil, 1.5 microM isoproterenol, and 32 microM dibutyryl-cAMP to the bathing medium induced relaxation without affecting the rate of post-vibration force recovery. The results suggest that the calcium-dependent signal cascade (agonist receptor/inositol trisphosphate/ Ca(2+)-calmodulin/myosin light chain kinase) hardly affects the regulation of contraction kinetics in the tonically activated intact smooth muscle preparation. PKC stimulation, however, accelerates actin/myosin interaction kinetics, possibly by inhibition of phosphatase(s).

  9. 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


    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。

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

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    Kajiki Akira


    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

  11. The human airway epithelial basal cell transcriptome.

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    Neil R Hackett

    Full Text Available BACKGROUND: The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population. METHODOLOGY/PRINCIPAL FINDINGS: Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the "human airway basal cell signature" as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels. CONCLUSION/SIGNIFICANCE: The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of

  12. 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


    -C-derived peptides or recombinant humanized SP-C for inclusion in new preparations for therapeutic use. We describe herein the recombinant production in bacterial cultures of SP-C variants containing phenylalanines instead of the palmitoylated cysteines of the native protein, as fusions to the hydrophilic nuclease...... A (SN) from Staphylococcus aureus. The resulting chimerae were partially purified by affinity chromatography and subsequently subjected to protease digestion. The SP-C forms were recovered from the digestion mixtures by organic extraction and further purified by size exclusion chromatography. The two...

  13. Study of the binding between lysozyme and C10-TAB: determination and interpretation of the partial properties of protein and surfactant at infinite dilution. (United States)

    Morgado, Jorge; Aquino-Olivos, Marco Antonio; Martínez-Hernández, Ranulfo; Corea, Mónica; Grolier, Jean Pierre E; del Río, José Manuel


    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.

  14. The application of eosinophil cationic protein on inflammatory disease of airway%ECP在气道变应性疾病中的应用进展

    Institute of Scientific and Technical Information of China (English)



    Eosinophil cationic protein(ECP)is a heterogeneous molecule originating from activated eosinophil granulocytes.Airway allergic diseases such as allergic rhinitis and asthma are closely related eosinophils that Infiltrate local tissue.ECP can be actively used in the diagnosis of allergic disease,curative effect evaluations as a biomarker.The origin and the biology function of ECP as well as its relations with the infection are introduced,espcially,the relationship between ECP and ashma、allergic rhinitis are also addressed.

  15. A Common Polymorphism in the SFTPD Gene Influences Assembly, Function, and Concentration of Surfactant Protein D

    DEFF Research Database (Denmark)

    Leth-Larsen, Rikke; Garred, Peter; Jensenius, Henriette;


    on epithelial surfaces and in serum. Genotyping for three single-nucleotide variations altering amino acids in the mature protein in codon 11 (Met(11)Thr), 160 (Ala(160)Thr), and 270 (Ser(270)Thr) of the SP-D gene was performed and related to the SP-D levels in serum. Individuals with the Thr/Thr(11)-encoding...... the second peak exclusively contains monomers. SP-D from both peaks bound to mannan-coated ELISA plates. SP-D from the high m.w. peak bound preferentially to intact influenza A virus and Gram-positive and Gram-negative bacteria, whereas the monomeric species preferentially bound to isolated LPS. Our data...... strongly suggest that polymorphic variation in the N-terminal domain of the SP-D molecule influences oligomerization, function, and the concentration of the molecule in serum....

  16. A common polymorphism in the SFTPD gene influences assembly, function, and concentration of surfactant protein D

    DEFF Research Database (Denmark)

    Leth-Larsen, Rikke; Garred, Peter; Jensenius, Henriette;


    on epithelial surfaces and in serum. Genotyping for three single-nucleotide variations altering amino acids in the mature protein in codon 11 (Met(11)Thr), 160 (Ala(160)Thr), and 270 (Ser(270)Thr) of the SP-D gene was performed and related to the SP-D levels in serum. Individuals with the Thr/Thr(11)-encoding...... the second peak exclusively contains monomers. SP-D from both peaks bound to mannan-coated ELISA plates. SP-D from the high m.w. peak bound preferentially to intact influenza A virus and Gram-positive and Gram-negative bacteria, whereas the monomeric species preferentially bound to isolated LPS. Our data...... strongly suggest that polymorphic variation in the N-terminal domain of the SP-D molecule influences oligomerization, function, and the concentration of the molecule in serum....

  17. 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.

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


    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.

  19. 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.

  20. Non-ionic Surfactants and Non-Catalytic Protein Treatment on Enzymatic Hydrolysis of Pretreated Creeping Wild Ryegrass (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.

  1. Polymorphisms in the surfactant protein a gene are associated with the susceptibility to recurrent urinary tract infection in chinese women. (United States)

    Liu, Jiao; Hu, Fengqi; Liang, Wei; Wang, Guirong; Singhal, Pravin C; Ding, Guohua


    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.

  2. 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


    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.

  3. Comparison of surfactant protein B polymorphisms of healthy term newborns with preterm newborns having respiratory distress syndrome. (United States)

    Lyra, P P R; Vaz, F A C; Moreira, P E; Hoffmann, J W; Demello, D E; Diniz, E M A


    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.

  4. Anti-inflammatory effects of Tat-Annexin protein on ovalbumin-induced airway inflammation in a mouse model of asthma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sun Hwa; Kim, Dae Won; Kim, Hye Ri; Woo, Su Jung; Kim, So Mi; Jo, Hyo Sang [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Jeon, Seong Gyu [Department of Life Science, Pohang University of Science and Technology, Pohang 790-784 (Korea, Republic of); Cho, Sung-Woo [Department of Biochemistry and Molecular Biology, University of Ulsan, College of Medicine, Seoul 138-736 (Korea, Republic of); Park, Jong Hoon [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Won, Moo Ho [Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Park, Jinseu [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Eum, Won Sik, E-mail: [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Choi, Soo Young, E-mail: [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of)


    Highlights: Black-Right-Pointing-Pointer We construct a cell permeable Tat-ANX1 fusion protein. Black-Right-Pointing-Pointer We examined the protective effects of Tat-ANX1 protein on OVA-induced asthma in animal models. Black-Right-Pointing-Pointer Transduced Tat-ANX1 protein protects from the OVA-induced production of cytokines and eosinophils in BAL fluid. Black-Right-Pointing-Pointer Tat-ANX1 protein markedly reduced OVA-induced MAPK in lung tissues. Black-Right-Pointing-Pointer Tat-ANX1 protein could be useful as a therapeutic agent for lung disorders including asthma. -- Abstract: Chronic airway inflammation is a key feature of bronchial asthma. Annexin-1 (ANX1) is an anti-inflammatory protein that is an important modulator and plays a key role in inflammation. Although the precise action of ANX1 remains unclear, it has emerged as a potential drug target for inflammatory diseases such as asthma. To examine the protective effects of ANX1 protein on ovalbumin (OVA)-induced asthma in animal models, we used a cell-permeable Tat-ANX1 protein. Mice sensitized and challenged with OVA antigen had an increased amount of cytokines and eosinophils in their bronchoalveolar lavage (BAL) fluid. However, administration of Tat-ANX1 protein before OVA challenge significantly decreased the levels of cytokines (interleukin (IL)-4, IL-5, and IL-13) and BAL fluid in lung tissues. Furthermore, OVA significantly increased the activation of mitogen-activated protein kinase (MAPK) in lung tissues, whereas Tat-ANX1 protein markedly reduced phosphorylation of MAPKs such as extracellular signal-regulated protein kinase, p38, and stress-activated protein kinase/c-Jun N-terminal kinase. These results suggest that transduced Tat-ANX1 protein may be a potential protein therapeutic agent for the treatment of lung disorders including asthma.

  5. A Recombinant DNA Plasmid Encoding the sIL-4R-NAP Fusion Protein Suppress Airway Inflammation in an OVA-Induced Mouse Model of Asthma. (United States)

    Liu, Xin; Fu, Guo; Ji, Zhenyu; Huang, Xiabing; Ding, Cong; Jiang, Hui; Wang, Xiaolong; Du, Mingxuan; Wang, Ting; Kang, Qiaozhen


    Asthma is a chronic inflammatory airway disease. It was prevalently perceived that Th2 cells played the crucial role in asthma pathogenesis, which has been identified as the important target for anti-asthma therapy. The soluble IL-4 receptor (sIL-4R), which is the decoy receptor for Th2 cytokine IL-4, has been reported to be effective in treating asthma in phase I/II clinical trail. To develop more efficacious anti-asthma agent, we attempt to test whether the Helicobacter pylori neutrophil-activating protein (HP-NAP), a novel TLR2 agonist, would enhance the efficacy of sIL-4R in anti-asthma therapy. In our work, we constructed a pcDNA3.1-sIL-4R-NAP plasmid, named PSN, encoding fusion protein of murine sIL-4R and HP-NAP. PSN significantly inhibited airway inflammation, decreased the serum OVA-specific IgE levels and remodeled the Th1/Th2 balance. Notably, PSN is more effective on anti-asthma therapy comparing with plasmid only expressing sIL-4R.

  6. Innovation in surfactant therapy I: surfactant lavage and surfactant administration by fluid bolus using minimally invasive techniques. (United States)

    Dargaville, Peter A


    Innovation in the field of exogenous surfactant therapy continues more than two decades after the drug became commercially available. One such innovation, lung lavage using dilute surfactant, has been investigated in both laboratory and clinical settings as a treatment for meconium aspiration syndrome (MAS). Studies in animal models of MAS have affirmed that dilute surfactant lavage can remove meconium from the lung, with resultant improvement in lung function. In human infants both non-randomised studies and two randomised controlled trials have demonstrated a potential benefit of dilute surfactant lavage over standard care. The largest clinical trial, performed by our research group in infants with severe MAS, found that lung lavage using two 15-ml/kg aliquots of dilute surfactant did not reduce the duration of respiratory support, but did appear to reduce the composite outcome of death or need for extracorporeal membrane oxygenation. A further trial of lavage therapy is planned to more precisely define the effect on survival. Innovative approaches to surfactant therapy have also extended to the preterm infant, for whom the more widespread use of continuous positive airway pressure (CPAP) has meant delaying or avoiding administration of surfactant. In an effort to circumvent this problem, less invasive techniques of bolus surfactant therapy have been trialled, including instillation directly into the pharynx, via laryngeal mask and via brief tracheal catheterisation. In a recent clinical trial, instillation of surfactant into the trachea using a flexible feeding tube was found to reduce the need for subsequent intubation. We have developed an alternative method of brief tracheal catheterisation in which surfactant is delivered via a semi-rigid vascular catheter inserted through the vocal cords under direct vision. In studies to date, this technique has been relatively easy to perform, and resulted in rapid improvement in lung function and reduced need for

  7. 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.


    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....

  8. Inhibition of protein kinase C delta attenuates allergic airway inflammation through suppression of PI3K/Akt/mTOR/HIF-1 alpha/VEGF pathway.

    Directory of Open Access Journals (Sweden)

    Yun Ho Choi

    Full Text Available Vascular endothelial growth factor (VEGF is supposed to contribute to the pathogenesis of allergic airway disease. VEGF expression is regulated by a variety of stimuli such as nitric oxide, growth factors, and hypoxia-inducible factor-1 alpha (HIF-1α. Recently, inhibition of the mammalian target of rapamycin (mTOR has been shown to alleviate cardinal asthmatic features, including airway hyperresponsiveness, eosinophilic inflammation, and increased vascular permeability in asthma models. Based on these observations, we have investigated whether mTOR is associated with HIF-1α-mediated VEGF expression in allergic asthma. In studies with the mTOR inhibitor rapamycin, we have elucidated the stimulatory role of a mTOR-HIF-1α-VEGF axis in allergic response. Next, the mechanisms by which mTOR is activated to modulate this response have been evaluated. mTOR is known to be regulated by phosphoinositide 3-kinase (PI3K/Akt or protein kinase C-delta (PKC δ in various cell types. Consistent with these, our results have revealed that suppression of PKC δ by rottlerin leads to the inhibition of PI3K/Akt activity and the subsequent blockade of a mTOR-HIF-1α-VEGF module, thereby attenuating typical asthmatic attack in a murine model. Thus, the present data indicate that PKC δ is necessary for the modulation of the PI3K/Akt/mTOR signaling cascade, resulting in a tight regulation of HIF-1α activity and VEGF expression. In conclusion, PKC δ may represent a valuable target for innovative therapeutic treatment of allergic airway disease.

  9. Surfactant Protein A and B Gene Polymorphisms and Risk of Respiratory Distress Syndrome in Late-Preterm Neonates (United States)

    Tsitoura, Maria-Eleni I.; Stavrou, Eleana F.; Maraziotis, Ioannis A.; Sarafidis, Kosmas; Athanassiadou, Aglaia; Dimitriou, Gabriel


    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

  10. Dual function of novel pollen coat (surface proteins: IgE-binding capacity and proteolytic activity disrupting the airway epithelial barrier.

    Directory of Open Access Journals (Sweden)

    Mohamed Elfatih H Bashir

    Full Text Available BACKGROUND: The pollen coat is the first structure of the pollen to encounter the mucosal immune system upon inhalation. Prior characterizations of pollen allergens have focused on water-soluble, cytoplasmic proteins, but have overlooked much of the extracellular pollen coat. Due to washing with organic solvents when prepared, these pollen coat proteins are typically absent from commercial standardized allergenic extracts (i.e., "de-fatted", and, as a result, their involvement in allergy has not been explored. METHODOLOGY/PRINCIPAL FINDINGS: Using a unique approach to search for pollen allergenic proteins residing in the pollen coat, we employed transmission electron microscopy (TEM to assess the impact of organic solvents on the structural integrity of the pollen coat. TEM results indicated that de-fatting of Cynodon dactylon (Bermuda grass pollen (BGP by use of organic solvents altered the structural integrity of the pollen coat. The novel IgE-binding proteins of the BGP coat include a cysteine protease (CP and endoxylanase (EXY. The full-length cDNA that encodes the novel IgE-reactive CP was cloned from floral RNA. The EXY and CP were purified to homogeneity and tested for IgE reactivity. The CP from the BGP coat increased the permeability of human airway epithelial cells, caused a clear concentration-dependent detachment of cells, and damaged their barrier integrity. CONCLUSIONS/SIGNIFICANCE: Using an immunoproteomics approach, novel allergenic proteins of the BGP coat were identified. These proteins represent a class of novel dual-function proteins residing on the coat of the pollen grain that have IgE-binding capacity and proteolytic activity, which disrupts the integrity of the airway epithelial barrier. The identification of pollen coat allergens might explain the IgE-negative response to available skin-prick-testing proteins in patients who have positive symptoms. Further study of the role of these pollen coat proteins in allergic

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

    Enhorning, G


    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.

  12. CRP-ductin, the mouse homologue of gp-340/deleted in malignant brain tumors 1 (DMBT1), binds gram-positive and gram-negative bacteria and interacts with lung surfactant protein D

    DEFF Research Database (Denmark)

    Madsen, Jens; Tornøe, Ida; Nielsen, Ole;


    CRP-ductin is a protein expressed mainly by mucosal epithelial cells in the mouse. Sequence homologies indicate that CRP-ductin is the mouse homologue of human gp-340, a glycoprotein that agglutinates microorganisms and binds the lung mucosal collectin surfactant protein-D (SP-D). Here we report...

  13. Differential Gene Expression Profiles and Selected Cytokine Protein Analysis of Mediastinal Lymph Nodes of Horses with Chronic Recurrent Airway Obstruction (RAO Support an Interleukin-17 Immune Response.

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    Alexandra Korn

    Full Text Available Recurrent airway obstruction (RAO is a pulmonary inflammatory condition that afflicts certain mature horses exposed to organic dust particulates in hay. Its clinical and pathological features, manifested by reversible bronchoconstriction, excessive mucus production and airway neutrophilia, resemble the pulmonary alterations that occur in agricultural workers with occupational asthma. The immunological basis of RAO remains uncertain although its chronicity, its localization to a mucosal surface and its domination by a neutrophilic, non-septic inflammatory response, suggest involvement of Interleukin-17 (IL-17. We examined global gene expression profiles in mediastinal (pulmonary-draining lymph nodes isolated from RAO-affected and control horses. Differential expression of > 200 genes, coupled with network analysis, supports an IL-17 response centered about NF-κB. Immunohistochemical analysis of mediastinal lymph node sections demonstrated increased IL-17 staining intensity in diseased horses. This result, along with the finding of increased IL-17 concentrations in lymph node homogenates from RAO-affected horses (P = 0.1 and a down-regulation of IL-4 gene and protein expression, provides additional evidence of the involvement of IL-17 in the chronic stages of RAO. Additional investigations are needed to ascertain the cellular source of IL-17 in this equine model of occupational asthma. Understanding the immunopathogenesis of this disorder likely will enhance the development of therapeutic interventions beneficial to human and animal pulmonary health.

  14. 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

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    Mason Robert J


    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

  15. Constitutively active signaling by the G protein βγ-subunit mediates intrinsically increased phosphodiesterase-4 activity in human asthmatic airway smooth muscle cells.

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    Aihua Hu

    Full Text Available Signaling by the Gβγ subunit of Gi protein, leading to downstream c-Src-induced activation of the Ras/c-Raf1/MEK-ERK1/2 signaling pathway and its upregulation of phosphodiesterase-4 (PDE4 activity, was recently shown to mediate the heightened contractility in proasthmatic sensitized isolated airway smooth muscle (ASM, as well as allergen-induced airway hyperresponsiveness and inflammation in an in vivo animal model of allergic asthma. This study investigated whether cultured human ASM (HASM cells derived from asthmatic donor lungs exhibit constitutively increased PDE activity that is attributed to intrinsically upregulated Gβγ signaling coupled to c-Src activation of the Ras/MEK/ERK1/2 cascade. We show that, relative to normal cells, asthmatic HASM cells constitutively exhibit markedly increased intrinsic PDE4 activity coupled to heightened Gβγ-regulated phosphorylation of c-Src and ERK1/2, and direct co-localization of the latter with the PDE4D isoform. These signaling events and their induction of heightened PDE activity are acutely suppressed by treating asthmatic HASM cells with a Gβγ inhibitor. Importantly, along with increased Gβγ activation, asthmatic HASM cells also exhibit constitutively increased direct binding of the small Rap1 GTPase-activating protein, Rap1GAP, to the α-subunit of Gi protein, which serves to cooperatively facilitate Ras activation and, thereby, enable enhanced Gβγ-regulated ERK1/2-stimulated PDE activity. Collectively, these data are the first to identify that intrinsically increased signaling via the Gβγ subunit, facilitated by Rap1GAP recruitment to the α-subunit, mediates the constitutively increased PDE4 activity detected in asthmatic HASM cells. These new findings support the notion that interventions targeted at suppressing Gβγ signaling may lead to novel approaches to treat asthma.

  16. 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)


    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.

  17. Postdeposition dispersion of aerosol medications using surfactant carriers. (United States)

    Marcinkowski, Amy L; Garoff, Stephen; Tilton, Robert D; Pilewski, Joseph M; Corcoran, Timothy E


    Inhaled aerosol drugs provide a means of directly treating the lungs; however, aerosol deposition and drug distribution can be nonuniform, especially in obstructive lung disease. We hypothesize that surfactant-based aerosol carriers will disperse medications over airway surfaces after deposition through surface tension driven flows, increasing dose uniformity and improving drug distribution into underventilated regions. We considered saline and surfactant aerosol delivery via cannula onto several model airway surfaces including porcine gastric mucus (PGM) and both cystic fibrosis (CF) and non-CF human bronchial epithelial cells (HBEs). Fluorescent dye and microspheres (d = 100 nm, 1 mum) were used to qualitatively and quantitatively assess postdeposition dispersion. Aerosol volume median diameters were in the 1-4 mum range. The tested surfactants included sodium dodecyl sulfate (SDS), cetyl trimethyl ammonium bromide (CTAB), tyloxapol, and calfactant. All surfactants tested on PGM (tyloxapol, calfactant, SDS, and CTAB) significantly increased dispersion area versus saline with all markers (2-20-fold increases; all p surfactants tested on CF HBEs (tyloxapol and calfactant) significantly increased dispersion area versus saline with all markers (1.6-4.1-fold increases; all p Surfactant carriers enhanced dispersion after aerosol deposition onto model airway surfaces, and may improve the efficacy of inhaled preparations such as inhaled antibiotics for cystic fibrosis.

  18. Airway management in trauma

    Directory of Open Access Journals (Sweden)

    Rashid M Khan


    Full Text Available Trauma has assumed epidemic proportion. 10% of global road accident deaths occur in India. Hypoxia and airway mismanagement are known to contribute up to 34% of pre-hospital deaths in these patients. A high degree of suspicion for actual or impending airway obstruction should be assumed in all trauma patients. Objective signs of airway compromise include agitation, obtundation, cyanosis, abnormal breath sound and deviated trachea. If time permits, one should carry out a brief airway assessment prior to undertaking definitive airway management in these patients. Simple techniques for establishing and maintaining airway patency include jaw thrust maneuver and/or use of oro- and nas-opharyngeal airways. All attempts must be made to perform definitive airway management whenever airway is compromised that is not amenable to simple strategies. The selection of airway device and route- oral or -nasal, for tracheal intubation should be based on nature of patient injury, experience and skill level.

  19. Surfactant protein D levels in umbilical cord blood and capillary blood of premature infants. The influence of perinatal factors

    DEFF Research Database (Denmark)

    Dahl, Marianne; Holmskov, Uffe; Husby, Steffen


    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...

  20. Pharmacogenetics, pharmacogenomics and airway disease

    Directory of Open Access Journals (Sweden)

    Hall Ian P


    Full Text Available Abstract The availability of a draft sequence for the human genome will revolutionise research into airway disease. This review deals with two of the most important areas impinging on the treatment of patients: pharmacogenetics and pharmacogenomics. Considerable inter-individual variation exists at the DNA level in targets for medication, and variability in response to treatment may, in part, be determined by this genetic variation. Increased knowledge about the human genome might also permit the identification of novel therapeutic targets by expression profiling at the RNA (genomics or protein (proteomics level. This review describes recent advances in pharmacogenetics and pharmacogenomics with regard to airway disease.

  1. Absorption-enhancing effects of gemini surfactant on the intestinal absorption of poorly absorbed hydrophilic drugs including peptide and protein drugs in rats. (United States)

    Alama, Tammam; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira


    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.

  2. 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


    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.

  3. Airway distensibility in Chronic Obstructive Airway Disease

    DEFF Research Database (Denmark)

    Winkler Wille, Mathilde Marie; Pedersen, Jesper Holst; Dirksen, Asger


    -20% (mild), 20%-30% (moderate) or >30% (severe). Spirometry was performed annually and participants were divided into severity groups according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Data were analysed in a mixed effects regression model with log(airway lumen diameter......Rationale – Chronic Obstructive Pulmonary Disease (COPD) is a combination of chronic bronchitis and emphysema, which both may lead to airway obstruction. Under normal circumstances, airway dimensions vary as a function of inspiration level. We aim to study the influence of COPD and emphysema...... in causing airway narrowing, the latter most likely due to loss of elastic recoil of surrounding tissue....

  4. Dissociation of FK506-binding protein 12.6 kD from ryanodine receptor in bronchial smooth muscle cells in airway hyperresponsiveness in asthma. (United States)

    Du, Ying; Zhao, Jianhong; Li, Xi; Jin, Si; Ma, Wan-Li; Mu, Qing; Xu, Shuxiang; Yang, Jie; Rao, Shanshan; Zhu, Liping; Xin, Jianbao; Cai, Peng-Cheng; Su, Yunchao; Ye, Hong


    Airway hyperresponsiveness (AHR) in asthma is predominantly caused by increased sensitivity of bronchial smooth muscle cells (BSMCs) to stimuli. The sarcoplasmic reticulum (SR)-Ca(2+) release channel, known as ryanodine receptor (RyR), mediates the contractive response of BSMCs to stimuli. FK506-binding protein 12.6 kD (FKBP12.6) stabilizes the RyR2 channel in a closed state. However, the interaction of FKBP12.6 with RyR2 in AHR remains unknown. This study examined the interaction of FKBP12.6 with RyR2 in BSMCs in AHR of asthma. The interaction of FKBP12.6 with RyR2 and FKBP12.6 expression was determined in a rat asthma model and in BSMCs treated with inflammatory cytokines. The calcium responses to contractile agonists were determined in BSMCs with overexpression and knockdown of FKBP12.6. Asthmatic serum, IL-5, IL-13, and TNF-α enhance the calcium response of BSMCs to contractile agonists and cause dissociation of FKBP12.6 from RyR2 and a decrease in FKBP12.6 gene expression in BSMCs in culture and in ovalbumin (OVA)-sensitized and -challenged rats. Knockdown of FKBP12.6 in BSMCs causes a decrease in the association of RyR2 with FKBP12.6 and an increase in the calcium response of BSMCs. Overexpression of FKBP12.6 increases the association of FKBP12.6 with RyR2, decreases the calcium response of BSMCs, and normalizes airway responsiveness in OVA-sensitized and -challenged rats. Dissociation of FKBP12.6 from RyR2 in BSMCs is responsible for the increased calcium response contributing to AHR in asthma. Manipulating the interaction of FKBP12.6 with RyR2 might be a novel and useful treatment for asthma.

  5. 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: [Department of Chemistry, Birla Institute of Technology and Science, Pilani 333031, Rajasthan (India)


    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

  6. 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.

  7. 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;


    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...... diurnal variation in healthy controls (n = 15) and in patients with ERA (n = 9) and LRA (n = 9) with peak values at 10 a.m. and nadir in the evening (controls: P exercise levels in both...... ERA (n = 10), LRA (n = 10) and controls (n = 13) (ERA: P exercise. Circulating SP-D exhibits diurnal variation both in patients with RA at different stages and in healthy controls. SP...

  8. 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:


    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.

  9. Macrophages and dendritic cells express tight junction proteins and exchange particles in an in vitro model of the human airway wall. (United States)

    Blank, Fabian; Wehrli, Marc; Lehmann, Andrea; Baum, Oliver; Gehr, Peter; von Garnier, Christophe; Rothen-Rutishauser, Barbara M


    The human airway epithelium serves as structural and functional barrier against inhaled particulate antigen. Previously, we demonstrated in an in vitro epithelial barrier model that monocyte derived dendritic cells (MDDC) and monocyte derived macrophages (MDM) take up particulate antigen by building a trans-epithelial interacting network. Although the epithelial tight junction (TJ) belt was penetrated by processes of MDDC and MDM, the integrity of the epithelium was not affected. These results brought up two main questions: (1) Do MDM and MDDC exchange particles? (2) Are those cells expressing TJ proteins, which are believed to interact with the TJ belt of the epithelium to preserve the epithelial integrity? The expression of TJ and adherens junction (AJ) mRNA and proteins in MDM and MDDC monocultures was determined by RT-PCR, and immunofluorescence, respectively. Particle uptake and exchange was quantified by flow cytometry and laser scanning microscopy in co-cultures of MDM and MDDC exposed to polystyrene particles (1 μm in diameter). MDM and MDDC constantly expressed TJ and AJ mRNA and proteins. Flow cytometry analysis of MDM and MDDC co-cultures showed increased particle uptake in MDDC while MDM lost particles over time. Quantitative analysis revealed significantly higher particle uptake by MDDC in co-cultures of epithelial cells with MDM and MDDC present, compared to co-cultures containing only epithelial cells and MDDC. We conclude from these findings that MDM and MDDC express TJ and AJ proteins which could help to preserve the epithelial integrity during particle uptake and exchange across the lung epithelium.

  10. Structural effects of pH and deacylation on surfactant protein C in an organic solvent mixture: a constant-pH MD study. (United States)

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


    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.

  11. Relative Contribution of P5 and Hap Surface Proteins to Nontypable Haemophilus influenzae Interplay with the Host Upper and Lower Airways. (United States)

    Euba, Begoña; Moleres, Javier; Viadas, Cristina; Ruiz de los Mozos, Igor; Valle, Jaione; Bengoechea, José Antonio; Garmendia, Junkal


    Nontypable Haemophilus influenzae (NTHi) is a major cause of opportunistic respiratory tract disease, and initiates infection by colonizing the nasopharynx. Bacterial surface proteins play determining roles in the NTHi-airways interplay, but their specific and relative contribution to colonization and infection of the respiratory tract has not been addressed comprehensively. In this study, we focused on the ompP5 and hap genes, present in all H. influenzae genome sequenced isolates, and encoding the P5 and Hap surface proteins, respectively. We employed isogenic single and double mutants of the ompP5 and hap genes generated in the pathogenic strain NTHi375 to evaluate P5 and Hap contribution to biofilm growth under continuous flow, to NTHi adhesion, and invasion/phagocytosis on nasal, pharyngeal, bronchial, alveolar cultured epithelial cells and alveolar macrophages, and to NTHi murine pulmonary infection. We show that P5 is not required for bacterial biofilm growth, but it is involved in NTHi interplay with respiratory cells and in mouse lung infection. Mechanistically, P5NTHi375 is not a ligand for CEACAM1 or α5 integrin receptors. Hap involvement in NTHi375-host interaction was shown to be limited, despite promoting bacterial cell adhesion when expressed in H. influenzae RdKW20. We also show that Hap does not contribute to bacterial biofilm growth, and that its absence partially restores the deficiency in lung infection observed for the ΔompP5 mutant. Altogether, this work frames the relative importance of the P5 and Hap surface proteins in NTHi virulence.

  12. Thermally cleavable surfactants (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.


    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 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.

  13. 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)


    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 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.

  14. 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)


    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 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.

  15. Effects of transforming growth factor-[beta] and budesonide on mitogen-activated protein kinase activation and apoptosis in airway epithelial cells. (United States)

    Pelaia, Girolamo; Cuda, Giovanni; Vatrella, Alessandro; Fratto, Donatella; Grembiale, Rosa D; Tagliaferri, Pierosandro; Maselli, Rosario; Costanzo, Francesco S; Marsico, Serafino A


    Airway epithelial cells play a central role in the inflammatory, apoptotic, and remodeling processes associated with asthma. Within this context, a key function is exerted by transforming growth factor-beta (TGF-beta), whose biological effects are mediated at least in part by mitogen-activated protein kinases (MAPKs). The aim of our study was to investigate, in primary cultures of human bronchial epithelial cells (HBEC), the effects of TGF-beta (10 ng/ml) on both MAPK activation and apoptosis, in the presence or absence of a pretreatment with budesonide (10-8 M). MAPK activation was detected by Western blotting, using anti-phospho-MAPK monoclonal antibodies, which specifically recognize the phosphorylated, active forms of these enzymes. Apoptosis was assayed by caspase-3 activation and fluorescence microscopy, using annexin-V (An-V) and propidium iodide (PI) as markers of cell death. Our results show that TGF-beta induced a marked ( reverse similar 9-fold) increase in p38 MAPK phosphorylation, and also dramatically enhanced cell death, which was completely prevented by specific MAPK inhibitors. Both MAPK activation and apoptosis were effectively inhibited by budesonide (BUD), thereby suggesting that the powerful antiapoptotic action of inhaled glucocorticoids may be very important for their protective role against epithelial injury, which represents a key pathogenic event in asthma.

  16. Focal adhesion kinase regulates collagen I-induced airway smooth muscle phenotype switching

    NARCIS (Netherlands)

    Dekkers, Bart G J; Spanjer, Anita I R; van der Schuyt, Robert D; Kuik, Willem Jan; Zaagsma, Johan; Meurs, Herman


    Increased extracellular matrix (ECM) deposition and airway smooth muscle (ASM) mass are major contributors to airway remodeling in asthma. Recently, we demonstrated that the ECM protein collagen I, which is increased surrounding asthmatic ASM, induces a proliferative, hypocontractile ASM phenotype.

  17. Distending Pressure Did Not Activate Acute Phase or Inflammatory Responses in the Airways and Lungs of Fetal, Preterm Lambs.

    Directory of Open Access Journals (Sweden)

    Rebecca Y Petersen

    Full Text Available Mechanical ventilation at birth causes airway injury and lung inflammation in preterm sheep. Continuous positive airway pressure (CPAP is being increasingly used clinically to transition preterm infants at birth.To test if distending pressures will activate acute phase reactants and inflammatory changes in the airways of fetal, preterm lambs.The head and chest of fetal lambs at 128±1 day GA were surgically exteriorized. With placental circulation intact, fetal lambs were then randomized to one of five 15 minute interventions: PEEP of 0, 4, 8, 12, or 16 cmH2O. Recruitment volumes were recorded. Fetal lambs remained on placental support for 30 min after the intervention. The twins of each 0 cmH2O animal served as controls. Fetal lung fluid (FLF, bronchoalveolar lavage fluid (BAL, right mainstem bronchi and peripheral lung tissue were evaluated for inflammation.Recruitment volume increased from 0.4±0.04 mL/kg at 4 cmH2O to 2.4±0.3 mL/kg at 16 cmH2O. The lambs were surfactant deficient, and all pressures were below the opening inflection pressure on pressure-volume curve. mRNA expression of early response genes and pro-inflammatory cytokines did not increase in airway tissue or lung tissue at any pressure compared to controls. FLF and BAL also did not have increases in early response proteins. No histologic changes or Egr-1 activation was present at the pressures used.Distending pressures as high as 16 cmH2O did not recruit lung volume at birth and did not increase markers of injury in the lung or airways in non-breathing preterm fetal sheep.

  18. Engineering Airway Epithelium

    Directory of Open Access Journals (Sweden)

    John P. Soleas


    Full Text Available Airway epithelium is constantly presented with injurious signals, yet under healthy circumstances, the epithelium maintains its innate immune barrier and mucociliary elevator function. This suggests that airway epithelium has regenerative potential (I. R. Telford and C. F. Bridgman, 1990. In practice, however, airway regeneration is problematic because of slow turnover and dedifferentiation of epithelium thereby hindering regeneration and increasing time necessary for full maturation and function. Based on the anatomy and biology of the airway epithelium, a variety of tissue engineering tools available could be utilized to overcome the barriers currently seen in airway epithelial generation. This paper describes the structure, function, and repair mechanisms in native epithelium and highlights specific and manipulatable tissue engineering signals that could be of great use in the creation of artificial airway epithelium.

  19. Central airways remodeling in COPD patients

    Directory of Open Access Journals (Sweden)

    Pini L


    Full Text Available Laura Pini,1 Valentina Pinelli,2 Denise Modina,1 Michela Bezzi,3 Laura Tiberio,4 Claudio Tantucci1 1Unit of Respiratory Medicine, Department of Clinical and Experimental Sciences, University of Brescia, 2Department of Respiratory Medicine, Spedali Civili di Brescia, 3Department Bronchoscopy, Spedali Civili di Brescia, 4Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy Background: The contribution to airflow obstruction by the remodeling of the peripheral airways in chronic obstructive pulmonary disease (COPD patients has been well documented, but less is known about the role played by the large airways. Few studies have investigated the presence of histopathological changes due to remodeling in the large airways of COPD patients. Objectives: The aim of this study was to verify the presence of airway remodeling in the central airways of COPD patients, quantifying the airway smooth muscle (ASM area and the extracellular matrix (ECM protein deposition, both in the subepithelial region and in the ASM, and to verify the possible contribution to airflow obstruction by the above mentioned histopathological changes. Methods: Biopsies of segmental bronchi spurs were performed in COPD patients and control smoker subjects and immunostained for collagen type I, versican, decorin, biglycan, and alpha-smooth muscle actin. ECM protein deposition was measured at both subepithelial, and ASM layers. Results: The staining for collagen I and versican was greater in the subepithelial layer of COPD patients than in control subjects. An inverse correlation was found between collagen I in the subepithelial layer and both forced expiratory volume in 1 second and ratio between forced expiratory volume in 1 second and forced vital capacity. A statistically significant increase of the ASM area was observed in the central airways of COPD patients versus controls. Conclusion: These findings indicate that airway remodeling also affects

  20. Predictors of Airway Hyperresponsiveness in Elite Athletes

    DEFF Research Database (Denmark)

    Toennesen, Louise L; Porsbjerg, Celeste; Pedersen, Lars;


    INTRODUCTION: Elite athletes frequently suffer from asthma and airway hyperresponsiveness (AHR). We aimed to investigate predictors of airway pathophysiology in a group of unselected elite summer-sport athletes, training for the summer 2008 Olympic Games, including markers of airway inflammation......, systemic inflammation and training intensity. METHODS: 57 Danish elite summer-sport athletes with and without asthma symptoms all gave a blood sample for measurements of high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF....... In these subjects, no association was found between the levels of AHR to mannitol and methacholine (r=0.032, p=0.91). CONCLUSION: Airway hyperresponsiveness in elite athletes is related to the amount of weekly training and the level of serum TNF-α. No association was found between the level of AHR to mannitol...

  1. Airway management in trauma

    Directory of Open Access Journals (Sweden)

    Rao B


    Full Text Available Airway Management for the victims of major trauma is the first priority in the care of the trauma victim and is a core skill in emergency medicine and critical care. Endotracheal intubation remains the gold standard for trauma airway management. Airway management in trauma patients is not just the capability to insert an oral/nasal airway or endotracheal tube beyond the vocal cords. The five components integral to modern, sophisticated airway management in trauma patients include equipment, pharmacologic adjuncts, manual techniques, physical circumstances, and patient profile. A trauma patient may require airway management in a variety of physical circumstances. Whereas, the commonly used airway management algorithms may not suffice in all these situations, the construction of a truly complete decision tree is also virtually impossible. There is consensus that it is not the intervention per se but rather the conditions, skills, and performance that might be the possible variables that affect outcome. Paramedics have only limited experience and on-the-job skills for invasive airway management. Difficult airway management is best left for the experienced physicians to handle.

  2. Controlling Nonspecific Protein Adsorption in a Plug-Based Microfluidic System by Controlling Interfacial Chemistry Using Fluorous-Phase Surfactants


    Roach, L. Spencer; Song, Helen; Ismagilov, Rustem F.


    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...

  3. 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


    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.

  4. 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. (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


    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.

  5. Indirect airway challenges

    NARCIS (Netherlands)

    Joos, GF; O'Connor, B; Anderson, SD; Chung, F; Cockcroft, DW; Dahlen, B; DiMaria, G; Foresi, A; Hargreave, FE; Holgate, ST; Inman, M; Lotvall, J; Magnussen, H; Polosa, R; Postma, DS; Riedler, J


    Indirect challenges act by causing the release of endogenous mediators that cause the airway smooth muscle to contract. This is in contrast to the direct challenges where agonists such as methacholine or histamine cause airflow limitation predominantly via a direct effect on airway smooth muscle. Di

  6. Pediatric airway nightmares. (United States)

    D'Agostino, James


    Pediatric disorders that involve actual or potential airway compromise are among the most challenging cases that emergency department providers face. This article discusses the diagnosis and management of common and uncommon conditions in infants and children who may present with airway obstruction.

  7. Role of IRE1α/XBP-1 in Cystic Fibrosis Airway Inflammation

    Directory of Open Access Journals (Sweden)

    Carla M. P. Ribeiro


    Full Text Available Cystic fibrosis (CF pulmonary disease is characterized by chronic airway infection and inflammation. The infectious and inflamed CF airway environment impacts on the innate defense of airway epithelia and airway macrophages. The CF airway milieu induces an adaptation in these cells characterized by increased basal inflammation and a robust inflammatory response to inflammatory mediators. Recent studies have indicated that these responses depend on activation of the unfolded protein response (UPR. This review discusses the contribution of airway epithelia and airway macrophages to CF airway inflammatory responses and specifically highlights the functional importance of the UPR pathway mediated by IRE1/XBP-1 in these processes. These findings suggest that targeting the IRE1/XBP-1 UPR pathway may be a therapeutic strategy for CF airway disease.

  8. 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. (United States)

    Samten, Buka; Townsend, James C; Sever-Chroneos, Zvjezdana; Pasquinelli, Virginia; Barnes, Peter F; Chroneos, Zissis C


    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.

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


    (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

  10. Airway smooth muscle and fibroblasts in the pathogenesis of asthma

    NARCIS (Netherlands)

    Johnson, Peter R A; Burgess, Janette K


    Asthma is a disease characterized by marked structural changes within the airway wall. These changes include deposition of extracellular matrix proteins and an increase in the numbers of airway smooth muscle cells and subepithelial fibroblasts. Both these cell types possess properties that would ena

  11. Post-translational processing of surfactant protein-C proprotein: targeting motifs in the NH(2)-terminal flanking domain are cleaved in late compartments. (United States)

    Johnson, A L; Braidotti, P; Pietra, G G; Russo, S J; Kabore, A; Wang, W J; Beers, M F


    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

  12. 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


    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

  13. Chronic respiratory aeroallergen exposure in mice induces epithelial-mesenchymal transition in the large airways.

    Directory of Open Access Journals (Sweden)

    Jill R Johnson

    Full Text Available Chronic allergic asthma is characterized by Th2-polarized inflammation and leads to airway remodeling and fibrosis but the mechanisms involved are not clear. To determine whether epithelial-mesenchymal transition contributes to airway remodeling in asthma, we induced allergic airway inflammation in mice by intranasal administration of house dust mite (HDM extract for up to 15 consecutive weeks. We report that respiratory exposure to HDM led to significant airway inflammation and thickening of the smooth muscle layer in the wall of the large airways. Transforming growth factor beta-1 (TGF-β1 levels increased in mouse airways while epithelial cells lost expression of E-cadherin and occludin and gained expression of the mesenchymal proteins vimentin, alpha-smooth muscle actin (α-SMA and pro-collagen I. We also observed increased expression and nuclear translocation of Snail1, a transcriptional repressor of E-cadherin and a potent inducer of EMT, in the airway epithelial cells of HDM-exposed mice. Furthermore, fate-mapping studies revealed migration of airway epithelial cells into the sub-epithelial regions of the airway wall. These results show the contribution of EMT to airway remodeling in chronic asthma-like inflammation and suggest that Th2-polarized airway inflammation can trigger invasion of epithelial cells into the subepithelial regions of the airway wall where they contribute to fibrosis, demonstrating a previously unknown plasticity of the airway epithelium in allergic airway disease.

  14. Surfactants in tribology

    CERN Document Server

    Biresaw, Girma


    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

  15. 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;


    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...

  16. 14-3-3 isoforms bind directly exon B of the 5'-UTR of human surfactant protein A2 mRNA. (United States)

    Noutsios, Georgios T; Ghattas, Paul; Bennett, Stephanie; Floros, Joanna


    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.

  17. Dendrimer-surfactant interactions. (United States)

    Cheng, Yiyun; Zhao, Libo; Li, Tianfu


    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.

  18. 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. (United States)

    Kurimura, Yuichiro; Nishitani, Chiaki; Ariki, Shigeru; Saito, Atsushi; Hasegawa, Yoshihiro; Takahashi, Motoko; Hashimoto, Jiro; Takahashi, Satoshi; Tsukamoto, Taiji; Kuroki, Yoshio


    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.

  19. Can Serum Surfactant Protein D or CC-Chemokine Ligand 18 Predict Outcome of Interstitial Lung Disease in Patients with Early Systemic Sclerosis? (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


    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

  20. Surfactant Sector Needs Urgent Readjustment

    Institute of Scientific and Technical Information of China (English)

    Huang Hongzhou


    @@ 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.

  1. 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


    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.

  2. Effect of Cigarette Smoke Extract on the Role of Protein Kinase C in the Proliferation of Passively Sensitized Human Airway Smooth Muscle Cells

    Institute of Scientific and Technical Information of China (English)

    LIN Junling; XU Yongjian; ZHANG Zhenxiang; NI Wang; CHEN Shixin


    Summary: To investigate the effect of cigarette smoke extract (CSE) on the role of protein kinase C (PKC) in the proliferation of passively sensitized human airway smooth muscle cells (HASMCs). After synchronization of cultured HASMCs, they were divided into a group A and Group B. The group A was treated with normal human serum and served as controls and the group B was treated with the serum of asthma patients. The group A was further divided into group of A1, A2 and A3 and the group B was sub-divided into the group of B1, B2, B3, B4 and B5. No other agents were added to the group A1 and B1. The cells of group A2 and B2 were stimulated with 5 % CSE for 24 h. HASMCs from group A3 and B3 were treated with PKC agonist PMA (10 nmol/L) and CSE (5 %) for 24 h. PKC inhibitor Ro-31-8220 (5 μmol/L) was added to the HASMCs of group B4 for 24 h. The cells from group B5 were stimulated with Ro-31-8220 (5 μmol/L) and CSE (5 %) for 24 h. The proliferation of HASMCs isolated from group A and B was examined by cell cycle analysis, MTT colorimetric assay and 3H-TdR incorporation test. The expression of PKC-α in each group was observed by Western blotting and RT-PCR, respectively. The results showed that the percentage of S phase, absorbance (A) value, the rate of 3H-TdR incorporation, the ratios of A value of PKC-α mRNA and the A value of PKC-α protein in HASMCs from group B1, B2 and B3 were significantly increased compared to those of group A1, A2 and A3 correspondingly and respectively (P<0.01). The proliferation of HASMCs of group A2 and B2 stimulated with CSE and group A3 and B3 stimulated with CSE and PMA were also significantly enhanced when group A1, A2 and A3 and group B1, B2 and B3 compared to each other (P<0.05, P<0.01, respectively). The percentage of S phase, absorbency (A) value, 3H-TdR incorporation rate, the ratios of A value of PKC-α mRNA and the A value of PKC-α protein in HASMCs from group B4 treated with Ro-31-8220 and group B5 treated with CSE and Ro-31

  3. Emergency airway puncture - slideshow (United States)

    ... presentations/100113.htm Emergency airway puncture - series—Normal anatomy To ... larynx is a tubular structure in the neck, through which air passes to the lungs. The thryoid and cricoid cartilage form the narrowest ...

  4. Emergency airway puncture (United States)

    ... inserted into the throat, just below the Adam's apple (cricoid cartilage), into the airway. In a hospital, ... Choking Browse the Encyclopedia A.D.A.M., Inc. is accredited by URAC, also known as the ...

  5. TNFα and IFNγ synergistically enhance transcriptional activation of CXCL10 in human airway smooth muscle cells via STAT-1, NF-κB, and the transcriptional coactivator CREB-binding protein. (United States)

    Clarke, Deborah L; Clifford, Rachel L; Jindarat, Sarawut; Proud, David; Pang, Linhua; Belvisi, Maria; Knox, Alan J


    Asthmatic airway smooth muscle (ASM) expresses interferon-γ-inducible protein-10 (CXCL10), a chemokine known to mediate mast cell migration into ASM bundles that has been reported in the airways of asthmatic patients. CXCL10 is elevated in patients suffering from viral exacerbations of asthma and in patients with chronic obstructive pulmonary disease (COPD), diseases in which corticosteroids are largely ineffective. IFNγ and TNFα synergistically induce CXCL10 release from human ASM cells in a steroid-insensitive manner, via an as yet undefined mechanism. We report that TNFα activates the classical NF-κB (nuclear factor κB) pathway, whereas IFNγ activates JAK2/STAT-1α and that inhibition of the JAK/STAT pathway is more effective in abrogating CXCL10 release than the steroid fluticasone. The synergy observed with TNFα and IFNγ together, however, did not lie at the level of NF-κB activation, STAT-1α phosphorylation, or in vivo binding of these transcription factors to the CXCL10 promoter. Stimulation of human ASM cells with TNFα and IFNγ induced histone H4 but not histone H3 acetylation at the CXCL10 promoter, although no synergism was observed when both cytokines were combined. We show, however, that TNFα and IFNγ exert a synergistic effect on the recruitment of CREB-binding protein (CBP) to the CXCL10, which is accompanied by increased RNA polymerase II. Our results provide evidence that synergism between TNFα and IFNγ lies at the level of coactivator recruitment in human ASM and suggest that inhibition of JAK/STAT signaling may be of therapeutic benefit in steroid-resistant airway disease.

  6. Airway management in trauma. (United States)

    Langeron, O; Birenbaum, A; Amour, J


    Maintenance of a patent and prevention of aspiration are essential for the management of the trauma patient, that requires experienced physicians in airway control techniques. Difficulties of the airway control in the trauma setting are increased by the vital failures, the risk of aspiration, the potential cervical spine injury, the combative patient, and the obvious risk of difficult tracheal intubation related to specific injury related to the trauma. Endotracheal intubation remains the gold standard in trauma patient airway management and should be performed via the oral route with a rapid sequence induction and a manual in-line stabilization maneuver, to decrease the risks previously mentioned. Different techniques to control the airway in trauma patients are presented: improvement of the laryngoscopic vision, lighted stylet tracheal intubation, retrograde technique for orotracheal intubation, the laryngeal mask and the intubating laryngeal mask airways, the combitube and cricothyroidotomy. Management of the airway in trauma patients requires regular training in these techniques and the knowledge of complementary techniques allowing tracheal intubation or oxygenation to overcome difficult intubation and to prevent major complications as hypoxemia and aspiration.

  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


    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...


    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...

  9. 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;


    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...

  10. [Pulmonary surfactant homeostasis associated genetic abnormalities and lung diseases]. (United States)

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


    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.

  11. Comparative study on nasal continuous positive airway pressure combined with pulmonary surfactant in treatment of premature infants' Hyaline membrane disease%鼻塞式持续气道正压通气联合肺表面活性物质治疗早产儿肺透明膜病对照研究

    Institute of Scientific and Technical Information of China (English)

    刘勇; 程国平


    Objective To study the difference in curative effects of nasal continuous positive airway pressure (NCPAP) combined with pulmonary surfactant (PS) and NCPAP combined with Mucosolvan ( MU) on premature infants' Hyaline membrane disease ( HMD). Methods 90 premature infants with HMD were randomly divided into NCPAP combined with PS ( NC + PS treatment) group and MU ( NC + MU treatment) group. Curative effects, arterial blood gas, short and long term complications were compared after treatment. Results ( NC + PS) group' s total effective rate was higher than ( NC + MU) group, while the time of dyspnea remission , respirator treatment and mean hospitalization were lower than ( NC + MU) group with statistical significance (P 0.05 ) . They all increased after treatment except PaCO2, the differences in both group had statistical significance ( P < 0. 05 ). The main short term complications were pneumonia, intracranial hemorrhage and pulmonary hemorrhage; the main long term complications were cerebral palsy, hearing disorder and retinopathy of prematurity. Comprehensive situation in short and long term complications were significantly better in (NC + PS) group than (NC +MU) group (P<0.05). Conclusion NCPAP combined with PS could significantly promote curative effect on hyaline membrane disease with few short and long term complications. It is significantly better than NCPAP combined withMU.%目的 探讨鼻塞式持续气道正压通气(NCPAP)联合肺表面活性物质(PS)和NCPAP联合沐舒坦(MU)两种方法治疗早产儿肺透明膜病的疗效差异.方法 将90例肺透明膜病(HMD)早产儿随机分为NCPAP联合PS(NC+PS治疗组)和NCPAP联合MU(NC+ MU治疗组),分别进行治疗,并比较两组的疗效、动脉血气分析和近远期并发症的差异.结果 (NC+PS)组的总有效率显著高于( NC+ MU)组,而在呼吸困难缓解时间、上呼吸机时间和平均住院时间方面均小于(NC+MU)组,两组间的差异具有统计学意义(P<0.05).治

  12. Clinical comparison of early prophylactic application of nasal continuous positive airway pressure and pulmonary surfactant in the premature very low birth weight infants%早产极低出生体重儿早期预防性应用鼻塞式持续气道正压与肺表面活性物质的临床比较

    Institute of Scientific and Technical Information of China (English)

    高薇薇; 谭三智; 杨杰; 张永; 叶秀桢; 聂川; 王越; 王俊平


    目的:探讨在早产极低出生体重儿中生后早期使用鼻塞式持续气道正压(nCPAP)或应用肺表面活性剂(PS)以预防新生儿呼吸窘迫综合征(NRDS)的临床疗效比较.方法:采用前瞻性对照研究,对出生后早期使用nCPAP辅助通气或早期使用PS替代治疗的早产极低出生体重儿进行对照研究,观察其死亡率、支气管肺发育不良发生率、辅助通气时间及临床并发症.结果:共106例患儿人选,死亡率和支气管肺发育不良(BPD)发生率组间比较差异无统计学意义.机械辅助通气、总用氧时间组间比较差异无统计学意义;nCPAP组PS使用数少于对照组(Odds Ratio:0.37,90% CI 0.209~0.655);气漏发生率低(Odds Ratio:0.476,90% CI0.233~0.971),IVH发生率低(Odds Ratio:o.778,90%CI 0.319~1.898).其他临床并发症组间比较差异无统计学意义.结论:早期应用nCPAP是预防早产极低出生体重儿呼吸窘迫综合征另一良好选择.%Objective; To explore the clinical effects of early prophylactic application of nasal continuous positive airway pressure (nCPAP) and pulmonary surfactant (PS) in prevention of neonatal respiratory distress syndrome ( NROS) among the premature very low birth weight infants. Methods: The clinical effects of early prophylactic application of nCPAP and PS in the premature very low birth weight infants were compared, the death rates, the incidences of bronchopulmonary dysplasia, the duration times of assisted ventilation, and clinical complications in the two groups were observed. Results; A total of 106 infants were enrolled in the study. There was no significant difference in the death rate and the incidence of bronchopulmonary dysplasia between the two groups. There was no significant difference in the duration time of mechanical ventilation and total using oxygen time between the two groups; the number of infants using PS in nCPAP group was fewer than that in control group (Odds ratio; 0. 37, 90

  13. Salivary agglutinin and lung scavenger receptor cysteine-rich glycoprotein 340 have broad anti-influenza activities and interactions with surfactant protein D that vary according to donor source and sialylation

    DEFF Research Database (Denmark)

    Hartshorn, Kevan L.; Ligtenberg, Antoon; White, Mitchell R.;


    from this donor as compared with salivary gp-340 from another donor or several preparations of lung gp-340. Hence, the specificity of sialic acid linkages on gp-340 is an important determinant of anti-IAV activity. Gp-340 binds to SP-D (surfactant protein D), and we previously showed that lung gp-340...... has co-operative interactions with SP-D in viral neutralization and aggregation assays. We now report that salivary gp-340 can, in some cases, strongly antagonize certain antiviral activities of SP-D. This effect was associated with greater binding of salivary gp-340 to the carbohydrate recognition...

  14. Surfactants in the environment. (United States)

    Ivanković, Tomislav; Hrenović, Jasna


    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.

  15. Metathesis depolymerizable surfactants (United States)

    Jamison, Gregory M.; Wheeler, David R.; Loy, Douglas A.; Simmons, Blake A.; Long, Timothy M.; McElhanon, James R.; Rahimian, Kamyar; Staiger, Chad L.


    A class of surfactant molecules whose structure includes regularly spaced unsaturation in the tail group and thus, can be readily decomposed by ring-closing metathesis, and particularly by the action of a transition metal catalyst, to form small molecule products. These small molecules are designed to have increased volatility and/or enhanced solubility as compared to the original surfactant molecule and are thus easily removed by solvent extraction or vacuum extraction at low temperature. By producing easily removable decomposition products, the surfactant molecules become particularly desirable as template structures for preparing meso- and microstructural materials with tailored properties.

  16. Integrated care pathways for airway diseases (AIRWAYS-ICPs)

    NARCIS (Netherlands)

    Bousquet, J.; Addis, A.; Adcock, I.; Agache, I.; Agusti, A.; Alonso, A.; Annesi-Maesano, I.; Anto, J. M.; Bachert, C.; Baena-Cagnani, C. E.; Bai, C.; Baigenzhin, A.; Barbara, C.; Barnes, P. J.; Bateman, E. D.; Beck, L.; Bedbrook, A.; Bel, E. H.; Benezet, O.; Bennoor, K. S.; Benson, M.; Bernabeu-Wittel, M.; Bewick, M.; Bindslev-Jensen, C.; Blain, H.; Blasi, F.; Bonini, M.; Bonini, S.; Boulet, L. P.; Bourdin, A.; Bourret, R.; Bousquet, P. J.; Brightling, C. E.; Briggs, A.; Brozek, J.; Buh, R.; Bush, A.; Caimmi, D.; Calderon, M.; Calverley, P.; Camargos, P. A.; Camuzat, T.; Canonica, G. W.; Carlsen, K. H.; Casale, T. B.; Cazzola, M.; Sarabia, A. M. Cepeda; Cesario, A.; Chen, Y. Z.; Chkhartishvili, E.; Chavannes, N. H.; Chiron, R.; Chuchalin, A.; Chung, K. F.; Cox, L.; Crooks, G.; Crooks, M. G.; Cruz, A. A.; Custovic, A.; Dahl, R.; Dahlen, S. E.; De Blay, F.; Dedeu, T.; Deleanu, D.; Demoly, P.; Devillier, P.; Didier, A.; Dinh-Xuan, A. T.; Djukanovic, R.; Dokic, D.; Douagui, H.; Dubakiene, R.; Eglin, S.; Elliot, F.; Emuzyte, R.; Fabbri, L.; Wagner, A. Fink; Fletcher, M.; Fokkens, W. J.; Fonseca, J.; Franco, A.; Frith, P.; Furber, A.; Gaga, M.; Garces, J.; Garcia-Aymerich, J.; Gamkrelidze, A.; Gonzales-Diaz, S.; Gouzi, F.; Guzman, M. A.; Haahtela, T.; Harrison, D.; Hayot, M.; Heaney, L. G.; Heinrich, J.; Hellings, P. W.; Hooper, J.; Humbert, M.; Hyland, M.; Iaccarino, G.; Jakovenko, D.; Jardim, J. R.; Jeandel, C.; Jenkins, C.; Johnston, S. L.; Jonquet, O.; Joos, G.; Jung, K. S.; Kalayci, O.; Karunanithi, S.; Keil, T.; Khaltaev, N.; Kolek, V.; Kowalski, M. L.; Kull, I.; Kuna, P.; Kvedariene, V.; Le, L. T.; Carlsen, K. C. Lodrup; Louis, R.; MacNee, W.; Mair, A.; Majer, I.; Manning, P.; Keenoy, E. de Manuel; Masjedi, M. R.; Meten, E.; Melo-Gomes, E.; Menzies-Gow, A.; Mercier, G.; Mercier, J.; Michel, J. P.; Miculinic, N.; Mihaltan, F.; Milenkovic, B.; Molimard, M.; Mamas, I.; Montilla-Santana, A.; Morais-Almeida, M.; Morgan, M.; N'Diaye, M.; Nafti, S.; Nekam, K.; Neou, A.; Nicod, L.; O'Hehir, R.; Ohta, K.; Paggiaro, P.; Palkonen, S.; Palmer, S.; Papadopoulos, N. G.; Papi, A.; Passalacqua, G.; Pavord, I.; Pigearias, B.; Plavec, D.; Postma, D. S.; Price, D.; Rabe, K. F.; Pontal, F. Radier; Redon, J.; Rennard, S.; Roberts, J.; Robine, J. M.; Roca, J.; Roche, N.; Rodenas, F.; Roggeri, A.; Rolland, C.; Rosado-Pinto, J.; Ryan, D.; Samolinski, B.; Sanchez-Borges, M.; Schunemann, H. J.; Sheikh, A.; Shields, M.; Siafakas, N.; Sibille, Y.; Similowski, T.; Small, I.; Sola-Morales, O.; Sooronbaev, T.; Stelmach, R.; Sterk, P. J.; Stiris, T.; Sud, P.; Tellier, V.; To, T.; Todo-Bom, A.; Triggiani, M.; Valenta, R.; Valero, A. L.; Valiulis, A.; Valovirta, E.; Van Ganse, E.; Vandenplas, O.; Vasankari, T.; Vestbo, J.; Vezzani, G.; Viegi, G.; Visier, L.; Vogelmeier, C.; Vontetsianos, T.; Wagstaff, R.; Wahn, U.; Wallaert, B.; Whalley, B.; Wickman, M.; Williams, D. M.; Wilson, N.; Yawn, B. P.; Yiallouros, P. K.; Yorgancioglu, A.; Yusuf, O. M.; Zar, H. J.; Zhong, N.; Zidarn, M.; Zuberbier, T.


    The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will ad

  17. Airway reconstruction in children

    Directory of Open Access Journals (Sweden)

    Rao Sanjay


    Full Text Available Aim/Background : Airway anomalies are infrequent but potentially life threatening in children. A program to care for these difficult children was set up at our institution, and this paper summarizes our experience. Methods: A total of 34 children were enrolled in the program over a period of three years. These children were evaluated as per the standard protocols. Treatment was individualized. Results: Of these 34 children, 28 had their airways restored and are doing well. Four children continue to remain on tracheostomy and two will require long term tracheostomy. There were two deaths. All children are under surveillance as there is a risk of recurrence. Conclusions: Airway anomalies are complex problems with significant morbidity and mortality. Current therapeutic modalities allow for good results. Most children were successfully decannulated and did well.

  18. Paediatric airway management: basic aspects

    DEFF Research Database (Denmark)

    Holm-Knudsen, R J; Rasmussen, L S


    . Airway obstruction can be avoided by paying close attention to the positioning of the head of the child and by keeping the mouth of the child open during mask ventilation. The use of oral and nasopharyngeal airways, laryngeal mask airways, and cuffed endotracheal tubes is discussed with special reference...... to the circumstances in infants. A slightly different technique during laryngoscopy is suggested. The treatment of airway oedema and laryngospasm is described....

  19. Airway epithelial cell responses to ozone injury

    Energy Technology Data Exchange (ETDEWEB)

    Leikauf, G.D.; Simpson, L.G.; Zhao, Qiyu [Univ. of Cincinnati Medical Center, OH (United States)] [and others


    The airway epithelial cell is an important target in ozone injury. Once activated, the airway epithelium responds in three phases. The initial, or immediate phase, involves activation of constitutive cells, often through direct covalent interactions including the formation of secondary ozonolysis products-hydroxyhydroperoxides, aldehydes, and hydrogen peroxide. Recently, we found hydroxyhydroperoxides to be potent agonists; of bioactive eicosanoid formation by human airway epithelial cells in culture. Other probable immediate events include activation and inactivation of enzymes present on the epithelial surface (e.g., neutral endopeptidase). During the next 2 to 24 hr, or early phase, epithelial cells respond by synthesis and release of chemotactic factors, including chemokines-macrophage inflammatory protein-2, RANTES, and interleukin-8. Infiltrating leukocytes during this period also release elastase, an important agonist of epithelial cell mucus secretion and additional chemokine formation. The third (late) phase of ozone injury is characterized by eosinophil or monocyte infiltration. Cytokine expression leads to alteration of structural protein synthesis, with increases in fibronectin evident by in situ hybridization. Synthesis of epithelial antiproteases, e.g., secretary leukocyte protease inhibitor, may also increase locally 24 to 48 hr after elastase concentrations become excessive. Thus, the epithelium is not merely a passive barrier to ozone injury but has a dynamic role in directing the migration, activating, and then counteracting inflammatory cells. Through these complex interactions, epithelial cells can be viewed as the initiators (alpha) and the receptors (omega) of ozone-induced airway disease. 51 refs., 2 figs., 3 tabs.

  20. Differential expression and function of breast regression protein 39 (BRP-39 in murine models of subacute cigarette smoke exposure and allergic airway inflammation

    Directory of Open Access Journals (Sweden)

    Coyle Anthony J


    Full Text Available Abstract Background While the presence of the chitinase-like molecule YKL40 has been reported in COPD and asthma, its relevance to inflammatory processes elicited by cigarette smoke and common environmental allergens, such as house dust mite (HDM, is not well understood. The objective of the current study was to assess expression and function of BRP-39, the murine equivalent of YKL40 in a murine model of cigarette smoke-induced inflammation and contrast expression and function to a model of HDM-induced allergic airway inflammation. Methods CD1, C57BL/6, and BALB/c mice were room air- or cigarette smoke-exposed for 4 days in a whole-body exposure system. In separate experiments, BALB/c mice were challenged with HDM extract once a day for 10 days. BRP-39 was assessed by ELISA and immunohistochemistry. IL-13, IL-1R1, IL-18, and BRP-39 knock out (KO mice were utilized to assess the mechanism and relevance of BRP-39 in cigarette smoke- and HDM-induced airway inflammation. Results Cigarette smoke exposure elicited a robust induction of BRP-39 but not the catalytically active chitinase, AMCase, in lung epithelial cells and alveolar macrophages of all mouse strains tested. Both BRP-39 and AMCase were increased in lung tissue after HDM exposure. Examining smoke-exposed IL-1R1, IL-18, and IL-13 deficient mice, BRP-39 induction was found to be IL-1 and not IL-18 or IL-13 dependent, while induction of BRP-39 by HDM was independent of IL-1 and IL-13. Despite the importance of BRP-39 in cellular inflammation in HDM-induced airway inflammation, BRP-39 was found to be redundant for cigarette smoke-induced airway inflammation and the adjuvant properties of cigarette smoke. Conclusions These data highlight the contrast between the importance of BRP-39 in HDM- and cigarette smoke-induced inflammation. While functionally important in HDM-induced inflammation, BRP-39 is a biomarker of cigarette smoke induced inflammation which is the byproduct of an IL-1

  1. Phosphine oxide surfactants revisited. (United States)

    Stubenrauch, Cosima; Preisig, Natalie; Laughlin, Robert G


    This review summarizes everything we currently know about the nonionic surfactants alkyl dimethyl (C(n)DMPO) and alkyl diethyl (C(n)DEPO) phosphine oxide (PO surfactants). The review starts with the synthesis and the general properties (Section 2) of these compounds and continues with their interfacial properties (Section 3) such as surface tension, surface rheology, interfacial tension and adsorption at solid surfaces. We discuss studies on thin liquid films and foams stabilized by PO surfactants (Section 4) as well as studies on their self-assembly into lyotropic liquid crystals and microemulsions, respectively (Section 5). We aim at encouraging colleagues from both academia and industry to take on board PO surfactants whenever possible and feasible because of their broad variety of excellent properties.

  2. 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.

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

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


    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.

  4. [Effects of once-daily low-dose administration of sustained-release theophylline on airway inflammation and airway hyperresponsiveness in patients with asthma]. (United States)

    Terao, Ichiro


    Bronchial asthma is eosinophilic airway inflammation with enhanced airway responsiveness induced by eosinophilic granule proteins such as eosinophilic cationic protein (ECP) that are released from eosinophils. In the present study using 30 outpatients with mild to moderate asthma who had no history of treatment with steroid inhalation, we examined the effects of 4-week low-dose (200 mg/day) treatment with Uniphyl Tablets, a sustained-release theophylline formulated for once-daily dosing, on airway inflammation and airway hyperresponsiveness, as well as on respiratory function. Uniphyl Tablets significantly (p statistically significant (p V50 also showed statistically significant (p < 0.05) improvement. Mean blood theophylline concentration at the time the improvements were seen was 3.95 mg/mL. These results suggest that low-dose administration of Uniphyl Tablets has anti-airway inflammatory and anti-airway hyperresponsiveness effects in mild to moderate asthmatic patients.

  5. Distinct PKA and Epac compartmentalization in airway function and plasticity

    NARCIS (Netherlands)

    Dekkers, Bart G. J.; Racke, Kurt; Schmidt, Martina


    Asthma and chronic obstructive pulmonary disease (COPD) are obstructive lung diseases characterized by airway obstruction, airway inflammation and airway remodelling. Next to inflammatory cells and airway epithelial cells, airway mesenchymal cells, including airway smooth muscle cells and (myo)fibro

  6. Surfactants and the Mechanics of Respiration (United States)

    Jbaily, Abdulrahman; Szeri, Andrew J.


    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.

  7. Airways microbiota: Hidden Trojan horses in asbestos exposed individuals? (United States)

    Magouliotis, Dimitrios E; Tasiopoulou, Vasiliki S; Molyvdas, Paschalis-Adam; Gourgoulianis, Konstantinos I; Hatzoglou, Chrissi; Zarogiannis, Sotirios G


    Malignant pleura mesothelioma (MPM) is a rare type of cancer with devastating prognosis, which develops in the pleural cavity from transformed mesothelium. MPM has been directly associated with asbestos exposure however there are aspects of the pathophysiology involved in the translocation of asbestos fibers in the pleura that remain unclear. Here, we propose and discuss that certain proteins secreted by airways symbiotic microbiota create membrane pores to the airway epithelial cells, through which asbestos fibers can penetrate the lung parenchyma and reach the sub-pleural areas. We evaluate this hypothesis using data from the published literature regarding the airways microbiota toxins such as cholesterol-dependent cytolysins (CDCs).

  8. Airway management and morbid obesity

    DEFF Research Database (Denmark)

    Kristensen, Michael S


    airway and the function of the lungs (decreased residual capacity and aggravated ventilation perfusion mismatch) worse than in lean patients. Proper planning and preparation of airway management is essential, including elevation of the patient's upper body, head and neck. Preoxygenation is mandatory...... solely on whether morbid obesity is present or not. It is important to ensure sufficient depth of anaesthesia before initiating manipulation of the airway because inadequate anaesthesia depth predisposes to aspiration if airway management becomes difficult. The intubating laryngeal mask airway is more...... pressure, noninvasive ventilation and physiotherapy....

  9. Application of peptide gemini surfactants as novel solubilization surfactants for photosystems I and II of cyanobacteria. (United States)

    Koeda, Shuhei; Umezaki, Katsunari; Noji, Tomoyasu; Ikeda, Atsushi; Kawakami, Keisuke; Kondo, Masaharu; Yamamoto, Yasushi; Shen, Jian-Ren; Taga, Keijiro; Dewa, Takehisa; Ito, Shigeru; Nango, Mamoru; Tanaka, Toshiki; Mizuno, Toshihisa


    We designed novel peptide gemini surfactants (PG-surfactants), DKDKC12K and DKDKC12D, which can solubilize Photosystem I (PSI) of Thermosynecoccus elongatus and Photosystem II (PSII) of Thermosynecoccus vulcanus in an aqueous buffer solution. To assess the detailed effects of PG-surfactants on the original supramolecular membrane protein complexes and functions of PSI and PSII, we applied the surfactant exchange method to the isolated PSI and PSII. Spectroscopic properties, light-induced electron transfer activity, and dynamic light scattering measurements showed that PSI and PSII could be solubilized not only with retention of the original supramolecular protein complexes and functions but also without forming aggregates. Furthermore, measurement of the lifetime of light-induced charge-separation state in PSI revealed that both surfactants, especially DKDKC12D, displayed slight improvement against thermal denaturation below 60 °C compared with that using β-DDM. This degree of improvement in thermal resistance still seems low, implying that the peptide moieties did not interact directly with membrane protein surfaces. By conjugating an electron mediator such as methyl viologen (MV(2+)) to DKDKC12K (denoted MV-DKDKC12K), we obtained derivatives that can trap the generated reductive electrons from the light-irradiated PSI. After immobilization onto an indium tin oxide electrode, a cathodic photocurrent from the electrode to the PSI/MV-DKDKC12K conjugate was observed in response to the interval of light irradiation. These findings indicate that the PG-surfactants DKDKC12K and DKDKC12D provide not only a new class of solubilization surfactants but also insights into designing other derivatives that confer new functions on PSI and PSII.

  10. 2-DE using hemi-fluorinated surfactants. (United States)

    Starita-Geribaldi, Mireille; Thebault, Pascal; Taffin de Givenchy, Elisabeth; Guittard, Frederic; Geribaldi, Serge


    The synthesis of hemi-fluorinated zwitterionic surfactants was realized and assessed for 2-DE, a powerful separation method for proteomic analysis. These new fluorinated amidosulfobetaine (FASB-p,m) were compared to their hydrocarbon counterparts amidosulfobetaine (ASB-n) characterized by a hydrophilic polar head, a hydrophobic and lipophilic tail, and an amido group as connector. The tail of these FASB surfactants was in part fluorinated resulting in the modulation of its lipophilicity (or oleophobicity). Their effect on the red blood cell (RBC) membrane showed a specific solubilization depending on the length of the hydrophobic part. A large number of polypeptide spots appeared in the 2-DE patterns by using FASB-p,m. The oleophobic character of these surfactants was confirmed by the fact that Band 3, a highly hydrophobic transmembrane protein, was not solubilized by these fluorinated structures. The corresponding pellet was very rich in Band 3 and could then be solubilized by using a strong detergent such as amidosulfobetaine with an alkyl tail containing 14 carbon atoms (ASB-14). Thus, these hemi-fluorinated surfactants appeared as powerful tools when used at the first step of a two-step solubilization strategy using a hydrocarbon homologous surfactant in the second step.

  11. Advances in prehospital airway management. (United States)

    Jacobs, Pe; Grabinsky, A


    Prehospital airway management is a key component of emergency responders and remains an important task of Emergency Medical Service (EMS) systems worldwide. The most advanced airway management techniques involving placement of oropharyngeal airways such as the Laryngeal Mask Airway or endotracheal tube. Endotracheal tube placement success is a common measure of out-of-hospital airway management quality. Regional variation in regard to training, education, and procedural exposure may be the major contributor to the findings in success and patient outcome. In studies demonstrating poor outcomes related to prehospital-attempted endotracheal intubation (ETI), both training and skill level of the provider are usually often low. Research supports a relationship between the number of intubation experiences and ETI success. National standards for certification of emergency medicine provider are in general too low to guarantee good success rate in emergency airway management by paramedics and physicians. Some paramedic training programs require more intense airway training above the national standard and some EMS systems in Europe staff their system with anesthesia providers instead. ETI remains the cornerstone of definitive prehospital airway management, However, ETI is not without risk and outcomes data remains controversial. Many systems may benefit from more input and guidance by the anesthesia department, which have higher volumes of airway management procedures and extensive training and experience not just with training of airway management but also with different airway management techniques and adjuncts.

  12. Surfactant-Amino Acid and Surfactant-Surfactant Interactions in Aqueous Medium: a Review. (United States)

    Malik, Nisar Ahmad


    An overview of surfactant-amino acid interactions mainly in aqueous medium has been discussed. Main emphasis has been on the solution thermodynamics and solute-solvent interactions. Almost all available data on the topic has been presented in a lucid and simple way. Conventional surfactants have been discussed as amphiphiles forming micelles and amino acids as additives and their effect on the various physicochemical properties of these conventional surfactants. Surfactant-surfactant interactions in aqueous medium, various mixed surfactant models, are also highlighted to assess their interactions in aqueous medium. Finally, their applied part has been taken into consideration to interpret their possible uses.

  13. Zinc supplementation alters airway inflammation and airway hyperresponsiveness to a common allergen

    Directory of Open Access Journals (Sweden)

    Morgan Carrie I


    Full Text Available Abstract Background Zinc supplementation can modulate immunity through inhibition of NF-κB, a transcription factor that controls many immune response genes. Thus, we sought to examine the mechanism by which zinc supplementation tempers the response to a common allergen and determine its effect on allergic airway inflammation. Methods Mice were injected with zinc gluconate prior to German cockroach (GC feces (frass exposure and airway inflammation was assessed. Primary bone marrow-derived neutrophils and DMSO-differentiated HL-60 cells were used to assess the role of zinc gluconate on tumor necrosis factor (TNFα expression. NF-κB:DNA binding and IKK activity were assessed by EMSA and in vitro kinase assay. Protein levels of A20, RIP1 and TRAF6 were assessed by Western blot analysis. Establishment of allergic airway inflammation with GC frass was followed by administration of zinc gluconate. Airway hyperresponsiveness, serum IgE levels, eosinophilia and Th2 cytokine production were assessed. Results Administration of zinc gluconate prior to allergen exposure resulted in significantly decreased neutrophil infiltration and TNFα cytokine release into the airways. This correlated with decreased NF-κB activity in the whole lung. Treatment with zinc gluconate significantly decreased GC frass-mediated TNFα production from bone-marrow derived neutrophils and HL-60 cells. We confirmed zinc-mediated decreases in NF-κB:DNA binding and IKK activity in HL-60 cells. A20, a natural inhibitor of NF-κB and a zinc-fingered protein, is a potential target of zinc. Zinc treatment did not alter A20 levels in the short term, but resulted in the degradation of RIP1, an important upstream activator of IKK. TRAF6 protein levels were unaffected. To determine the application for zinc as a therapeutic for asthma, we administered zinc following the establishment of allergic airway inflammation in a murine model. Zinc supplementation decreased airway hyperresponsiveness

  14. Upper airway imaging and its role in preoperative airway evaluation

    Directory of Open Access Journals (Sweden)

    Jagadish G Sutagatti


    Full Text Available Ultrasonography (USG is well-known as a fast, safe, and noninvasive technique. Its application for imaging of the airway is now gaining momentum. The upper airway has a complex anatomy, and its assessment forms a vital part of every preanesthetic evaluation. Ultrasound (US imaging can help in upper airway assessment in the preoperative period. There are various approaches to upper airway USG. The technique has its own advantages, disadvantages, and limitations. This simple yet challenging imaging technique is all set to become an important part of routine preoperative airway evaluation. This article reviews the various approaches to upper airway US imaging, interpretation of the images, limitations, and disadvantages of the technique and its varied clinical applications in the preoperative period. The scientific material presented here was hand searched from textbooks and journals, electronically from PubMed, and Google scholar using text words.

  15. Relationship between airway pathophysiology and airway inflammation in older asthmatics

    DEFF Research Database (Denmark)

    Porsbjerg, Celeste M; Gibson, Peter G; Pretto, Jeffrey J;


    BACKGROUND AND OBJECTIVE: Asthma-related morbidity is greater in older compared with younger asthmatics. Airway closure is also greater in older asthmatics, an observation that may be explained by differences in airway inflammation. We hypothesized that in older adult patients with asthma......: Mean patient age was 67 years (confidence interval: 63-71) with a mean FEV1 of 78 % predicted (confidence interval: 70-85%). AHR correlated with sputum eosinophils (r = 0.68, P = 0.005) and eNO (r = 0.71, P ... or eNO. CONCLUSIONS: In older patients with asthma, airway inflammatory cells are linked to abnormal airway physiology. Eosinophilic airway inflammation is associated with AHR while neutrophilic inflammation may be an important determinant of airflow limitation at rest and airway closure during...

  16. Integrated care pathways for airway diseases (AIRWAYS-ICPs)

    DEFF Research Database (Denmark)

    Bousquet, J; Addis, A; Adcock, I


    The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy....... AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers)....

  17. Ultrasound of the airway

    Directory of Open Access Journals (Sweden)

    Pankaj Kundra


    Full Text Available Currently, the role of ultrasound (US in anaesthesia-related airway assessment and procedural interventions is encouraging, though it is still ill defined. US can visualise anatomical structures in the supraglottic, glottic and subglottic regions. The floor of the mouth can be visualised by both transcutaneous view of the neck and also by transoral or sublinguial views. However, imaging the epiglottis can be challenging as it is suspended in air. US may detect signs suggestive of difficult intubation, but the data are limited. Other possible applications in airway management include confirmation of correct endotracheal tube placement, prediction of post-extubation stridor, evaluation of soft tissue masses in the neck prior to intubation, assessment of subglottic diameter for determination of paediatric endotracheal tube size and percutaneous dilatational tracheostomy. With development of better probes, high-resolution imaging, real-time picture and clinical experience, US has become the potential first-line noninvasive airway assessment tool in anaesthesia and intensive care practice.

  18. Fibrinogen stability under surfactant interaction. (United States)

    Hassan, Natalia; Barbosa, Leandro R S; Itri, Rosangela; Ruso, Juan M


    Differential scanning calorimetry (DSC), circular dichroism (CD), difference spectroscopy (UV-vis), Raman spectroscopy, and small-angle X-ray scattering (SAXS) measurements have been performed in the present work to provide a quantitatively comprehensive physicochemical description of the complexation between bovine fibrinogen and the sodium perfluorooctanoate, sodium octanoate, and sodium dodecanoate in glycine buffer (pH 8.5). It has been found that sodium octanoate and dodecanoate act as fibrinogen destabilizer. Meanwhile, sodium perfluorooctanoate acts as a structure stabilizer at low molar concentration and as a destabilizer at high molar concentration. Fibrinogen's secondary structure is affected by all three studied surfactants (decrease in α-helix and an increase in β-sheet content) to a different extent. DSC and UV-vis revealed the existence of intermediate states in the thermal unfolding process of fibrinogen. In addition, SAXS data analysis showed that pure fibrinogen adopts a paired-dimer structure in solution. Such a structure is unaltered by sodium octanoate and perfluoroctanoate. However, interaction of sodium dodecanoate with the fibrinogen affects the protein conformation leading to a complex formation. Taken together, all results evidence that both surfactant hydrophobicity and tail length mediate the fibrinogen stability upon interaction.

  19. Anticholinergic treatment in airways diseases.

    LENUS (Irish Health Repository)

    Flynn, Robert A


    The prevalence of chronic airways diseases such as chronic obstructive pulmonary disease and asthma is increasing. They lead to symptoms such as a cough and shortness of breath, partially through bronchoconstriction. Inhaled anticholinergics are one of a number of treatments designed to treat bronchoconstriction in airways disease. Both short-acting and long-acting agents are now available and this review highlights their efficacy and adverse event profile in chronic airways diseases.

  20. Airway epithelium is a predominant source of endogenous airway GABA and contributes to relaxation of airway smooth muscle tone


    Gallos, George; Townsend, Elizabeth; Yim, Peter; Virag, Laszlo; Zhang, Yi; Xu, Dingbang; Bacchetta, Matthew; Emala, Charles W.


    Chronic obstructive pulmonary disease and asthma are characterized by hyperreactive airway responses that predispose patients to episodes of acute airway constriction. Recent studies suggest a complex paradigm of GABAergic signaling in airways that involves GABA-mediated relaxation of airway smooth muscle. However, the cellular source of airway GABA and mechanisms regulating its release remain unknown. We questioned whether epithelium is a major source of GABA in the airway and whether the ab...

  1. Hypoxia-inducible factor 2α plays a critical role in the formation of alveoli and surfactant

    NARCIS (Netherlands)

    Y. Huang (Yao); M. Buscop-Van Kempen (Marjon); A. de Munck (Anne); S.M.A. Swagemakers (Sigrid); M.J.F. Driegen (Siska); P. Mahavadi (Poornima); D.N. Meijer (Dies); W.F.J. van IJcken (Wilfred); P.J. van der Spek (Peter); F.G. Grosveld (Frank); A. Günther (Andreas); D. Tibboel (Dick); R.J. Rottier (Robbert)


    textabstractAlveolarization of the developing lung is an important step toward the switch from intrauterine life to breathing oxygen-rich air after birth. The distal airways structurally change to minimize the gas exchange path, and Type II pneumocytes increase the production of surfactants, which a

  2. Effect of curcumin on the binding of cationic, anionic and nonionic surfactants with myoglobin (United States)

    Mondal, Satyajit; Ghosh, Soumen


    Interaction of a globular protein, myoglobin and different surfactants has been studied in the absence and presence of curcumin in phosphate buffer at pH = 7.4 by UV-VIS spectrophotometry, fluorimetry and fluorescence polarization anisotropy methods. Results show that heme environment of myoglobin is changed by cationic cetyltrimethylammonium bromide (CTAB) and sodium N-dodecanoyl sarcosinate (SDDS). In the presence of curcumin, CTAB cannot change the heme; but SDDS can make change. Nonionic surfactant N-decanoyl-N-methylglucamine (Mega 10) cannot change the heme environment. Protein is unfolded by the surfactant. Curcumin can prevent the unfolding of protein in the low concentration region of ionic surfactants such as CTAB and SDDS. In nonionic surfactant media, curcumin accelerates the denaturation process. Due to myoglobin-curcumin complex formation, rotational motion of curcumin decreases in surfactant media and so anisotropy increases.

  3. Sizing up surfactant synthesis. (United States)

    Han, SeungHye; Mallampalli, Rama K


    Phosphatidylcholine is generated through de novo synthesis and remodeling involving a lysophospholipid. In this issue of Cell Metabolism, research from the Shimizu lab (Harayama et al., 2014) demonstrates the highly selective enzymatic behavior of lysophospholipid acyltransferases. The authors present an enzymatic model for phosphatidylcholine molecular species diversification that impacts surfactant formation.

  4. Surfactant and adhesive formulations from alkaline biomass extracts (United States)

    Baxter, Matthew

    This work studies the ability to produce effective surfactant and adhesive formulations using surface active biological material extracted from different biomass sources using alkaline extraction methods. Two urban waste biomass sources were used to produce surfactants, Return Activated Sludge (RAS), and solid Urban Refuse (UR). The third biomass source investigated was isolated mustard protein (MP). RAS and MP extracts were investigated for adhesive production. The results indicate that extracts from the waste biomass sources, RAS and UR, can be combined with a commercial surfactant, sodium dioctyl sulfosuccinate (AOT), to produce surfactants with low interfacial tensions against various oils. These highly surface-active formulations were shown to be useful in the removal of bitumen from contaminated sand. RAS and MP showed potential as protein-based wood adhesives. These sources were used in adhesive formulations to produce a strong bond strength under low-pressure, ambient pressing conditions.

  5. Pharmacology of airway smooth muscle proliferation

    NARCIS (Netherlands)

    Gosens, Reinoud; Roscioni, Sara S.; Dekkers, Bart G. J.; Pera, Tonio; Schmidt, Martina; Schaafsma, Dedmer; Zaagsma, Johan; Meurs, Herman


    Airway smooth muscle thickening is a pathological feature that contributes significantly to airflow limitation and airway hyperresponsiveness in asthma. Ongoing research efforts aimed at identifying the mechanisms responsible for the increased airway smooth muscle mass have indicated that hyperplasi

  6. Cholinergic regulation of airway inflammation and remodelling

    NARCIS (Netherlands)

    Kolahian, Saeed; Gosens, Reinoud


    Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway disease

  7. Airway inflammation in Japanese COPD patients compared with smoking and nonsmoking controls

    Directory of Open Access Journals (Sweden)

    Ishikawa N


    Full Text Available Nobuhisa Ishikawa,1 Noboru Hattori,2 Nobuoki Kohno,2 Akihiro Kobayashi,3 Tomoyuki Hayamizu,4 Malcolm Johnson5 1Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan; 2Department of Molecular and Internal Medicine, Hiroshima University, Hiroshima, Japan; 3Biomedical Data Science Department, 4Medical Affairs Respiratory Department, GlaxoSmithKline Shibuya-ku, Tokyo, Japan; 5Respiratory Global Franchise, GlaxoSmithKline, Uxbridge, UK Purpose: To assess the importance of inflammation in chronic obstructive pulmonary disease (COPD by measuring airway and systemic inflammatory biomarkers in Japanese patients with the disease and relevant control groups.Patients and methods: This was the first study of its type in Japanese COPD patients. It was a non-treatment study in which 100 participants were enrolled into one of three groups: nonsmoking controls, current or ex-smoking controls, and COPD patients. All participants underwent standard lung function assessments and provided sputum and blood samples from which the numbers of inflammatory cells and concentrations of biomarkers were measured, using standard procedures.Results: The overall trends observed in levels of inflammatory cells and biomarkers in sputum and blood in COPD were consistent with previous reports in Western studies. Increasing levels of neutrophils, interleukin 8 (IL-8, surfactant protein D (SP-D, and Krebs von den Lungen 6 (KL-6 in sputum and clara cell 16 (CC-16, high-sensitivity C-reactive protein (hs-CRP, and KL-6 in serum and plasma fibrinogen were seen in the Japanese COPD patients compared with the non-COPD control participants. In sputum, significant correlations were seen between total cell count and matrix metalloproteinase 9 (MMP-9; P<0.001, neutrophils and MMP-9 (P<0.001, macrophages and KL-6 (P<0.01, total cell count and IL-8 (P<0.05, neutrophils and IL-8 (P<0.05, and macrophages and MMP-9 (P<0.05. Significant correlations were also

  8. The Role of Surfactant in Lung Disease and Host Defense against Pulmonary Infections. (United States)

    Han, SeungHye; Mallampalli, Rama K


    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.

  9. Biophysical activity of animal-derived exogenous surfactants mixed with rifampicin. (United States)

    Kolomaznik, M; Calkovska, A; Herting, E; Stichtenoth, G


    Exogenous pulmonary surfactant is a potential delivery system for topical medications via the conducting airways. Due to the sensitivity to inactivation of surfactant, mutual interaction with the shipped drug should be evaluated. Little is known about the interactions between surfactant and antimicrobial drugs. The aim of the present study was to evaluate whether biophysical properties of animal-derived surfactants are modified by the bactericidal antibiotic rifampicin. An intracellular activity and a broad antimicrobiotic spectrum toward Gram-negative and Gram-positive bacteria make rifampicin an interesting substance against pulmonary infections. Curosurf® (porcine surfactant from minced lungs) and Survanta® (bovine surfactant extract) were diluted to 2.5-5.0 mg/ml of phospholipids in 0.9 % NaCl and rifampicin (RIF) was added at 1, 5, and 10 % (w/w). Minimum (γ(min)) and maximum (γ(max)) surface tension of a cyclically compressed bubble in the mixture was assessed with a pulsating bubble surfactometer. After 5 min, γ(min) of Survanta at a concentration of 3 mg/ml was significantly increased after addition of 5 and 10 % RIF (both p surfactant is able to retain good surface activity when mixed with antibiotics.

  10. Early administration of the second surfactant dose in preterm infants with severe respiratory distress syndrome. (United States)

    Köksal, Nilgün; Akpinar, Reyhan; Cetinkaya, Merih


    The aim of this study was to determine whether early administration (2 hours after the first surfactant dose) of the second surfactant dose would be superior to late surfactant treatment (6 hours after the first surfactant dose) in preterm infants with severe respiratory distress syndrome. Between June 2003 and March 2005, 40 newborns born with respiratory distress syndrome in Uludağ University Hospital were investigated in this prospective study. The inclusion criteria for the recruitment of the infants were: age respiratory distress syndrome, and need for mechanical ventilation with inspiratory oxygen fraction > or = 0.4 and mean airway pressure > or = 7 cm H2O to obtain arterial pressure of oxygen between 70-80 mmHg. Infants with lethal congenital anomalies or being treated with high-frequency oscillatory ventilation were excluded from the study. Birth weight, gestational age, gender, and Apgar scores were recorded and complications of the surfactant therapy were examined. Twenty boys and 20 girls were enrolled in the study. The first surfactant dose was administered in the first hour of life in all infants. The second surfactant dose was given 2 hours after the first dose in 20 of them and 6 hours after the first dose in the other 20. Infants in both groups (early versus late) were similar with respect to gestational age, birth weight, gender, and the rate of prenatal corticosteroids. There were also no significant differences between the two groups in terms of the response to surfactant therapy and complications. The results of this study show that administration of the second surfactant dose earlier is as effective as late administration, and it may be suggested that the second surfactant dose can be applied earlier in severe respiratory distress syndrome.

  11. Evaluation and management of inherited disorders of surfactant metabolism

    Institute of Scientific and Technical Information of China (English)

    Aaron Hamvas


    Objective To review the pathophysiology, evaluation, management, and outcomes of children with inherited disorders of surfactant metabolism due to mutations in the genes encoding surfactant proteins-B or -C(SFTPB, SFTPC), ATP binding cassette member A3 (ABCA3), and thyroid transcription factor (NKX2.1).Data sources Review of the literature, previous work from the author's and collaborators' laboratories, St. Louis Children's Hospital Lung Transplant Database.Study selection Key articles in the field, author's work.Results Inherited disorders of surfactant metabolism present as acute, severe respiratory dysfunction in the neonatal period (SFTPB, ABCA3, NKX2.1) or as chronic respiratory insufficiency in later infancy and childhood which is of variable onset, severity, and course (SFTPC, ABCA3, NKX2.1). Diagnosis is established with sequencing the relevant genes; lung biopsy with electron microscopy is a useful adjunct. For surfactant protein-B and ABCA3 deficiency presenting with acute neonatal disease, treatment options are limited to lung transplantation or compassionate care. For the more chronic presentations of surfactant protein-C, ABCA3, and NKX2.1 associated disease, the natural history is variable and therefore individualized, supportive care is appropriate,Conclusions Inherited disorders of surfactant metabolism are rare, but informative diseases that provide unique opportunities for understanding mechanisms of respiratory disease in newborns and children.

  12. Biophysical inhibition of synthetic vs. naturally-derived pulmonary surfactant preparations by polymeric nanoparticles. (United States)

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


    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.

  13. Muscarinic receptors on airway mesenchymal cells : Novel findings for an ancient target

    NARCIS (Netherlands)

    Meurs, Herman; Dekkers, Bart G. J.; Maarsingh, Harm; Halayko, Andrew J.; Zaagsma, Johan; Gosens, Reinoud


    Since ancient times, anticholinergics have been used as a bronchodilator therapy for obstructive lung diseases. Targets of these drugs are G-protein-coupled muscarinic M-1, M-2 and M-3 receptors in the airways, which have long been recognized to regulate vagally-induced airway smooth muscle contract

  14. Mechanisms of Cigarette Smoke Effects on Human Airway Smooth Muscle.

    Directory of Open Access Journals (Sweden)

    Mark E Wylam

    Full Text Available Cigarette smoke contributes to or exacerbates airway diseases such as asthma and COPD, where airway hyperresponsiveness and airway smooth muscle (ASM proliferation are key features. While factors such as inflammation contribute to asthma in part by enhancing agonist-induced intracellular Ca(2+ ([Ca(2+]i responses of ASM, the mechanisms by which cigarette smoke affect ASM are still under investigation. In the present study, we tested the hypothesis that cigarette smoke enhances the expression and function of Ca(2+ regulatory proteins leading to increased store operated Ca(2+ entry (SOCE and cell proliferation. Using isolated human ASM (hASM cells, incubated in the presence and absence cigarette smoke extract (CSE we determined ([Ca(2+]i responses and expression of relevant proteins as well as ASM proliferation, reactive oxidant species (ROS and cytokine generation. CSE enhanced [Ca(2+]i responses to agonist and SOCE: effects mediated by increased expression of TRPC3, CD38, STIM1, and/or Orai1, evident by attenuation of CSE effects when siRNAs against these proteins were used, particularly Orai1. CSE also increased hASM ROS generation and cytokine secretion. In addition, we found in the airways of patients with long-term smoking history, TRPC3 and CD38 expression were significantly increased compared to life-long never-smokers, supporting the role of these proteins in smoking effects. Finally, CSE enhanced hASM proliferation, an effect confirmed by upregulation of PCNA and Cyclin E. These results support a critical role for Ca(2+ regulatory proteins and enhanced SOCE to alter airway structure and function in smoking-related airway disease.


    Directory of Open Access Journals (Sweden)

    T. P. Pirog


    Full Text Available The classification and the chemical structure of the lipopeptides and their producers (bacteria of the genera Bacillus and Pseudomonas are given. The role of the lipopeptides in cells motility, biofilm formation, metal binding and xenobiotics degradation and their action on the cells of pro- and eukaryotes is summarized. The stages of the nonribosomal lipopeptides synthesis and the role of two-component (GacA/GacS, ComA/ComP and the quorum system regulation of this process are shown. The potential of lactic acid bacteria and marine microorganisms as alternative surfactants producers (glycolipids, lipopeptides, phospholipids and fatty acids, glycolipopeptides are discussed. Their productivity and advantages over traditional producers are given as well. The properties of surfactants synthesized by lactic acid bacteria (the reduction of the surface tension, the critical micelle concentration, the stability in a wide range of pH, the temperature, the biological activity are summarized. Surfactants of nonpathogenic probiotic bacteria could be used as effective antimicrobial agents and antiadhesive and marine producers which able to synthesize unique metabolites that are not produced by other microorganisms.

  16. Exon B of human surfactant protein A2 mRNA, alone or within its surrounding sequences, interacts with 14-3-3; role of cis-elements and secondary structure. (United States)

    Noutsios, Georgios T; Silveyra, Patricia; Bhatti, Faizah; Floros, Joanna


    Human surfactant protein A, an innate immunity molecule, is encoded by two genes: SFTPA1 (SP-A1) and SFTPA2 (SP-A2). The 5' untranslated (5'UTR) splice variant of SP-A2 (ABD), but not of SP-A1 (AD), contains exon B (eB), which is an enhancer for transcription and translation. We investigated whether eB contains cis-regulatory elements that bind trans-acting factors in a sequence-specific manner as well as the role of the eB mRNA secondary structure. Binding of cytoplasmic NCI-H441 proteins to wild-type eB, eB mutant, AD, and ABD 5'UTR mRNAs were studied by RNA electromobility shift assays (REMSAs). The bound proteins were identified by mass spectroscopy and specific antibodies (Abs). We found that 1) proteins bind eB mRNA in a sequence-specific manner, with two cis-elements identified within eB to be important; 2) eB secondary structure is necessary for binding; 3) mass spectroscopy and specific Abs in REMSAs identified 14-3-3 proteins to bind (directly or indirectly) eB and the natural SP-A2 (ABD) splice variant but not the SP-A1 (AD) splice variant; 4) other ribosomal and cytoskeletal proteins, and translation factors, are also present in the eB mRNA-protein complex; 5) knockdown of 14-3-3 β/α isoform resulted in a downregulation of SP-A2 expression. In conclusion, proteins including the 14-3-3 family bind two cis-elements within eB of hSP-A2 mRNA in a sequence- and secondary structure-specific manner. Differential regulation of SP-A1 and SP-A2 is mediated by the 14-3-3 protein family as well as by a number of other proteins that bind UTRs with or without eB mRNA.

  17. Surfactants at the Design Limit. (United States)

    Czajka, Adam; Hazell, Gavin; Eastoe, Julian


    This article analyzes how the individual structural elements of surfactant molecules affect surface properties, in particular, the point of reference defined by the limiting surface tension at the aqueous cmc, γcmc. Particular emphasis is given to how the chemical nature and structure of the hydrophobic tails influence γcmc. By comparing the three different classes of surfactants, fluorocarbon, silicone, and hydrocarbon, a generalized surface packing index is introduced which is independent of the chemical nature of the surfactants. This parameter ϕcmc represents the volume fraction of surfactant chain fragments in a surface film at the aqueous cmc. It is shown that ϕcmc is a useful index for understanding the limiting surface tension of surfactants and can be useful for designing new superefficient surfactants.

  18. 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


    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.

  19. Knockdown of flotillin-2 inhibits lung surfactant secretion by alveolar type Ⅱ cells

    Institute of Scientific and Technical Information of China (English)

    Narendranath Reddy Chintagari; Deming Gou; Lin Liu


    @@ Dear Editor, Lung surfactant is stored in lamellar bodies and exocytosed following fusion of the lamellar bodies with the plasma membrane of alveolar type Ⅱ (AT2) cells [1].A number of proteins have been shown to be involved in surfactant secretion including SNAREs,NSF,α-SNAP and annexin A2 [2,3].Lipid rafts enriched in SNAREs are crucial for surfactant secretion [4].

  20. Ambroxol suppresses influenza-virus proliferation in the mouse airway by increasing antiviral factor levels. (United States)

    Yang, B; Yao, D F; Ohuchi, M; Ide, M; Yano, M; Okumura, Y; Kido, H


    The protective effect of ambroxol, a mucolytic agent which has antioxidant properties and stimulates the release of pulmonary surfactant, against influenza-virus proliferation in the airway was investigated in mice. Ambroxol or the vehicle was administered intraperitoneally twice a day for 5-7 days to mice shortly after intranasal infection with a lethal dose of influenza A/Aichi/68 (H3N2) virus, and the survival rate, virus titre and levels of factors regulating virus proliferation in the airway fluid were analysed. Ambroxol significantly suppressed virus multiplication and improved the survival rate of mice. The effect of ambroxol reached a peak at 10 mg x kg(-1) x day(-1), higher doses being less effective. Ambroxol stimulated the release of suppressors of influenza-virus multiplication, such as pulmonary surfactant, mucus protease inhibitor, immunoglobulin (Ig)-A and IgG, although it stimulated the release of a trypsin-type protease that potentiates virus proliferation. In addition, ambroxol transiently suppressed release of the cytokines, tumour necrosis factor-alpha, interferon-gamma and interleukin-12, into airway fluid. Although ambroxol had several negative effects on the host defence system, overall it strikingly increased the concentrations of suppressors of influenza-virus multiplication in the airway.

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

    Directory of Open Access Journals (Sweden)

    Dave Vrushank


    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.

  2. Acanthamoeba protease activity promotes allergic airway inflammation via protease-activated receptor 2. (United States)

    Park, Mi Kyung; Cho, Min Kyoung; Kang, Shin Ae; Park, Hye-Kyung; Kim, Dong-Hee; Yu, Hak Sun


    Acanthamoeba is a free-living amoeba commonly present in the environment and often found in human airway cavities. Acanthamoeba possesses strong proteases that can elicit allergic airway inflammation. To our knowledge, the aeroallergenicity of Acanthamoeba has not been reported. We repeatedly inoculated mice with Acanthamoeba trophozoites or excretory-secretory (ES) proteins intra-nasally and evaluated symptoms and airway immune responses. Acanthamoeba trophozoites or ES proteins elicited immune responses in mice that resembled allergic airway inflammation. ES proteins had strong protease activity and activated the expression of several chemokine genes (CCL11, CCL17, CCL22, TSLP, and IL-25) in mouse lung epithelial cells. The serine protease inhibitor phenyl-methane-sulfonyl fluoride (PMSF) inhibited ES protein activity. ES proteins also stimulated dendritic cells and enhanced the differentiation of naive T cells into IL-4-secreting T cells. After repeated inoculation of the protease-activated receptor 2 knockout mouse with ES proteins, airway inflammation and Th2 immune responses were markedly reduced, but not to basal levels. Furthermore, asthma patients had higher Acanthamoeba-specific IgE titers than healthy controls and we found Acanthamoeba specific antigen from house dust in typical living room. Our findings suggest that Acanthamoeba elicits allergic airway symptoms in mice via a protease allergen. In addition, it is possible that Acanthamoeba may be one of the triggers human airway allergic disease.

  3. Acanthamoeba protease activity promotes allergic airway inflammation via protease-activated receptor 2.

    Directory of Open Access Journals (Sweden)

    Mi Kyung Park

    Full Text Available Acanthamoeba is a free-living amoeba commonly present in the environment and often found in human airway cavities. Acanthamoeba possesses strong proteases that can elicit allergic airway inflammation. To our knowledge, the aeroallergenicity of Acanthamoeba has not been reported. We repeatedly inoculated mice with Acanthamoeba trophozoites or excretory-secretory (ES proteins intra-nasally and evaluated symptoms and airway immune responses. Acanthamoeba trophozoites or ES proteins elicited immune responses in mice that resembled allergic airway inflammation. ES proteins had strong protease activity and activated the expression of several chemokine genes (CCL11, CCL17, CCL22, TSLP, and IL-25 in mouse lung epithelial cells. The serine protease inhibitor phenyl-methane-sulfonyl fluoride (PMSF inhibited ES protein activity. ES proteins also stimulated dendritic cells and enhanced the differentiation of naive T cells into IL-4-secreting T cells. After repeated inoculation of the protease-activated receptor 2 knockout mouse with ES proteins, airway inflammation and Th2 immune responses were markedly reduced, but not to basal levels. Furthermore, asthma patients had higher Acanthamoeba-specific IgE titers than healthy controls and we found Acanthamoeba specific antigen from house dust in typical living room. Our findings suggest that Acanthamoeba elicits allergic airway symptoms in mice via a protease allergen. In addition, it is possible that Acanthamoeba may be one of the triggers human airway allergic disease.

  4. 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. (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


    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.

  5. Vessel-guided Airway Tree Segmentation

    DEFF Research Database (Denmark)

    Lo, P.; Sporring, J.; Ashraf, H.;


    This paper presents a method for airway tree segmentation that uses a combination of a trained airway appearance model, vessel and airway orientation information, and region growing. We propose a voxel classification approach for the appearance model, which uses a classifier that is trained...... to differentiate between airway and non-airway voxels. This is in contrast to previous works that use either intensity alone or hand crafted models of airway appearance. We show that the appearance model can be trained with a set of easily acquired, incomplete, airway tree segmentations. A vessel orientation...

  6. Bronchoconstriction Induces TGF-β Release and Airway Remodelling in Guinea Pig Lung Slices.

    Directory of Open Access Journals (Sweden)

    Tjitske A Oenema

    Full Text Available Airway remodelling, including smooth muscle remodelling, is a primary cause of airflow limitation in asthma. Recent evidence links bronchoconstriction to airway remodelling in asthma. The mechanisms involved are poorly understood. A possible player is the multifunctional cytokine TGF-β, which plays an important role in airway remodelling. Guinea pig lung slices were used as an in vitro model to investigate mechanisms involved in bronchoconstriction-induced airway remodelling. To address this aim, mechanical effects of bronchoconstricting stimuli on contractile protein expression and TGF-β release were investigated. Lung slices were viable for at least 48 h. Both methacholine and TGF-β1 augmented the expression of contractile proteins (sm-α-actin, sm-myosin, calponin after 48 h. Confocal fluorescence microscopy showed that increased sm-myosin expression was enhanced in the peripheral airways and the central airways. Mechanistic studies demonstrated that methacholine-induced bronchoconstriction mediated the release of biologically active TGF-β, which caused the increased contractile protein expression, as inhibition of actin polymerization (latrunculin A or TGF-β receptor kinase (SB431542 prevented the methacholine effects, whereas other bronchoconstricting agents (histamine and KCl mimicked the effects of methacholine. Collectively, bronchoconstriction promotes the release of TGF-β, which induces airway smooth muscle remodelling. This study shows that lung slices are a useful in vitro model to study mechanisms involved in airway remodelling.

  7. Airway complications after lung transplantation. (United States)

    Machuzak, Michael; Santacruz, Jose F; Gildea, Thomas; Murthy, Sudish C


    Airway complications after lung transplantation present a formidable challenge to the lung transplant team, ranging from mere unusual images to fatal events. The exact incidence of complications is wide-ranging depending on the type of event, and there is still evolution of a universal characterization of the airway findings. Management is also wide-ranging. Simple observation or simple balloon bronchoplasty is sufficient in many cases, but vigilance following more severe necrosis is required for late development of both anastomotic and nonanastomotic airway strictures. Furthermore, the impact of coexisting infection, rejection, and medical disease associated with high-level immunosuppression further complicates care.

  8. Airway vascular reactivity and vascularisation in human chronic airway disease

    NARCIS (Netherlands)

    Bailey, Simon R; Boustany, Sarah; Burgess, Janette K; Hirst, Stuart J; Sharma, Hari S; Simcock, David E; Suravaram, Padmini R; Weckmann, Markus


    Altered bronchial vascular reactivity and remodelling including angiogenesis are documented features of asthma and other chronic inflammatory airway diseases. Expansion of the bronchial vasculature under these conditions involves both functional (vasodilation, hyperperfusion, increased microvascular

  9. Recent advances in alveolar biology: evolution and function of alveolar proteins. (United States)

    Orgeig, Sandra; Hiemstra, Pieter S; Veldhuizen, Edwin J A; Casals, Cristina; Clark, Howard W; Haczku, Angela; Knudsen, Lars; Possmayer, Fred


    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 groups of surfactant proteins - the small molecular weight hydrophobic SPs, SP-B and -C, that regulate interfacial adsorption of the lipids, and the large hydrophilic SPs, SP-A and -D, which are surfactant collectins capable of inhibiting foreign pathogens. Further aiding pulmonary host defence are non-surfactant collectins and antimicrobial peptides that are expressed across the biological kingdoms. Linking to the first symposium session, which emphasised molecular structure and biophysical function of surfactant lipids and proteins, this review begins with a discussion of the role of temperature and hydrostatic pressure in shaping the evolution of SP-C in mammals. Transitioning to the role of the alveolus in innate host defence we discuss the structure, function and regulation of antimicrobial peptides, the defensins and cathelicidins. We describe the recent discovery of novel avian collectins and provide evidence for their role in preventing influenza infection. This is followed by discussions of the roles of SP-A and SP-D in mediating host defence at the alveolar surface and in mediating inflammation and the allergic response of the airways. Finally we discuss the use of animal models of lung disease including knockouts to develop an understanding of the role of these proteins in initiating and/or perpetuating disease with the aim of developing new therapeutic strategies.

  10. Airway Epithelium Stimulates Smooth Muscle Proliferation


    Malavia, Nikita K.; Raub, Christopher B.; Mahon, Sari B.; Brenner, Matthew; Reynold A Panettieri; George, Steven C.


    Communication between the airway epithelium and stroma is evident during embryogenesis, and both epithelial shedding and increased smooth muscle proliferation are features of airway remodeling. Hence, we hypothesized that after injury the airway epithelium could modulate airway smooth muscle proliferation. Fully differentiated primary normal human bronchial epithelial (NHBE) cells at an air–liquid interface were co-cultured with serum-deprived normal primary human airway smooth muscle cells (...

  11. Vacuolar ATPase regulates surfactant secretion in rat alveolar type II cells by modulating lamellar body calcium.

    Directory of Open Access Journals (Sweden)

    Narendranath Reddy Chintagari

    Full Text Available Lung surfactant reduces surface tension and maintains the stability of alveoli. How surfactant is released from alveolar epithelial type II cells is not fully understood. Vacuolar ATPase (V-ATPase is the enzyme responsible for pumping H(+ into lamellar bodies and is required for the processing of surfactant proteins and the packaging of surfactant lipids. However, its role in lung surfactant secretion is unknown. Proteomic analysis revealed that vacuolar ATPase (V-ATPase dominated the alveolar type II cell lipid raft proteome. Western blotting confirmed the association of V-ATPase a1 and B1/2 subunits with lipid rafts and their enrichment in lamellar bodies. The dissipation of lamellar body pH gradient by Bafilomycin A1 (Baf A1, an inhibitor of V-ATPase, increased surfactant secretion. Baf A1-stimulated secretion was blocked by the intracellular Ca(2+ chelator, BAPTA-AM, the protein kinase C (PKC inhibitor, staurosporine, and the Ca(2+/calmodulin-dependent protein kinase II (CaMKII, KN-62. Baf A1 induced Ca(2+ release from isolated lamellar bodies. Thapsigargin reduced the Baf A1-induced secretion, indicating cross-talk between lamellar body and endoplasmic reticulum Ca(2+ pools. Stimulation of type II cells with surfactant secretagogues dissipated the pH gradient across lamellar bodies and disassembled the V-ATPase complex, indicating the physiological relevance of the V-ATPase-mediated surfactant secretion. Finally, silencing of V-ATPase a1 and B2 subunits decreased stimulated surfactant secretion, indicating that these subunits were crucial for surfactant secretion. We conclude that V-ATPase regulates surfactant secretion via an increased Ca(2+ mobilization from lamellar bodies and endoplasmic reticulum, and the activation of PKC and CaMKII. Our finding revealed a previously unrealized role of V-ATPase in surfactant secretion.

  12. Interaction of nonionic surfactant AEO9 with ionic surfactants

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhi-guo; YIN Hong


    The interaction in two mixtures of a nonionic surfactant AEO9 (C12H25O(CH2CH2O)9H) and different ionic surfactants was investigated. The two mixtures were AEO9/sodium dodecyl sulfate (SDS) and AEO9/cetyltrimethylammonium bromide (CTAB) at molar fraction of AEO9, αAEO9 =0.5. The surface properties of the surfactants, critical micelle concentration (CMC),effectiveness of surface tension reduction (γCMC), maximum surface excess concentration (Гmax) and minimum area per molecule at the air/solution interface (Amin) were determined for both individual surfactants and their mixtures. The significant deviations from ideal behavior (attractive interactions) of the nonionic/ionic surfactant mixtures were determined. Mixtures of both AEO9/SDS and AEO9/CTAB exhibited synergism in surface tension reduction efficiency and mixed micelle formation, but neither exhibited synergism in surface tension reduction effectiveness.

  13. Airway management and morbid obesity

    DEFF Research Database (Denmark)

    Kristensen, Michael S


    Morbidly obese patients present with excess fatty tissue externally on the breast, neck, thoracic wall and abdomen and internally in the mouth, pharynx and abdomen. This excess tissue tends to make access (intubation, tracheostomy) to and patency (during sedation or mask ventilation) of the upper...... in morbidly obese patients and should be followed by actions to counteract atelectasis formation. The decision as to weather to use a rapid sequence induction, an awake intubation or a standard induction with hypnotics should depend on the thorough airway examination and comorbidity and should not be based...... solely on whether morbid obesity is present or not. It is important to ensure sufficient depth of anaesthesia before initiating manipulation of the airway because inadequate anaesthesia depth predisposes to aspiration if airway management becomes difficult. The intubating laryngeal mask airway is more...

  14. 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


    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

  15. Theoretical model to investigate the alkyl chain and anion dependent interactions of gemini surfactant with bovine serum albumin. (United States)

    Vishvakarma, Vijay K; Kumari, Kamlesh; Patel, Rajan; Dixit, V S; Singh, Prashant; Mehrotra, Gopal K; Chandra, Ramesh; Chakrawarty, Anand Kumar


    Surfactants are used to prevent the irreversible aggregation of partially refolded proteins and they also assist in protein refolding. We have reported the design and screening of gemini surfactant to stabilize bovine serum albumin (BSA) with the help of computational tool (iGEMDOCK). A series of gemini surfactant has been designed based on bis-N-alkyl nicotinate dianion via varying the alkyl group and anion. On changing the alkyl group and anion of the surfactant, the value of Log P changes means polarity of surfactant can be tuned. Further, the virtual screening of the gemini surfactant has been carried out based on generic evolutionary method. Herein, thermodynamic data was studied to determine the potential of gemini surfactant as BSA stabilizer. Computational tools help to find out the efficient gemini surfactant to stabilize the BSA rather than to use the surfactant randomly and directionless for the stabilization. It can be confirmed through the experimental techniques. Previously, researcher synthesized one of the designed and used gemini surfactant to stabilize the BSA and their interactions were confirmed through various techniques and computational docking. But herein, the authors find the most competent gemini surfactant to stabilize BSA using computational tools on the basis of energy score. Different from the single chain surfactant, the gemini surfactants exhibit much stronger electrostatic and hydrophobic interactions with the protein and are thus effective at much lower concentrations. Based on the present study, it is expected that gemini surfactants may prove useful in the protein stabilization operations and may thus be effectively employed to circumvent the problem of misfolding and aggregation.

  16. Self-Assembling Peptide Surfactants A6K and A6D Adopt a-Helical Structures Useful for Membrane Protein Stabilization

    Directory of Open Access Journals (Sweden)

    Furen Zhuang


    Full Text Available Elucidation of membrane protein structures have been greatly hampered by difficulties in producing adequately large quantities of the functional protein and stabilizing them. A6D and A6K are promising solutions to the problem and have recently been used for the rapid production of membrane-bound G protein-coupled receptors (GPCRs. We propose that despite their short lengths, these peptides can adopt α-helical structures through interactions with micelles formed by the peptides themselves. These α-helices are then able to stabilize α-helical motifs which many membrane proteins contain. We also show that A6D and A6K can form β-sheets and appear as weak hydrogels at sufficiently high concentrations. Furthermore, A6D and A6K together in sodium dodecyl sulfate (SDS can form expected β-sheet structures via a surprising α-helical intermediate.

  17. Surfactant monitoring by foam generation (United States)

    Mullen, Ken I.


    A device for monitoring the presence or absence of active surfactant or other surface active agents in a solution or flowing stream based on the formation of foam or bubbles is presented. The device detects the formation of foam with a light beam or conductivity measurement. The height or density of the foam can be correlated to the concentration of the active surfactant present.

  18. Surfactant adsorption kinetics in microfluidics (United States)

    Riechers, Birte; Maes, Florine; Akoury, Elias; Semin, Benoît; Gruner, Philipp; Baret, Jean-Christophe


    Emulsions are metastable dispersions. Their lifetimes are directly related to the dynamics of surfactants. We design a microfluidic method to measure the kinetics of adsorption of surfactants to the droplet interface, a key process involved in foaming, emulsification, and droplet coarsening. The method is based on the pH decay in the droplet as a direct measurement of the adsorption of a carboxylic acid surfactant to the interface. From the kinetic measurement of the bulk equilibration of the pH, we fully determine the adsorption process of the surfactant. The small droplet size and the convection during the droplet flow ensure that the transport of surfactant through the bulk is not limiting the kinetics of adsorption. To validate our measurements, we show that the adsorption process determines the timescale required to stabilize droplets against coalescence, and we show that the interface should be covered at more than 90% to prevent coalescence. We therefore quantitatively link the process of adsorption/desorption, the stabilization of emulsions, and the kinetics of solute partitioning—here through ion exchange—unraveling the timescales governing these processes. Our method can be further generalized to other surfactants, including nonionic surfactants, by making use of fluorophore-surfactant interactions.


    Surfactants used to enhance remediation of soils by soil washing are often lost in the process. Neither the amount nor the cause of this loss is known. It is assumed that clays present in the soil are responsible for the loss of the surfactant. In this papere, adsorption prope...

  20. beta-Catenin regulates airway smooth muscle contraction

    NARCIS (Netherlands)

    Jansen, Sepp R.; Van Ziel, Anna M.; Baarsma, Hoeke A.; Gosens, Reinoud


    Jansen SR, Van Ziel AM, Baarsma HA, Gosens R. beta-Catenin regulates airway smooth muscle contraction. Am J Physiol Lung Cell Mol Physiol 299: L204-L214, 2010. First published May 14, 2010; doi:10.1152/ajplung.00020.2010.-beta-Catenin is an 88-kDa member of the armadillo family of proteins that is a

  1. Overexpression of mclca3 in airway epithelium of asthmatic murine models with airway inflammation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hui-lan; HE Li


    Asthma is a worldwide prevalent disease that is a considerable health burden in many countries.1 In recent years, the airway epithelium is increasingly recognized as a central contributor to the pathogenesis of asthma.2 One of the most highly induced genes in epithelial cells in experimental allergic airway disease is the third murine calcium-activated chloride channel homologue (mclca3, alias gob-5). Its human homology protein is hCLCA1,3,4 which has been identified as clinically relevant molecules in diseases with secretory dysfunctions including asthma and cystic fibrosis. In initial studies, mclca3 was thought to be a member of calcium-activated chloride channel (CaCCs) family,whereas some new interesting reports suggest that the two mclca3 cleavage products cannot form an anion channel on their own but may instead act as extracellular signaling molecules with as yet unknown functions and interacting partners.5

  2. A new removable airway stent

    Directory of Open Access Journals (Sweden)

    Tore Amundsen


    Full Text Available Background: Malignant airway obstruction is a feared complication and will most probably occur more frequently in the future because of increasing cancer incidence and increased life expectancy in cancer patients. Minimal invasive treatment using airway stents represents a meaningful and life-saving palliation. We present a new removable airway stent for improved individualised treatment. Methods: To our knowledge, the new airway stent is the world's first knitted and uncovered self-expanding metal stent, which can unravel and be completely removed. In an in vivo model using two anaesthetised and spontaneously breathing pigs, we deployed and subsequently removed the stents by unravelling the device. The procedures were executed by flexible bronchoscopy in an acute and a chronic setting – a ‘proof-of-principle’ study. Results: The new stent was easily and accurately deployed in the central airways, and it remained fixed in its original position. It was easy to unravel and completely remove from the airways without clinically significant complications. During the presence of the stent in the chronic study, granulation tissue was induced. This tissue disappeared spontaneously with the removal. Conclusions: The new removable stent functioned according to its purpose and unravelled easily, and it was completely removed without significant technical or medical complications. Induced granulation tissue disappeared spontaneously. Further studies on animals and humans are needed to define its optimal indications and future use.

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

    DEFF Research Database (Denmark)

    Ortiz, Elisa Parra; Perez-Gil, Jesús


    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......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...

  4. Biophysicochemical Interaction of a Clinical Pulmonary Surfactant with Nanoalumina. (United States)

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


    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.

  5. Large scale molecular dynamics study of polymer-surfactant complex (United States)

    Goswami, Monojoy; Sumpter, Bobby


    In this work, we study the self-assembly of cationic polyelectrolytes mediated by anionic surfactants in dilute or semi-dilute and gel states. The understanding of the dilute system is a requirement for the understanding of gel states. The importance of polyelectrolyte with oppositely charged colloidal particles can be found in biological systems, such as immobilization of enzymes in polyelectrolyte complexes or nonspecific association of DNA with protein. With the same understanding, interaction of surfactants with polyelectrolytes shows intriguing phenomena that are important for both in academic research as well as industrial applications. Many useful properties of PE surfactant complexes come from the highly ordered structures of surfactant self-assembly inside the PE aggregate. We do large scale molecular dynamics simulation using LAMMPS to understand the structure and dynamics of PE-surfactant systems. Our investigation shows highly ordered ring-string structures that have been observed experimentally in biological systems. We will investigate many different properties of PE-surfactant complexation which will be helpful for pharmaceutical, engineering and biological applications.

  6. Composition, structure and mechanical properties define performance of pulmonary surfactant membranes and films. (United States)

    Parra, Elisa; Pérez-Gil, Jesús


    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.

  7. Surface characterization and AFM imaging of mixed fibrinogen-surfactant films. (United States)

    Hassan, Natalia; Maldonado-Valderrama, Julia; Gunning, A Patrick; Morris, Victor J; Ruso, Juan M


    This study describes the adsorption behavior of mixed protein/surfactant systems at the air-water interface: specifically fibrinogen and the fluorinated and hydrogenated surfactants (C(8)FONa, C(8)HONa, and C(12)HONa). Surface tension techniques and atomic force microscopy (AFM) have been combined to investigate the adsorption behavior of these mixed systems. Interfacial rheology showed that fibrinogen has a low dilatational modulus at the air-water interface when compared to other proteins, suggesting the formation of a weak surface network. Fluorinated and hydrogenated surfactants severely decreased the dilatational modulus of the adsorbed fibrinogen film at the air-water interface. These measurements suggest the progressive displacement of fibrinogen from the air-water interface by both types of surfactants. However, in the case of fibrinogen/fluorinated surfactant systems, surface tension and dilatational rheology measurements suggest the formation of complexes with improved surface activity. AFM imaging of fibrinogen in the presence and absence of surfactants provided new information on the structure of mixed surface films, and revealed new features of the interaction of fibrinogen with hydrogenated and fluorinated surfactants. These studies suggest complexes formed between fibrinogen and fluorinated surfactants which are more surface active than fibrinogen, while the absence of interaction between fibrinogen and hydrogenated surfactants (C(8)HONa and C(12)HONa) results in compaction of the surface layer.

  8. Vessel-guided airway tree segmentation

    DEFF Research Database (Denmark)

    Lo, Pechin Chien Pau; Sporring, Jon; Ashraf, Haseem


    This paper presents a method for airway tree segmentation that uses a combination of a trained airway appearance model, vessel and airway orientation information, and region growing. We propose a voxel classification approach for the appearance model, which uses a classifier that is trained...... to differentiate between airway and non-airway voxels. This is in contrast to previous works that use either intensity alone or hand crafted models of airway appearance. We show that the appearance model can be trained with a set of easily acquired, incomplete, airway tree segmentations. A vessel orientation...... similarity measure is introduced, which indicates how similar the orientation of an airway candidate is to the orientation of the neighboring vessel. We use this vessel orientation similarity measure to overcome regions in the airway tree that have a low response from the appearance model. The proposed...

  9. Analysis of airways in computed tomography

    DEFF Research Database (Denmark)

    Petersen, Jens

    Chronic Obstructive Pulmonary Disease (COPD) is major cause of death and disability world-wide. It affects lung function through destruction of lung tissue known as emphysema and inflammation of airways, leading to thickened airway walls and narrowed airway lumen. Computed Tomography (CT) imaging...... have become the standard with which to assess emphysema extent but airway abnormalities have so far been more challenging to quantify. Automated methods for analysis are indispensable as the visible airway tree in a CT scan can include several hundreds of individual branches. However, automation...... of scan on airway dimensions in subjects with and without COPD. The results show measured airway dimensions to be affected by differences in the level of inspiration and this dependency is again influenced by COPD. Inspiration level should therefore be accounted for when measuring airways, and airway...

  10. 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 (United States)

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


    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

  11. Innovation in surfactant therapy II: surfactant administration by aerosolization. (United States)

    Pillow, J Jane; Minocchieri, S


    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.

  12. Comparative characterization of pulmonary surfactant aggregates and alkaline phosphatase isozymes in human lung carcinoma tissue. (United States)

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


    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.

  13. A review on airway biomarkers: exposure, effect and susceptibility. (United States)

    Corradi, Massimo; Goldoni, Matteo; Mutti, Antonio


    Current research in pulmonology requires the use of biomarkers to investigate airway exposure and diseases, for both diagnostic and prognostic purposes. The traditional approach based on invasive approaches (lung lavages and biopsies) can now be replaced, at least in part, through the use of non invasively collected specimens (sputum and breath), in which biomarkers of exposure, effect and susceptibility can be searched. The discovery of specific lung-related proteins, which can spill over in blood or excreted in urine, further enhanced the spectrum of airway specific biomarkers to be studied. The recent introduction of high-performance 'omic' technologies - genomics, proteomics and metabolomics, and the rate at which biomarker candidates are being discovered, will permit the use of a combination of biomarkers for a more precise selection of patient with different outcomes and responses to therapies. The aim of this review is to critically evaluate the use of airway biomarkers in the context of research and clinical practice.

  14. Upper airway resistance syndrome. (United States)

    Montserrat, J M; Badia, J R


    This article reviews the clinical picture, diagnosis and management of the upper airway resistance syndrome (UARS). Presently, there is not enough data on key points like the frequency of UARS and the morbidity associated with this condition. Furthermore, the existence of LIARS as an independent sleep disorder and its relation with snoring and obstructive events is in debate. The diagnosis of UARS is still a controversial issue. The technical limitations of the classic approach to monitor airflow with thermistors and inductance plethysmography, as well as the lack of a precise definition of hypopnea, may have led to a misinterpretation of UARS as an independent diagnosis from the sleep apnea/hypopnea syndrome. The diagnosis of this syndrome can be missed using a conventional polysomnographic setting unless appropriate techniques are applied. The use of an esophageal balloon to monitor inspiratory effort is currently the gold standard. However, other sensitive methods such as the use of a pneumotachograph and, more recently, nasal cannula/pressure transducer systems or on-line monitoring of respiratory impedance with the forced oscillation technique may provide other interesting possibilities. Recognition and characterization of this subgroup of patients within sleep breathing disorders is important because they are symptomatic and may benefit from treatment. Management options to treat UARS comprise all those currently available for sleep apnea/hypopnea syndrome (SAHS). However, the subset of patients classically identified as LIARS that exhibit skeletal craneo-facial abnormalities might possibly obtain further benefit from maxillofacial surgery.

  15. Interaction of nonionic surfactant AEO9 with ionic surfactants*



    The interaction in two mixtures of a nonionic surfactant AEO9 (C12H25O(CH2CH2O)9H) and different ionic surfactants was investigated. The two mixtures were AEO9/sodium dodecyl sulfate (SDS) and AEO9/cetyltrimethylammonium bromide (CTAB) at molar fraction of AEO9, α AEO9=0.5. The surface properties of the surfactants, critical micelle concentration (CMC), effectiveness of surface tension reduction (γ CMC), maximum surface excess concentration (Γ max) and minimum area per...


    Directory of Open Access Journals (Sweden)

    T. P. Pirog


    Full Text Available It was shown literature and own experimental data concerning the use of microbial surface active glycolipids (rhamno-, sophoro- and trehalose lipids and lipopeptides for water and soil purification from oil and other hydrocarbons, removing toxic heavy metals (Cu2+, Cd2+, Ni2+, Pb2+, degradation of complex pollution (oil and other hydrocarbons with heavy metals, and the role of microbial surfactants in phytoremediation processes. The factors that limit the use of microbial surfactants in environmental technologies are discussed. Thus, at certain concentrations biosurfactant can exhibit antimicrobial properties and inhibit microorganisms destructing xenobiotics. Microbial biodegradability of surfactants may also reduce the effectiveness of bioremediation. Development of effective technologies using microbial surfactants should include the following steps: monitoring of contaminated sites to determine the nature of pollution and analysis of the autochthonous microbiota; determining the mode of surfactant introduction (exogenous addition of stimulation of surfactant synthesis by autochthonous microbiota; establishing an optimal concentration of surfactant to prevent exhibition of antimicrobial properties and rapid biodegradation; research both in laboratory and field conditions.

  17. Surfactant enhanced volumetric sweep efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Harwell, J.H.; Scamehorn, J.F.


    Surfactant-enhanced waterflooding is a novel EOR method aimed to improve the volumetric sweep efficiencies in reservoirs. The technique depends upon the ability to induce phase changes in surfactant solutions by mixing with surfactants of opposite charge or with salts of appropriate type. One surfactant or salt solution is injected into the reservoir. It is followed later by injection of another surfactant or salt solution. The sequence of injections is arranged so that the two solutions do not mix until they are into the permeable regions well away from the well bore. When they mix at this point, by design they form a precipitate or gel-like coacervate phase, plugging this permeable region, forcing flow through less permeable regions of the reservoir, improving sweep efficiency. The selectivity of the plugging process is demonstrated by achieving permeability reductions in the high permeable regions of Berea sandstone cores. Strategies were set to obtain a better control over the plug placement and the stability of plugs. A numerical simulator has been developed to investigate the potential increases in oil production of model systems. Furthermore, the hardness tolerance of anionic surfactant solutions is shown to be enhanced by addition of monovalent electrolyte or nonionic surfactants. 34 refs., 32 figs., 8 tabs.

  18. 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. (United States)

    Puthusseri, Bijesh; Marudamuthu, Amarnath S; Tiwari, Nivedita; Fu, Jian; Idell, Steven; Shetty, Sreerama


    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.

  19. Lipoteichoic acid induces surfactant protein-A biosynthesis in human alveolar type II epithelial cells through activating the MEK1/2-ERK1/2-NF-κB pathway

    Directory of Open Access Journals (Sweden)

    Liu Feng-Lin


    Full Text Available Abstract Background Lipoteichoic acid (LTA, a gram-positive bacterial outer membrane component, can cause septic shock. Our previous studies showed that the gram-negative endotoxin, lipopolysaccharide (LPS, could induce surfactant protein-A (SP-A production in human alveolar epithelial (A549 cells. Objectives In this study, we further evaluated the effect of LTA on SP-A biosynthesis and its possible signal-transducing mechanisms. Methods A549 cells were exposed to LTA. Levels of SP-A, nuclear factor (NF-κB, extracellular signal-regulated kinase 1/2 (ERK1/2, and mitogen-activated/extracellular signal-regulated kinase kinase (MEK1 were determined. Results Exposure of A549 cells to 10, 30, and 50 μg/ml LTA for 24 h did not affect cell viability. Meanwhile, when exposed to 30 μg/ml LTA for 1, 6, and 24 h, the biosynthesis of SP-A mRNA and protein in A549 cells significantly increased. As to the mechanism, LTA enhanced cytosolic and nuclear NF-κB levels in time-dependent manners. Pretreatment with BAY 11–7082, an inhibitor of NF-κB activation, significantly inhibited LTA-induced SP-A mRNA expression. Sequentially, LTA time-dependently augmented phosphorylation of ERK1/2. In addition, levels of phosphorylated MEK1 were augmented following treatment with LTA. Conclusions Therefore, this study showed that LTA can increase SP-A synthesis in human alveolar type II epithelial cells through sequentially activating the MEK1-ERK1/2-NF-κB-dependent pathway.

  20. 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. (United States)

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


    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

  1. Electrokinetic investigation of surfactant adsorption. (United States)

    Bellmann, C; Synytska, A; Caspari, A; Drechsler, A; Grundke, K


    Fuerstenau [D.W. Fuerstenau, in: M.L. Hair (Ed.), Dekker, New York, 1971, p. 143] has already discussed the role of hydrocarbon chain of surfactants, the effect of alkyl chain length, chain structure and the pH of the solution on the adsorption process of surfactants. Later Kosmulski [M. Kosmulski, Chemical Properties of Material Surfaces, Surfactant Science Series, vol. 102, Dekker, New York, Basel, 2001] included the effect of surfactant concentration, equilibration time, temperature and electrolyte in his approaches. Certainly, the character of the head groups of the surfactant and the properties of the adsorbent surface are the basis for the adsorption process. Different surfactants and adsorbents cause different adsorption mechanisms described firstly by Rosen [M.J. Rosen, Surfactants and Interfacial Phenomena, second ed., Wiley, New York, 1989]. These adsorption mechanisms and their influencing factors were studied by electrokinetic investigations. Here only changes of the charges at the surfaces could be detected. To control the results of electrokinetic investigations they were compared with results from ellipsometric measurements. In the case of surfactant adsorption the chain length was vitally important. It could be shown by the adsorption of alkyl trimethyl ammonium bromides onto polymer films spin coated at wafer surfaces. The influence of the chain length depending on surface properties of the polymer film was studied. Streaming potential measurements were applied for these investigations. The obtained results enabled us to calculate the molar cohesive free energy per mol of CH2-group in the alkaline chain of the surfactant if all other specific adsorption effects were neglected.

  2. Chlorinated pool attendance, airway epithelium defects and the risks of allergic diseases in adolescents: Interrelationships revealed by circulating biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Bernard, Alfred, E-mail:; Nickmilder, Marc; Dumont, Xavier


    It has been suggested that allergic diseases might be epithelial disorders driven by various environmental stressors but the epidemiological evidence supporting this concept is limited. In a cross-sectional study of 835 school adolescents (365 boys; mean age, 15.5 yr), we measured the serum concentrations of Club cell protein (CC16), surfactant-associated protein D (SP-D) and of total and aeroallergen-specific IgE. We used the serum CC16/SP-D concentration ratio as an index integrating changes in the permeability (SP-D) and secretory function (CC16) of the airway epithelium. In both sexes, early swimming in chlorinated pools emerged as the most consistent and strongest predictor of low CC16 and CC16/SP-D ratio in serum. Among girls, a low CC16/SP-D ratio was associated with increased odds (lowest vs. highest tertile) for pet sensitization (OR 2.97, 95% CI 1.19–8.22) and for hay fever in subjects sensitized to pollen (OR 4.12, 95% CI 1.28–14.4). Among boys, a low CC16/SP-D ratio was associated with increased odds for house-dust mite (HDM) sensitization (OR 2.01, 95% CI 1.11–3.73), for allergic rhinitis in subjects sensitized to HDM (OR 3.52, 95% CI 1.22–11.1) and for asthma in subjects sensitized to any aeroallergen (OR 3.38, 95% CI 1.17–11.0), HDM (OR 5.20, 95% CI 1.40–24.2) or pollen (OR 5.82, 95% CI 1.51–27.4). Odds for allergic sensitization or rhinitis also increased with increasing SP-D or decreasing CC16 in serum. Our findings support the hypothesis linking the development of allergic diseases to epithelial barrier defects due to host factors or environmental stressors such as early swimming in chlorinated pools. - Highlights: • We conducted a cross-sectional study of 835 school adolescents. • The airway epithelium integrity was evaluated by measuring serum pneumoproteins. • The risk of allergic diseases was associated with a defective airway epithelium. • Childhood swimming in chlorinated pools can cause persistent epithelial

  3. Prevention of house dust mite induced allergic airways disease in mice through immune tolerance. (United States)

    Agua-Doce, Ana; Graca, Luis


    Allergic airways disease is a consequence of a Th2 response to an allergen leading to a series of manifestations such as production of allergen-specific IgE, inflammatory infiltrates in the airways, and airway hyper-reactivity (AHR). Several strategies have been reported for tolerance induction to allergens leading to protection from allergic airways disease. We now show that CD4 blockade at the time of house dust mite sensitization induces antigen-specific tolerance in mice. Tolerance induction is robust enough to be effective in pre-sensitized animals, even in those where AHR was pre-established. Tolerant mice are protected from airways eosinophilia, Th2 lung infiltration, and AHR. Furthermore, anti-CD4 treated mice remain immune competent to mount immune responses, including Th2, to unrelated antigens. Our findings, therefore, describe a strategy for tolerance induction potentially applicable to other immunogenic proteins besides allergens.

  4. Interfacial behavior of pulmonary surfactant preparations containing egg yolk lecithin. (United States)

    Nakahara, Hiromichi; Shibata, Osamu


    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.

  5. Interaction of bovine serum albumin with N-acyl amino acid based anionic surfactants: Effect of head-group hydrophobicity. (United States)

    Ghosh, Subhajit; Dey, Joykrishna


    The function of a protein depends upon its structure and surfactant molecules are known to alter protein structure. For this reason protein-surfactant interaction is important in biological, pharmaceutical, and cosmetic industries. In the present work, interactions of a series of anionic surfactants having the same hydrocarbon chain length, but different amino acid head group, such as l-alanine, l-valine, l-leucine, and l-phenylalanine with the transport protein, bovine serum albumin (BSA), were studied at low surfactant concentrations using fluorescence and circular dichroism (CD) spectroscopy, and isothermal titration calorimetry (ITC). The results of fluorescence measurements suggest that the surfactant molecules bind simultaneously to the drug binding site I and II of the protein subdomain IIA and IIIA, respectively. The fluorescence as well as CD spectra suggest that the conformation of BSA goes to a more structured state upon surfactant binding at low concentrations. The binding constants of the surfactants were determined by the use of fluorescence as well as ITC measurements and were compared with that of the corresponding glycine-derived surfactant. The binding constant values clearly indicate a significant head-group effect on the BSA-surfactant interaction and the interaction is mainly hydrophobic in nature.

  6. Anaerobic Biodegradation of Detergent Surfactants

    Directory of Open Access Journals (Sweden)

    Erich Jelen


    Full Text Available Detergent surfactantscan be found in wastewater in relevant concentrations. Most of them are known as ready degradable under aerobic conditions, as required by European legislation. Far fewer surfactants have been tested so far for biodegradability under anaerobic conditions. The natural environment is predominantly aerobic, but there are some environmental compartments such as river sediments, sub-surface soil layer and anaerobic sludge digesters of wastewater treatment plants which have strictly anaerobic conditions. This review gives an overview on anaerobic biodegradation processes, the methods for testing anaerobic biodegradability, and the anaerobic biodegradability of different detergent surfactant types (anionic, nonionic, cationic, amphoteric surfactants.

  7. MicroRNA-206 regulates surfactant secretion by targeting VAMP-2. (United States)

    Zhang, Honghao; Guo, Yujie; Mishra, Amarjit; Gou, Deming; Chintagari, Narendranath Reddy; Liu, Lin


    Lung surfactant secretion is a highly regulated process. Our previous studies have shown that VAMP-2 is essential for surfactant secretion. In the present study we investigated the role of miR-206 in surfactant secretion through VAMP-2. VAMP-2 was confirmed to be a target of miR-206 by 3'-untranslational region (3'-UTR) luciferase assay. Mutations in the predicated miR-206 binding sites reduced the binding of miR-206 to the 3'-UTR of VAMP-2. miR-206 decreased the expression of VAMP-2 protein and decreased the lung surfactant secretion in alveolar type II cells. In conclusion, miR-206 regulates lung surfactant secretion by limiting the availability of VAMP-2 protein.

  8. Airway branching morphogenesis in three dimensional culture

    Directory of Open Access Journals (Sweden)

    Gudjonsson Thorarinn


    Full Text Available Abstract Background Lungs develop from the fetal digestive tract where epithelium invades the vascular rich stroma in a process called branching morphogenesis. In organogenesis, endothelial cells have been shown to be important for morphogenesis and the maintenance of organ structure. The aim of this study was to recapitulate human lung morphogenesis in vitro by establishing a three dimensional (3D co-culture model where lung epithelial cells were cultured in endothelial-rich stroma. Methods We used a human bronchial epithelial cell line (VA10 recently developed in our laboratory. This cell line cell line maintains a predominant basal cell phenotype, expressing p63 and other basal markers such as cytokeratin-5 and -14. Here, we cultured VA10 with human umbilical vein endothelial cells (HUVECs, to mimic the close interaction between these cell types during lung development. Morphogenesis and differentiation was monitored by phase contrast microscopy, immunostainings and confocal imaging. Results We found that in co-culture with endothelial cells, the VA10 cells generated bronchioalveolar like structures, suggesting that lung epithelial branching is facilitated by the presence of endothelial cells. The VA10 derived epithelial structures display various complex patterns of branching and show partial alveolar type-II differentiation with pro-Surfactant-C expression. The epithelial origin of the branching VA10 colonies was confirmed by immunostaining. These bronchioalveolar-like structures were polarized with respect to integrin expression at the cell-matrix interface. The endothelial-induced branching was mediated by soluble factors. Furthermore, fibroblast growth factor receptor-2 (FGFR-2 and sprouty-2 were expressed at the growing tips of the branching structures and the branching was inhibited by the FGFR-small molecule inhibitor SU5402. Discussion In this study we show that a human lung epithelial cell line can be induced by endothelial cells to

  9. Treating asthma means treating airway smooth muscle cells

    NARCIS (Netherlands)

    Zuyderduyn, S; Sukkar, M B; Fust, A; Dhaliwal, S; Burgess, J K


    Asthma is characterised by airway hyperresponsiveness, airway inflammation and airway remodelling. Airway smooth muscle cells are known to be the main effector cells of airway narrowing. In the present paper, studies will be discussed that have led to a novel view of the role of airway smooth muscle

  10. Treatment with exogenous surfactant stimulates endogenous surfactant synthesis in premature infants with respiratory distress syndrome

    NARCIS (Netherlands)

    Bunt, JEH; Carnielli, VP; Janssen, DJ; Wattimena, JLD; Hop, WC; Sauer, PJ; Zimmermann, LJI


    Objective: Treatment of preterm infants with respiratory distress syndrome (RDS) with exogenous surfactant has greatly improved clinical outcome. Some infants require multiple doses, and it has not been studied whether these large amounts of exogenous surfactant disturb endogenous surfactant metabol

  11. Electrochemical Oscillations Induced by Surfactants

    Institute of Scientific and Technical Information of China (English)

    翟俊红; 贺占博


    A new type of electrochemical oscillation induced by surfactant was observed in experiments. The electrochemical system is a Daniell cell with a copper rod in CuSO4 aqueous and an aluminum rod in Al(NO3)3 aqueous as electrodes. The surfactants are CTAB, TX-100, SLS. The addition of trace surfactant solution by a micro-syringe made the original monotonously changing electrochemical system produce obvious periodic phenomena. At the mean time, the copper ion selective electrode and Hg2SO4 reference electrode were used to monitor the copper electrode reaction and determine its rate constant k of first order reaction. According to the experimental results of electrode reaction kinetics, the possible mechanism was found to be the polarization induced from the directional adsorption of trace surfactant on the electrode surface. That is the electrochemical oscillations.

  12. Multiscale Vessel-guided Airway Tree Segmentation

    DEFF Research Database (Denmark)

    Lo, Pechin Chien Pau; Sporring, Jon; de Bruijne, Marleen


    that is trained to differentiate between airway and non-airway voxels. Vessel and airway orientation information are used in the form of a vessel orientation similarity measure, which indicates how similar the orientation of the an airway candidate is to the orientation of the neighboring vessel. The method...... is evaluated within EXACT’09 on a diverse set of CT scans. Results show a favorable combination of a relatively large portion of the tree detected correctly with very few false positives....

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



    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...

  14. Up-Regulation of Endothelin Receptors Induced by Cigarette Smoke — Involvement of MAPK in Vascular and Airway Hyper-Reactivity

    Directory of Open Access Journals (Sweden)

    Yaping Zhang


    Full Text Available Cigarette smoke exposure is well known to cause cardiovascular and airway diseases, both of which are leading causes of death and disability in the world. However, the molecular mechanisms that link cigarette smoke to cardiovascular and airway diseases are not fully understood. Vascular and airway hyper-reactivity plays an important role in the pathogenesis of cardiovascular and airway diseases. Recent studies have demonstrated that endothelin receptor up-regulation mediates vascular and airway hyper-reactivity in response to endothelin-1 (ET-1, endothelin receptor agonist in cardiovascular and airway diseases. In the vasculature and airways, the main functional consequences of up-regulated endothelin receptors by cigarette smoke exposure are enhanced contraction and proliferation of the smooth muscle cells, which subsequently result in abnormal contraction (spasm and adverse proliferation (remodeling of the vasculature and airways. The structural alteration by adverse remodeling involves changes in cell growth, cell death, cell migration, and production or degradation of the extracellular matrix. This review focuses on cigarette smoke exposure that induces activation of intracellular mitogen-activated protein kinase (MAPK and subsequently results in the up-regulation of endothelin receptors in the vasculature and airways, which mediates vascular and airway hyper-reactivity, one of the important pathogenic characteristics of cardiovascular and airway diseases. Understanding the molecular mechanisms of how cigarette smoke causes up-regulation of endothelin receptors in the vasculature and airways may provide new strategies for the treatment of cigarette smoke—associated cardiovascular and lung diseases.

  15. 被动吸烟对大鼠血清肺表面活性蛋白A、D表达的影响%Effect of passive smoking on the expression of surfactant protein A and D in rats

    Institute of Scientific and Technical Information of China (English)

    韩书芝; 梁会朋; 张凤蕊; 平芬


    Objective Establishment of rat model of passive smoking by smoking,to observe the effect of passive smoking on surfactant protein A and D in rats,to explore the mechanism of immune injury in lung injury by passive smoking.Methods Fifty male wistar rats were randomly divided into five groups:normal control group,passive smoking 4-week group,passive smoking 8-week group,passive smoking 12-week group and cessive smoking group.Observed the pathomorphism changes of lung tissue by Hematoxylinand eosin staining (HE) staining.Detected the the levels of surfactant protein A and D (SP-A、SP-D) in the serum.Results passive smoking can lead to the response of lung inflammatory.The levels of SP-A、D in the serum of rats in passive smoking groups were significantly higher than those in normal control group.Conclusions The expression of SP-A、D significantly increased in the serum of rats with passive smoking.SP-A、D may be implicated in the pathogenesis of lung injury caused by passive smoking.%目的 通过烟熏法建立大鼠被动吸烟模型,观察被动吸烟和戒烟对血清肺表面活性蛋白A、D的影响,探讨被动吸烟肺损伤的发生机制.方法 选择健康雄性Wistar大鼠50只,随机分为5组,分别为正常对照组、被动吸烟4周组、被动吸烟8周组、被动吸烟12周组和戒烟组.HE染色观察肺组织的病理改变,采用酶联免疫吸附测定(ELISA)方法检测血清肺表面活性蛋白A、D含量.结果 被动吸烟可导致肺组织炎症反应和肺气肿改变;被动吸烟组和戒烟组大鼠血清肺表面活性蛋白A、D含量较正常对照组升高,随着被动吸烟时间的延长,血清肺表面活性蛋白A、D含量逐渐增加;戒烟组较被动吸烟12周组血清肺表面活性蛋白A、D含量降低.结论 被动吸烟可引起血清肺表面活性蛋白A、D表达增加,提示血清肺表面活性蛋白A、D可能参与了被动吸烟导致肺损伤的发病过程.

  16. Functional phenotype of airway myocytes from asthmatic airways

    NARCIS (Netherlands)

    Wright, David B.; Trian, Thomas; Siddiqui, Sana; Pascoe, Chris D.; Ojo, Oluwaseun O.; Johnson, Jill R.; Dekkers, Bart G. J.; Dakshinamurti, Shyamala; Bagchi, Rushita; Burgess, Janette K.; Kanabar, Varsha


    In asthma, the airway smooth muscle (ASM) cell plays a central role in disease pathogenesis through cellular changes which may impact on its microenvironment and alter ASM response and function. The answer to the long debated question of what makes a 'healthy' ASM cell become 'asthmatic' still remai

  17. 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)


    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

  18. Airway epithelial NF-κB activation promotes Mycoplasma pneumoniae clearance in mice.

    Directory of Open Access Journals (Sweden)

    Di Jiang

    Full Text Available Respiratory infections including atypical bacteria Mycoplasma pneumoniae (Mp contribute to the pathobiology of asthma and chronic obstructive pulmonary disease (COPD. Mp infection mainly targets airway epithelium and activates various signaling pathways such as nuclear factor κB (NF-κB. We have shown that short palate, lung, and nasal epithelium clone 1 (SPLUNC1 serves as a novel host defense protein and is up-regulated upon Mp infection through NF-κB activation in cultured human and mouse primary airway epithelial cells. However, the in vivo role of airway epithelial NF-κB activation in host defense against Mp infection has not been investigated. In the current study, we investigated the effects of in vivo airway epithelial NF-κB activation on lung Mp clearance and its association with airway epithelial SPLUNC1 expression.Non-antimicrobial tetracycline analog 9-t-butyl doxycycline (9-TB was initially optimized in mouse primary tracheal epithelial cell culture, and then utilized to induce in vivo airway epithelial specific NF-κB activation in conditional NF-κB transgenic mice (CC10-(CAIKKβ with or without Mp infection. Lung Mp load and inflammation were evaluated, and airway epithelial SPLUNC1 protein was examined by immunohistochemistry. We found that 9-TB treatment in NF-κB transgene positive (Tg+, but not transgene negative (Tg- mice significantly reduced lung Mp load. Moreover, 9-TB increased airway epithelial SPLUNC1 protein expression in NF-κB Tg+ mice.By using the non-antimicrobial 9-TB, our study demonstrates that in vivo airway epithelial NF-κB activation promotes lung bacterial clearance, which is accompanied by increased epithelial SPLUNC1 expression.

  19. Mode of Glucocorticoid Actions in Airway Disease

    Directory of Open Access Journals (Sweden)

    Kazuhiro Ito


    Full Text Available Synthetic glucocorticoids are the most potent anti-inflammatory agents used to treat chronic inflammatory disease, such as asthma. However, a small number (<5% of asthmatic patients and almost all patients with chronic obstructive pulmonary disease (COPD do not respond well, or at all, to glucocorticoid therapy. If the molecular mechanism of glucocorticoid insensitivity is uncovered, it may in turn provide insight into the key mechanism of glucocorticoid action and allow a rational way to implement treatment regimens that restore glucocorticoid sensitivity. Glucocorticoids exert their effects by binding to a cytoplasmic glucocorticoid receptor (GR, which is subjected to post-translational modifications. Receptor phosphorylation, acetylation, nitrosylation, ubiquitinylation, and other modifications influence hormone binding, nuclear translocation, and protein half-life. Analysis of GR interactions to other molecules, such as coactivators or corepressors, may explain the genetic specificity of GR action. Priming with inflammatory cytokine or oxidative/nitrative stress is a mechanism for the glucocorticoid resistance observed in chronic inflammatory airway disease via reduction of corepressors or GR modification. Therapies targeting these aspects of the GR activation pathway may reverse glucocorticoid resistance in patients with glucocorticoid-insensitive airway disease and some patients with other inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease.

  20. Small angle neutron scattering studies on the interaction of cationic surfactants with bovine serum albumin

    Indian Academy of Sciences (India)

    Nuzhat Gull; S Chodankar; V K Aswal; Kabir-Ud-Din


    The structure of the protein–surfactant complex of bovine serum albumin (BSA) and cationic surfactants has been studied by small angle neutron scattering. At low concentrations, the CTAB monomers are observed to bind to the protein leading to an increase in its size. On the other hand at high concentrations, surfactant molecules aggregate along the unfolded polypeptide chain of the protein resulting in the formation of a fractal structure representing a necklace model of micelle-like clusters randomly distributed along the polypeptide chain. The fractal dimension as well as the size and number of micelles attached to the complex have been determined.

  1. Prolonged ozone exposure in an allergic airway disease model: Adaptation of airway responsiveness and airway remodeling

    Directory of Open Access Journals (Sweden)

    Park Chang-Soo


    Full Text Available Abstract Background Short-term exposure to high concentrations of ozone has been shown to increase airway hyper-responsiveness (AHR. Because the changes in AHR and airway inflammation and structure after chronic ozone exposure need to be determined, the goal of this study was to investigate these effects in a murine model of allergic airway disease. Methods We exposed BALB/c mice to 2 ppm ozone for 4, 8, and 12 weeks. We measured the enhanced pause (Penh to methacholine and performed cell differentials in bronchoalveolar lavage fluid. We quantified the levels of IL-4 and IFN-γ in the supernatants of the bronchoalveolar lavage fluids using enzyme immunoassays, and examined the airway architecture under light and electron microscopy. Results The groups exposed to ozone for 4, 8, and 12 weeks demonstrated decreased Penh at methacholine concentrations of 12.5, 25, and 50 mg/ml, with a dose-response curve to the right of that for the filtered-air group. Neutrophils and eosinophils increased in the group exposed to ozone for 4 weeks compared to those in the filtered-air group. The ratio of IL-4 to INF-γ increased significantly after exposure to ozone for 8 and 12 weeks compared to the ratio for the filtered-air group. The numbers of goblet cells, myofibroblasts, and smooth muscle cells showed time-dependent increases in lung tissue sections from the groups exposed to ozone for 4, 8, and 12 weeks. Conclusion These findings demonstrate that the increase in AHR associated with the allergic airway does not persist during chronic ozone exposure, indicating that airway remodeling and adaptation following repeated exposure to air pollutants can provide protection against AHR.

  2. Surfactant dysfunction in lung contusion with and without superimposed gastric aspiration in a rat model. (United States)

    Raghavendran, Krishnan; Davidson, Bruce A; Knight, Paul R; Wang, Zhengdong; Helinski, Jadwiga; Chess, Patricia R; Notter, Robert H


    This study investigates surfactant dysfunction in rats with lung contusion (LC) induced by blunt chest trauma. Rats at 24 h postcontusion had a decreased percent content of large surfactant aggregates in cell-free bronchoalveolar lavage (BAL) and altered large-aggregate composition with decreased phosphatidylcholine (PC), increased lyso-PC, and increased protein compared with uninjured controls. The surface activity of large aggregates on a pulsating bubble surfactometer was also severely impaired at 24 h postcontusion. Decreases in large surfactant aggregate content and surface activity were improved, but still apparent, at 48 and 72 h postcontusion compared with uninjured control rats and returned to normal by 96 h postcontusion. The functional importance of surfactant abnormalities in LC injury was documented in pilot studies showing that exogenous surfactant replacement at 24 h postcontusion improved inflation/deflation lung volumes. Additional experiments investigated a clinically relevant combination of LC plus gastric aspiration (combined acid and small gastric food particles) and found reductions in large surfactant aggregates in BAL similar to those for LC. However, rats given LC + combined acid and small gastric food particles versus LC had more severe surfactant dysfunction based on decreases in surface activity and alterations in large aggregate composition. Combined data for all animal groups had strong statistical correlations between surfactant dysfunction (increased minimum surface tension, decreased large aggregates in BAL, decreased aggregate PC, and increased aggregate lyso-PC) and the severity of inflammatory lung injury (increased total protein, albumin, protein/phospholipid ratio, neutrophils, and erythrocytes in BAL plus increased whole lung myeloperoxidase activity). These results show that surfactant dysfunction is important in the pathophysiology of LC with or without concurrent gastric aspiration and provides a rationale for surfactant

  3. Incidence of unanticipated difficult airway using an objective airway score versus a standard clinical airway assessment

    DEFF Research Database (Denmark)

    Nørskov, Anders Kehlet; Rosenstock, Charlotte Valentin; Wetterslev, Jørn


    the examination and registration of predictors for difficult mask ventilation with a non-specified clinical airway assessment on prediction of difficult mask ventilation.Method/Design: We cluster-randomized 28 Danish departments of anaesthesia to airway assessment either by the SARI or by usual non...... reduction equalling a number needed to treat of 180. Sample size estimation is adjusted for the study design and based on standards for randomization on cluster-level. With an average cluster size of 2,500 patients, 70,000 patients will be enrolled over a 1-year trial period. The database is programmed so...

  4. Vessel-guided Airway Tree Segmentation

    DEFF Research Database (Denmark)

    Lo, P.; Sporring, J.; Ashraf, H.;


    This paper presents a method for airway tree segmentation that uses a combination of a trained airway appearance model, vessel and airway orientation information, and region growing. We propose a voxel classification approach for the appearance model, which uses a classifier that is trained...... method is evaluated on 250 low dose computed tomography images from a lung cancer screening trial. Our experiments showed that applying the region growing algorithm on the airway appearance model produces more complete airway segmentations, leading to on average 20% longer trees, and 50% less leakage...

  5. Inflammatory bowel disease and airway diseases (United States)

    Vutcovici, Maria; Brassard, Paul; Bitton, Alain


    Airway diseases are the most commonly described lung manifestations of inflammatory bowel disease (IBD). However, the similarities in disease pathogenesis and the sharing of important environmental risk factors and genetic susceptibility suggest that there is a complex interplay between IBD and airway diseases. Recent evidence of IBD occurrence among patients with airway diseases and the higher than estimated prevalence of subclinical airway injuries among IBD patients support the hypothesis of a two-way association. Future research efforts should be directed toward further exploration of this association, as airway diseases are highly prevalent conditions with a substantial public health impact. PMID:27678355

  6. The Lung Microbiome and Airway Disease. (United States)

    Lynch, Susan V


    A growing body of literature has demonstrated relationships between the composition of the airway microbiota (mixed-species communities of microbes that exist in the respiratory tract) and critical features of immune response and pulmonary function. These studies provide evidence that airway inflammatory status and capacity for repair are coassociated with specific taxonomic features of the airway microbiome. Although directionality has yet to be established, the fact that microbes are known drivers of inflammation and tissue damage suggests that in the context of chronic inflammatory airway disease, the composition and, more importantly, the function, of the pulmonary microbiome represent critical factors in defining airway disease outcomes.

  7. Mucus hypersecretion in the airway

    Institute of Scientific and Technical Information of China (English)

    WANG Ke; WEN Fu-qiang; XU Dan


    @@ Mucus hypersecretion is a distinguishing feature of Chronic intlammation diseases,such as asthma,1chronic bronchitis.2 bronchiectasis3 and cystic fibrosis.4Mucus hypersecretion leads to impairment of mucociliary clearance,abnormal bacterial plantation,mucus plug in the airway,and dysfunction of gas exchange.5

  8. Nasal continuous positive airway pressure

    DEFF Research Database (Denmark)

    Scholze, Alexandra; Lamwers, Stephanie; Tepel, Martin;


    Obstructive sleep apnoea (OSA) is linked to increased cardiovascular risk. This risk can be reduced by nasal continuous positive airway pressure (nCPAP) treatment. As OSA is associated with an increase of several vasoconstrictive factors, we investigated whether nCPAP influences the digital volum...

  9. Airway nerves: in vitro electrophysiology. (United States)

    Fox, Alyson


    Recording the activity of single airway sensory fibres or neuronal cell bodies in vitro has allowed detailed characterisation of fibre types and membrane properties. Fibre types can be identified by their conduction velocities and further studied by the application of drugs to their receptive field. C-fibres are sensitive to mechanical stimuli and a range of irritant chemicals (bradykinin, capsaicin, low pH, platelet-activating factor), whereas Adelta-fibres are relatively insensitive to chemical stimuli and appear to correlate to the rapidly adapting receptors identified in airways in vivo. Their site of origin also differs: upper airway C-fibres arise predominantly from the jugular ganglion and Adelta-fibres from the jugular and nodose ganglia. Intracellular recording from cell bodies in the ganglia has revealed a calcium-dependent potassium current common to many putative C-fibre cell bodies. This slow after hyperpolarisation current may be inhibited by stimuli that excite and sensitise C-fibres - this could be an important mechanism underlying the sensitisation of C-fibres in airway irritability.

  10. Surfactant for pediatric acute lung injury. (United States)

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


    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.

  11. Sarcoidosis of the upper and lower airways. (United States)

    Morgenthau, Adam S; Teirstein, Alvin S


    Sarcoidosis is a systemic granulomatous disease of undetermined etiology characterized by a variable clinical presentation and disease course. Although clinical granulomatous inflammation may occur within any organ system, more than 90% of sarcoidosis patients have lung disease. Sarcoidosis is considered an interstitial lung disease that is frequently characterized by restrictive physiologic dysfunction on pulmonary function tests. However, sarcoidosis also involves the airways (large and small), causing obstructive airways disease. It is one of a few interstitial lung diseases that affects the entire length of the respiratory tract - from the nose to the terminal bronchioles - and causes a broad spectrum of airways dysfunction. This article examines airway dysfunction in sarcoidosis. The anatomical structure of the airways is the organizational framework for our discussion. We discuss sarcoidosis involving the nose, sinuses, nasal passages, larynx, trachea, bronchi and small airways. Common complications of airways disease, such as, atelectasis, fibrosis, bullous leions, bronchiectasis, cavitary lesions and mycetomas, are also reviewed.

  12. 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


    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

  13. Airway remodeling in asthma: what really matters. (United States)

    Fehrenbach, Heinz; Wagner, Christina; Wegmann, Michael


    Airway remodeling is generally quite broadly defined as any change in composition, distribution, thickness, mass or volume and/or number of structural components observed in the airway wall of patients relative to healthy individuals. However, two types of airway remodeling should be distinguished more clearly: (1) physiological airway remodeling, which encompasses structural changes that occur regularly during normal lung development and growth leading to a normal mature airway wall or as an acute and transient response to injury and/or inflammation, which ultimately results in restoration of a normal airway structures; and (2) pathological airway remodeling, which comprises those structural alterations that occur as a result of either disturbed lung development or as a response to chronic injury and/or inflammation leading to persistently altered airway wall structures and function. This review will address a few major aspects: (1) what are reliable quantitative approaches to assess airway remodeling? (2) Are there any indications supporting the notion that airway remodeling can occur as a primary event, i.e., before any inflammatory process was initiated? (3) What is known about airway remodeling being a secondary event to inflammation? And (4), what can we learn from the different animal models ranging from invertebrate to primate models in the study of airway remodeling? Future studies are required addressing particularly pheno-/endotype-specific aspects of airway remodeling using both endotype-specific animal models and "endotyped" human asthmatics. Hopefully, novel in vivo imaging techniques will be further advanced to allow monitoring development, growth and inflammation of the airways already at a very early stage in life.

  14. Amino acid-based surfactants – do they deserve more attention? (United States)

    Bordes, Romain; Holmberg, Krister


    The 20 standard amino acids (together with a few more that are not used in the biosynthesis of proteins) constitute a versatile tool box for synthesis of surfactants. Anionic, cationic and zwitterionic amphiphiles can be prepared and surfactants with several functional groups can be obtained by the proper choice of starting amino acid. This review gives examples of procedures used for preparation and discusses important physicochemical properties of the amphiphiles and how these can be taken advantage of for various applications. Micelles with a chiral surface can be obtained by self-assembly of enantiomerically pure surfactants and such supramolecular chirality can be utilized for asymmetric organic synthesis and for preparation of mesoporous materials with chiral pores. Surfactants based on amino acids with two carboxyl groups are effective chelating agents and can be used as collectors in mineral ore flotation. A surfactant based on cysteine readily oxidizes into the corresponding cystine compound, which can be regarded as a gemini surfactant. The facile and reversible cysteine-cystine transformation has been taken advantage of in the design of a switchable surfactant. A very attractive aspect of surfactants based on amino acids is that the polar head-group is entirely natural and that the linkage to the hydrophobic tail, which is often an ester or an amide bond, is easily cleaved. The rate of degradation can be tailored by the structure of the amphiphile. The ester linkage in betaine ester surfactants is particularly susceptible to alkaline hydrolysis and this surfactant type can be used as a biocide with short-lived action. This paper is not intended as a full review on the topic. Instead it highlights concepts that are unique to amino acid-based surfactants and that we believe can have practical implications.

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

    CERN Document Server

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


    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...

  16. Gene expression in asthmatic airway smooth muscle: a mixed bag. (United States)

    Pascoe, Christopher D; Swyngedouw, Nicholas E; Seow, Chun Y; Paré, Peter D


    It has long been known that airway smooth muscle (ASM) contraction contributes significantly to the reversible airflow obstruction that defines asthma. It has also been postulated that phenotypic changes in ASM contribute to the airway hyper-responsiveness (AHR) that is a characteristic feature of asthma. Although there is agreement that the mass of ASM surrounding the airways is significantly increased in asthmatic compared with non-asthmatic airways, it is still uncertain whether there are quantitative or qualitative changes in the level of expression of the genes and proteins involved in the canonical contractile pathway in ASM that could account for AHR. This review will summarize past attempts at quantifying gene expression changes in the ASM of asthmatic lungs as well as non-asthmatic ASM cells stimulated with various inflammatory cytokines. The lack of consistent findings in asthmatic samples coupled with the relative concordance of results from stimulated ASM cells suggests that changes to the contractility of ASM tissues in asthma may be dependent on the presence of an inflammatory environment surrounding the ASM layer. Removal of the ASM from this environment could explain why hypercontractility is rarely seen ex vivo.

  17. Ionotropic and Metabotropic Proton-Sensing Receptors Involved in Airway Inflammation in Allergic Asthma

    Directory of Open Access Journals (Sweden)

    Haruka Aoki


    Full Text Available An acidic microenvironment has been shown to evoke a variety of airway responses, including cough, bronchoconstriction, airway hyperresponsiveness (AHR, infiltration of inflammatory cells in the lung, and stimulation of mucus hyperproduction. Except for the participation of transient receptor potential vanilloid-1 (TRPV1 and acid-sensing ion channels (ASICs in severe acidic pH (of less than 6.0-induced cough and bronchoconstriction through sensory neurons, the molecular mechanisms underlying extracellular acidic pH-induced actions in the airways have not been fully understood. Recent studies have revealed that ovarian cancer G protein-coupled receptor 1 (OGR1-family G protein-coupled receptors, which sense pH of more than 6.0, are expressed in structural cells, such as airway smooth muscle cells and epithelial cells, and in inflammatory and immune cells, such as eosinophils and dendritic cells. They function in a variety of airway responses related to the pathophysiology of inflammatory diseases, including allergic asthma. In the present review, we discuss the roles of ionotropic TRPV1 and ASICs and metabotropic OGR1-family G protein-coupled receptors in the airway inflammation and AHR in asthma and respiratory diseases.

  18. Use of Biphasic Continuous Positive Airway Pressure in Premature Infant with Cleft Lip–Cleft Palate

    Directory of Open Access Journals (Sweden)

    Lovya George


    Full Text Available Preterm infants (PIs often require respiratory support due to surfactant deficiency. Early weaning from mechanical ventilation to noninvasive respiratory support decreases ventilation-associated irreversible lung damage. This wean is particularly challenging in PIs with cleft lip and cleft palate due to anatomical difficulties encountered in maintaining an adequate seal for positive pressure ventilation. PI with a cleft lip and palate often fail noninvasive respiratory support and require continued intubation and mechanical ventilation. We are presenting the first case report of a PI with cleft lip and palate who was managed by biphasic nasal continuous positive airway pressure.

  19. Surfactant recovery from water using foam fractionation

    Energy Technology Data Exchange (ETDEWEB)

    Tharapiwattananon, N.; Osuwan, S. [Chulalongkorn Univ., Bangkok (Thailand); Scamehorn, J.F. [Inst. of Oklahoma, Norman, OK (United States)] [and others


    The purpose of this study was to investigate the use of foam fractionation to recover surfactant from water. A simple continuous mode foam fractionation was used and three surfactants were studied (two anionic and one cationic). The effects of air flow rate, foam height, liquid height, liquid feed surfactant concentration, and sparger porosity were studied. This technique was shown to be effective in either surfactant recovery or the reduction of surfactant concentration in water to acceptable levels. As an example of the effectiveness of this technique, the cetylpyridinium chloride concentration in water can be reduced by 90% in one stage with a liquid residence time of 375 minutes. The surfactant concentration in the collapsed foam is 21.5 times the feed concentration. This cationic surfactant was easier to remove from water by foam fractionation than the anionic surfactants studied.

  20. Synthesis of carbohydrate-based surfactants

    Energy Technology Data Exchange (ETDEWEB)

    Pemberton, Jeanne E.; Polt, Robin L.; Maier, Raina M.


    The present invention provides carbohydrate-based surfactants and methods for producing the same. Methods for producing carbohydrate-based surfactants include using a glycosylation promoter to link a carbohydrate or its derivative to a hydrophobic compound.

  1. Efficient delivery of RNA interference oligonucleotides to polarized airway epithelia in vitro. (United States)

    Ramachandran, Shyam; Krishnamurthy, Sateesh; Jacobi, Ashley M; Wohlford-Lenane, Christine; Behlke, Mark A; Davidson, Beverly L; McCray, Paul B


    Polarized and pseudostratified primary airway epithelia present barriers that significantly reduce their transfection efficiency and the efficacy of RNA interference oligonucleotides. This creates an impediment in studies of the airway epithelium, diminishing the utility of loss-of-function as a research tool. Here we outline methods to introduce RNAi oligonucleotides into primary human and porcine airway epithelia grown at an air-liquid interface and difficult-to-transfect transformed epithelial cell lines grown on plastic. At the time of plating, we reverse transfect small-interfering RNA (siRNA), Dicer-substrate siRNA, or microRNA oligonucleotides into cells by use of lipid or peptide transfection reagents. Using this approach we achieve significant knockdown in vitro of hypoxanthine-guanine phosphoribosyltransferase, IL-8, and CFTR expression at the mRNA and protein levels in 1-3 days. We also attain significant reduction of secreted IL-8 in polarized primary pig airway epithelia 3 days posttransfection and inhibition of CFTR-mediated Cl⁻ conductance in polarized air-liquid interface cultures of human airway epithelia 2 wk posttransfection. These results highlight an efficient means to deliver RNA interference reagents to airway epithelial cells and achieve significant knockdown of target gene expression and function. The ability to reliably conduct loss-of-function assays in polarized primary airway epithelia offers benefits to research in studies of epithelial cell homeostasis, candidate gene function, gene-based therapeutics, microRNA biology, and targeting the replication of respiratory viruses.

  2. Effects of Concentration and Conformation of Surfactants on Phase Separation of Surfactant-Water-Oil Systems

    Institute of Scientific and Technical Information of China (English)

    袁银权; 邹宪武; 刘昊阳


    The effects of surfactants on the phase separation of surfactant-water-oil systems have been investigated by using discontinuous molecular dynamic simulations. The phase separation speed and equilibrium configuration are dependent on the surfactant concentration and conformation. The equilibrium concentration of surfactants at the interface remains constant. With the increasing surfactant concentration, the equilibrium configuration crosses over from the disperse phase to the bicontinuous one. The crossover concentration is estimated. The conformation of the surfactant has little effect on the equilibrium concentration of surfactants at the interface,while it affects the equilibrium configuration after phase separation.

  3. Complex Formation Between Polyelectrolytes and Ionic Surfactants



    The interaction between polyelectrolyte and ionic surfactant is of great importance in different areas of chemistry and biology. In this paper we present a theory of polyelectrolyte ionic-surfactant solutions. The new theory successfully explains the cooperative transition observed experimentally, in which the condensed counterions are replaced by ionic-surfactants. The transition is found to occur at surfactant densities much lower than those for a similar transition in non-ionic polymer-sur...

  4. Comparative insight into surfactants mediated amyloidogenesis of lysozyme. (United States)

    Chaturvedi, Sumit K; Khan, Javed M; Siddiqi, Mohammad K; Alam, Parvez; Khan, Rizwan H


    Electrostatic and hydrophobic interactions have an important role in the protein aggregation. In this study, we have investigated the effect of charge and hydrophobicity of oppositely charged surfactants i.e., anionic (AOT and SDS) and cationic (CTAB and DTAB) on hen egg white lysozyme at pH 9.0 and 13.0, respectively. We have employed various methods such as turbidity measurements, Rayleigh light scattering, ThT, Congo red and ANS dye binding assays, far-UV CD, atomic force microscopy, transmission electron and fluorescence microscopy. At lower molar ratio, both anionic and cationic surfactants promote amyloid fibril formation in lysozyme at pH 9.0 and 13.0, respectively. The aggregation was proportionally increased with respect to protein concentration and hydrophobicity of surfactant. The morphology of aggregates at both the pH was fibrillar in structure, as visualized by dye binding and microscopic imaging techniques. Initially, the interaction between surfactants and lysozyme was electrostatic and then hydrophobic as investigated by ITC. This study demonstrates the crucial role of charge and hydrophobicity during amyloid fibril formation.

  5. Binding of cationic surfactants to humic substances

    NARCIS (Netherlands)

    Ishiguro, M.; Tan, W.; Koopal, L.K.


    Commercial surfactants are introduced into the environment either through waste products or site-specific contamination. The amphiphilic nature of both surfactants and humic substances (HS) leads to their mutual attraction especially when surfactant and HS are oppositely charged. Binding of the cati

  6. Surfactant analysis in oil-containing fluids

    Energy Technology Data Exchange (ETDEWEB)

    Gronsveld, J.; Faber, M.J. (Koninklijke Shell Exploratie en Produktie Laboratorium, Rijswijk (Netherlands))

    The total surfactant concentration in aqueous phase samples can be analysed with a potentiometric titration. In enhanced oil recovery research, however, the surfactant is produced not only in aqueous phase samples but also in oleic phase samples. The oleic constituents in the oliec phase samples interfere in the surfactant analysis and, therefore, the titration method has been adapted. (orig.).

  7. Surfactant adsorption to soil components and soils

    NARCIS (Netherlands)

    Ishiguro, Munehide; Koopal, Luuk K.


    Soils are complex and widely varying mixtures of organic matter and inorganic materials; adsorption of surfactants to soils is therefore related to the soil composition. We first discuss the properties of surfactants, including the critical micelle concentration (CMC) and surfactant adsorption on

  8. Phospholipid bilayer-perturbing properties underlying lysis induced by pH-sensitive cationic lysine-based surfactants in biomembranes. (United States)

    Nogueira, Daniele Rubert; Mitjans, Montserrat; Busquets, M Antonia; Pérez, Lourdes; Vinardell, M Pilar


    Amino acid-based surfactants constitute an important class of natural surface-active biomolecules with an unpredictable number of industrial applications. To gain a better mechanistic understanding of surfactant-induced membrane destabilization, we assessed the phospholipid bilayer-perturbing properties of new cationic lysine-based surfactants. We used erythrocytes as biomembrane models to study the hemolytic activity of surfactants and their effects on cells' osmotic resistance and morphology, as well as on membrane fluidity and membrane protein profile with varying pH. The antihemolytic capacity of amphiphiles correlated negatively with the length of the alkyl chain. Anisotropy measurements showed that the pH-sensitive surfactants, with the positive charge on the α-amino group of lysine, significantly increased membrane fluidity at acidic conditions. SDS-PAGE analysis revealed that surfactants induced significant degradation of membrane proteins in hypo-osmotic medium and at pH 5.4. By scanning electron microscopy examinations, we corroborated the interaction of surfactants with lipid bilayer. We found that varying the surfactant chemical structure is a way to modulate the positioning of the molecule inside bilayer and, thus, the overall effect on the membrane. Our work showed that pH-sensitive lysine-based surfactants significantly disturb the lipid bilayer of biomembranes especially at acidic conditions, which suggests that these compounds are promising as a new class of multifunctional bioactive excipients for active intracellular drug delivery.

  9. Surfactant protein D in newborn infants

    DEFF Research Database (Denmark)

    Dahl, Marianne; Juvonen, Pekka Olavi; Holmskov, Uffe;


    , the highest levels being observed in infants born by cesarean section. It was concluded that SP-D concentrations in umbilical cord blood and capillary blood are highly variable and depend on several perinatal conditions. Further studies are needed to elucidate the effect of respiratory distress and infection...

  10. Airway surface liquid volume expansion induces rapid changes in amiloride-sensitive Na+ transport across upper airway epithelium-Implications concerning the resolution of pulmonary edema (United States)

    Azizi, Fouad; Arredouani, Abdelilah; Mohammad, Ramzi M


    During airway inflammation, airway surface liquid volume (ASLV) expansion may result from the movement of plasma proteins and excess liquid into the airway lumen due to extravasation and elevation of subepithelial hydrostatic pressure. We previously demonstrated that elevation of submucosal hydrostatic pressure increases airway epithelium permeability resulting in ASLV expansion by 500 μL cm−2 h−1. Liquid reabsorption by healthy airway epithelium is regulated by active Na+ transport at a rate of 5 μL cm−2 h−1. Thus, during inflammation the airway epithelium may be submerged by a large volume of luminal liquid. Here, we have investigated the mechanism by which ASLV expansion alters active epithelial Na+ transport, and we have characterized the time course of the change. We used primary cultures of tracheal airway epithelium maintained under air interface (basal ASLV, depth is 7 ± 0.5 μm). To mimic airway flooding, ASLV was expanded to a depth of 5 mm. On switching from basal to expanded ASLV conditions, short-circuit current (Isc, a measure of total transepithelial active ion transport) declined by 90% with a half-time (t1/2) of 1 h. 24 h after the switch, there was no significant change in ATP concentration nor in the number of functional sodium pumps as revealed by [3H]-ouabain binding. However, amiloride-sensitive uptake of 22Na+ was reduced by 70% upon ASLV expansion. This process is reversible since after returning cells back to air interface, Isc recovered with a t1/2 of 5–10 h. These results may have important clinical implications concerning the development of Na+ channels activators and resolution of pulmonary edema. PMID:26333829

  11. p42/p44 MAP kinase activation is localized to caveolae-free membrane domains in airway smooth muscle

    NARCIS (Netherlands)

    Gosens, Reinoud; Dueck, Gordon; Gerthoffer, William T; Unruh, Helmut; Zaagsma, Johan; Meurs, Herman; Halayko, Andrew J


    Caveolae are abundant plasma membrane invaginations in airway smooth muscle that may function as preorganized signalosomes by sequestering and regulating proteins that control cell proliferation, including receptor tyrosine kinases (RTKs) and their signaling effectors. We previously demonstrated, ho

  12. Simvastatin attenuates lipopolysaccharide-induced airway mucus hypersecretion in rats

    Institute of Scientific and Technical Information of China (English)

    OU Xue-mei; WANG Bai-ding; WEN Fu-qiang; FENG Yu-lin; HUANG Xiang-yang; XIAO Jun


    Background Mucus hypersecretion in the respiratory tract and goblet cell metaplasia in the airway epithelium contribute to the morbidity and mortality associated with airway inflammatory diseases.This study aimed to examine the effect and mechanisms of simvastatin on airway mucus hypersecretion in rats treated with lipopolysaccharide (LPS).Methods Mucus hypersecretion in rat airways was induced by intra-tracheal instillation of LPS.Rats treated with or without LPS were administered intra-peritoneally simvastatin (5 and 20 mg/kg) for 4 days.Expression of Muc5ac,RhoA and mitogen-activated protein kinases (MAPK) p38 in lung were detected by real-time polymerase chain reaction (PCR),immunohistochemistry or Western blotting.Tumor necrosis factor (TNF)-a and IL-8 in bronchoalveolar lavage fluid (BALF)were assayed by an enzyme-linked lectin assay and enzyme linked immunosorbent assay (ELISA).Results Simvastatin attenuated LPS-induced goblet cell hyperplasia in bronchial epithelium and Muc5ac hypersecretion at both the gene and protein levels in lung (P<0.05).Moreover,simvastatin inhibited neutrophil accumulation and the increased concentration of TNF-α and IL-8 in BALF follows LPS stimulation (P<0.05).The higher dose of simvastatin was associated with a more significant reduction in Muc5ac mRNA expression,neutrophil accumulation and inflammatory cytokine release.Simultaneously,the increased expression of RhoA and p38 MAPK were observed in LPS-treated lung (P<0.05).Simvastatin inhibited the expression of RhoA and p38 phosphorylation in lung following LPS stimulation (P<0.05).However,the increased expression of p38 protein in LPS-traated lung was not affected by simvastatin administration.Conclusions Simvastatin attenuates airway mucus hypersecretion and pulmonary inflammatory damage induced by LPS.The inhibitory effect of simvastatin on airway mucus hypersecretion may be through,at least in part,the suppression of neutrophil accumulation and inflammatory cytokine

  13. Angiogenesis is induced by airway smooth muscle strain. (United States)

    Hasaneen, Nadia A; Zucker, Stanley; Lin, Richard Z; Vaday, Gayle G; Panettieri, Reynold A; Foda, Hussein D


    Angiogenesis is an important feature of airway remodeling in both chronic asthma and chronic obstructive pulmonary disease (COPD). Airways in those conditions are exposed to excessive mechanical strain during periods of acute exacerbations. We recently reported that mechanical strain of human airway smooth muscle (HASM) led to an increase in their proliferation and migration. Sustained growth in airway smooth muscle in vivo requires an increase in the nutritional supply to these muscles, hence angiogenesis. In this study, we examined the hypothesis that cyclic mechanical strain of HASM produces factors promoting angiogenic events in the surrounding vascular endothelial cells. Our results show: 1) a significant increase in human lung microvascular endothelial cell (HMVEC-L) proliferation, migration, and tube formation following incubation in conditioned media (CM) from HASM cells exposed to mechanical strain; 2) mechanical strain of HASM cells induced VEGF expression and release; 3) VEGF neutralizing antibodies inhibited the proliferation, migration, and tube formations of HMVEC-L induced by the strained airway smooth muscle CM; 4) mechanical strain of HASM induced a significant increase in hypoxia-inducible factor-1alpha (HIF-1alpha) mRNA and protein, a transcription factor required for VEGF gene transcription; and 5) mechanical strain of HASM induced HIF-1alpha/VEGF through dual phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and ERK pathways. In conclusion, exposing HASM cells to mechanical strain induces signal transduction pathway through PI3K/Akt/mTOR and ERK pathways that lead to an increase in HIF-1alpha, a transcription factor required for VEGF expression. VEGF release by mechanical strain of HASM may contribute to the angiogenesis seen with repeated exacerbation of asthma and COPD.

  14. Airway injury during emergency transcutaneous airway access: a comparison at cricothyroid and tracheal sites.

    LENUS (Irish Health Repository)

    Salah, Nazar


    Oxygenation via the cricothyroid membrane (CTM) may be required in emergencies, but inadvertent tracheal cannulation may occur. In this study, we compared airway injury between the tracheal and CTM sites using different techniques for airway access.

  15. 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.

  16. Use of CPAP and surfactant therapy in newborns with respiratory distress syndrome. (United States)

    Murki, Srinivas; Deorari, Ashok; Vidyasagar, Dharmapuri


    Respiratory distress syndrome (RDS) is a major disease burden in the developing countries. Current evidence supports early continuous positive airway pressure (CPAP) use and early selective surfactant administration as the most efficacious interventions in the management of RDS, both in developed and developing countries. In developing countries, it is recommended to increase institutional deliveries and increase the coverage of antenatal steroids in women in preterm labor as preventive measures. Establishing intervention of CPAP and surfactant therapies in the Level II special care newborn units (SCNUs) and Level III units requires focus on training nursing staff and pediatricians across the board. These approaches would pave the way in optimizing the care of the preterm infants with RDS and decrease their mortality and morbidity significantly.

  17. In vivo role of platelet-derived growth factor-BB in airway smooth muscle proliferation in mouse lung. (United States)

    Hirota, Jeremy A; Ask, Kjetil; Farkas, Laszlo; Smith, Jane Ann; Ellis, Russ; Rodriguez-Lecompte, Juan Carlos; Kolb, Martin; Inman, Mark D


    Airway smooth muscle (ASM) hyperplasia in asthma likely contributes considerably to functional changes. Investigating the mechanisms behind proliferation of these cells may lead to therapeutic benefit. Platelet-derived growth factor (PDGF)-BB is a well known ASM mitogen in vitro but has yet to be directly explored using in vivo mouse models in the context of ASM proliferation and airway responsiveness. To determine the in vivo influence of PDGF-BB on gene transcripts encoding contractile proteins, ASM proliferation, and airway physiology, we used an adenovirus overexpression system and a model of chronic allergen exposure. We used adenovirus technology to selectively overexpress PDGF-BB in the airway epithelium of mice. Outcome measurements, including airway physiology, real time RT-PCR measurements, proliferating cell nuclear antigen staining, and airway smooth muscle quantification, were performed 7 days after exposure. The same outcome measurements were performed 24 hours and 4 weeks after a chronic allergen exposure model. PDGF-BB overexpression resulted in airway hyperresponsiveness, decreased lung compliance, increased airway smooth muscle cell numbers, positive proliferating cell nuclear antigen-stained airway smooth muscle cells, and a reduction in genes encoding contractile proteins. Chronic allergen exposure resulted in elevations in lung lavage PDGF-BB, which were observed in conjunction with changes in gene transcript expression encoding contractile proteins and ASM proliferation. We demonstrate for the first time in vivo that PDGF-BB induces ASM hyperplasia and changes in lung mechanics in mice and that, during periods of allergen exposure changes in lung, PDGF-BB are associated with changes in airway structure and function.

  18. IL-18 induces airway hyperresponsiveness and pulmonary inflammation via CD4+ T cell and IL-13.

    Directory of Open Access Journals (Sweden)

    Masanori Sawada

    Full Text Available IL-18 plays a key role in the pathogenesis of pulmonary inflammatory diseases including pulmonary infection, pulmonary fibrosis, lung injury and chronic obstructive pulmonary disease (COPD. However, it is unknown whether IL-18 plays any role in the pathogenesis of asthma. We hypothesized that overexpression of mature IL-18 protein in the lungs may exacerbate disease activities of asthma. We established lung-specific IL-18 transgenic mice on a Balb/c genetic background. Female mice sensitized- and challenged- with antigen (ovalbumin were used as a mouse asthma model. Pulmonary inflammation and emphysema were not observed in the lungs of naïve transgenic mice. However, airway hyperresponsiveness and airway inflammatory cells accompanied with CD4(+ T cells, CD8(+ T cells, eosinophils, neutrophils, and macrophages were significantly increased in ovalbumin-sensitized and challenged transgenic mice, as compared to wild type Balb/c mice. We also demonstrate that IL-18 induces IFN-γ, IL-13, and eotaxin in the lungs of ovalbumin-sensitized and challenged transgenic mice along with an increase in IL-13 producing CD4(+ T cells. Treatment with anti-CD4 monoclonal antibody or deletion of the IL-13 gene improves ovalbumin-induced airway hyperresponsiveness and reduces airway inflammatory cells in transgenic mice. Overexpressing the IL-18 protein in the lungs induces type 1 and type 2 cytokines and airway inflammation, and results in increasing airway hyperresponsiveness via CD4(+ T cells and IL-13 in asthma.

  19. Characterization of VAMP-2 in the lung: implication in lung surfactant secretion. (United States)

    Wang, Pengcheng; Howard, Marcia D; Zhang, Honghao; Chintagari, Narendranath Reddy; Bell, Anna; Jin, Nili; Mishra, Amarjit; Liu, Lin


    Lung surfactant is crucial for reducing the surface tension of alveolar space, thus preventing the alveoli from collapse. Lung surfactant is synthesized in alveolar epithelial type II cells and stored in lamellar bodies before being released via the fusion of lamellar bodies with the apical plasma membrane. SNAREs (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptors) play an essential role in membrane fusion. We have previously demonstrated the requirement of t-SNARE (target SNARE) proteins, syntaxin 2 and SNAP-23 (N-ethylmaleimide-sensitive factor-attachment protein 23), in regulated surfactant secretion. Here, we characterized the distribution of VAMPs (vesicle-associated membrane proteins) in rat lung and alveolar type II cells. VAMP-2, -3 and -8 are shown in type II cells at both mRNA and protein levels. VAMP-2 and -8 were enriched in LB (lamellar body) fraction. Immunochemistry studies indicated that VAMP-2 was co-localized with the LB marker protein, LB-180. Functionally, the cytoplasmic domain of VAMP-2, but not VAMP-8 inhibited surfactant secretion in type II cells. We suggest that VAMP-2 is the v-SNARE (vesicle SNARE) involved in regulated surfactant secretion.

  20. Interactions of Ovalbumin with Ionic Surfactants

    Institute of Scientific and Technical Information of China (English)

    GUO Xia; YAN Hui; GUO Rong


    The interactions of ovalbumin (OVA) with one anionic surfactant,sodium dodecyl sulfate (SDS),and two cationic surfactants,dodecyl trimethylammonium bromide (DTAB) and cetyl trimethylammonium bromide (CTAB),in water have been studied through fluorescence and UV-Vis spectroscopies and transmission electronic microscopy,combined with the measurement of conductivity.OVA can increase the critical micelle concentrations (cmc) of SDS and CTAB but has little effect on that of DTAB.The interaction between surfactant monomer and OVA is greater than that between surfactant micelles and OVA.Moreover,SDS can make OVA unfolded while cationic surfactants cannot.

  1. Airway Tree Extraction with Locally Optimal Paths

    DEFF Research Database (Denmark)

    Lo, Pechin Chien Pau; Sporring, Jon; Pedersen, Jesper Johannes Holst


    This paper proposes a method to extract the airway tree from CT images by continually extending the tree with locally optimal paths. This is in contrast to commonly used region growing based approaches that only search the space of the immediate neighbors. The result is a much more robust method...... for tree extraction that can overcome local occlusions. The cost function for obtaining the optimal paths takes into account of an airway probability map as well as measures of airway shape and orientation derived from multi-scale Hessian eigen analysis on the airway probability. Significant improvements...

  2. Anatomic Optical Coherence Tomography of Upper Airways (United States)

    Chin Loy, Anthony; Jing, Joseph; Zhang, Jun; Wang, Yong; Elghobashi, Said; Chen, Zhongping; Wong, Brian J. F.

    The upper airway is a complex and intricate system responsible for respiration, phonation, and deglutition. Obstruction of the upper airways afflicts an estimated 12-18 million Americans. Pharyngeal size and shape are important factors in the pathogenesis of airway obstructions. In addition, nocturnal loss in pharyngeal muscular tone combined with high pharyngeal resistance can lead to collapse of the airway and periodic partial or complete upper airway obstruction. Anatomical optical coherence tomography (OCT) has the potential to provide high-speed three-dimensional tomographic images of the airway lumen without the use of ionizing radiation. In this chapter we describe the methods behind endoscopic OCT imaging and processing to generate full three dimensional anatomical models of the human airway which can be used in conjunction with numerical simulation methods to assess areas of airway obstruction. Combining this structural information with flow dynamic simulations, we can better estimate the site and causes of airway obstruction and better select and design surgery for patients with obstructive sleep apnea.


    Sorbello, Massimiliano; Frova, Giulio; Zdravković, Ivana


    Airway management is basic for anesthesia practice, and sometimes it can represent a really dramatic scenario for both the patient and the physicians. Laryngoscopy has been the gold standard of airway visualization for more than 60 years, showing its limitations and failure rates with time. New technology has made available an opportunity to move the physician's eye inside patient airways thanks to video laryngoscopy and video assisted airway management technique. Undoubtedly, we have entered a new era of high resolution airway visualization and different approach in airway instrumentation. Nevertheless, each new technology needs time to be tested and considered reliable, and pitfalls and limitations may come out with careful and long lasting analysis, so it is probably not the right time yet to promote video assisted approach as a new gold standard for airway visualization, despite the fact that it certainly offers some new prospects. In any case, whatever the visualization approach, no patient dies because of missed airway visualization or failed intubation, but due to failed ventilation, which remains without doubt the gold standard of any patient safety goal and airway management technique.

  4. Cholinergic Regulation of Airway Inflammation and Remodelling

    Directory of Open Access Journals (Sweden)

    Saeed Kolahian


    Full Text Available Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway diseases. Moreover, it has become apparent that acetylcholine is synthesized by nonneuronal cells and tissues, including inflammatory cells and structural cells. In this paper, we will discuss the regulatory role of acetylcholine in inflammation and remodelling in which we will focus on the role of the airway smooth muscle cell as a target cell for acetylcholine that modulates inflammation and remodelling during respiratory diseases such as asthma and COPD.

  5. Ultrasonography in the management of the airway

    DEFF Research Database (Denmark)

    Kristensen, M S


    In this study, it is described how to use ultrasonography (US) for real-time imaging of the airway from the mouth, over pharynx, larynx, and trachea to the peripheral alveoli, and how to use this in airway management. US has several advantages for imaging of the airway - it is safe, quick...... or the esophagus by placing the ultrasound probe transversely on the neck at the level of the suprasternal notch during intubation, thus confirming intubation without the need for ventilation or circulation. US can be applied before anesthesia induction and diagnose several conditions that affect airway management...

  6. Airway smooth muscle dynamics : a common pathway of airway obstruction in asthma

    NARCIS (Netherlands)

    An, S S; Bai, T R; Bates, J H T; Black, J L; Brown, R H; Brusasco, V; Chitano, P; Deng, L; Dowell, M; Eidelman, D H; Fabry, B; Fairbank, N J; Ford, L E; Fredberg, J J; Gerthoffer, W T; Gilbert, S H; Gosens, R; Gunst, S J; Halayko, A J; Ingram, R H; Irvin, C G; James, A L; Janssen, L J; King, G G; Knight, D A; Lauzon, A M; Lakser, O J; Ludwig, M S; Lutchen, K R; Maksym, G N; Martin, J G; Mauad, T; McParland, B E; Mijailovich, S M; Mitchell, H W; Mitchell, R W; Mitzner, W; Murphy, T M; Paré, P D; Pellegrino, R; Sanderson, M J; Schellenberg, R R; Seow, C Y; Silveira, P S P; Smith, P G; Solway, J; Stephens, N L; Sterk, P J; Stewart, A G; Tang, D D; Tepper, R S; Tran, T; Wang, L


    Excessive airway obstruction is the cause of symptoms and abnormal lung function in asthma. As airway smooth muscle (ASM) is the effecter controlling airway calibre, it is suspected that dysfunction of ASM contributes to the pathophysiology of asthma. However, the precise role of ASM in the series o

  7. Pim1 kinase protects airway epithelial cells from cigarette smoke-induced damage and airway inflammation

    NARCIS (Netherlands)

    de Vries, M.; Heijink, Hilde; Gras, R.; den Boef, L. E.; Reinders-Luinge, M.; Pouwels, S. D.; Hylkema, Machteld; van der Toorn, Marco; Brouwer, U.; van Oosterhout, A. J. M.; Nawijn, M. C.


    Exposure to cigarette smoke (CS) is the main risk factor for developing chronic obstructive pulmonary disease and can induce airway epithelial cell damage, innate immune responses, and airway inflammation. We hypothesized that cell survival factors might decrease the sensitivity of airway epithelial

  8. Animal-derived surfactants for the treatment and prevention of neonatal respiratory distress syndrome: summary of clinical trials

    Directory of Open Access Journals (Sweden)

    J Wells Logan


    Full Text Available J Wells Logan, Fernando R MoyaDepartment of Neonatology, Southeast Area Health Educational Center, New Hanover Regional Medical Center, Wilmington, NC, USAIntroduction: Available literature suggests that the advantage of animal-derived surfactants over first-generation synthetic agents derives from the presence of surface-active proteins and their phospholipid content. Here we summarize the results of clinical trials comparing animal-derived surfactant preparations with other animal-derived surfactants and with both first- and second-generation synthetic surfactants.Methods: Published clinical trials of comparisons of animal-derived surfactants were summarized and compared. Comparisons emphasized differences in (1 key surfactant components attributed with efficacy and (2 differences in published outcomes.Results: For the most important outcomes, mortality and chronic lung disease, currently available natural surfactants are essentially similar in efficacy. When examining secondary outcomes (pneumothorax, ventilator weaning, and need for supplemental oxygen, it appears that both calfactant and poractant have an advantage over beractant. The weight of the evidence, especially for study design and secondary outcomes, favors the use of calfactant. However, the superiority of poractant over beractant, when the higher initial dose of poractant is used, strengthens the case for use of poractant as well.Conclusions: Clinical trials suggest that the higher surfactant protein-B content in calfactant, and perhaps the higher phospholipid content in poractant (at higher initial dose, are the factors that most likely confer the observed advantage over other surfactant preparations. Keywords: surfactant, respiratory distress syndrome, phospholipids, surfactant proteins, chronic lung disease, bronchopulmonary dysplasia

  9. Apical Localization of Zinc Transporter ZnT4 in Human Airway Epithelial Cells and Its Loss in a Murine Model of Allergic Airway Inflammation

    Directory of Open Access Journals (Sweden)

    Chiara Murgia


    Full Text Available The apical cytoplasm of airway epithelium (AE contains abundant labile zinc (Zn ions that are involved in the protection of AE from oxidants and inhaled noxious substances. A major question is how dietary Zn traffics to this compartment. In rat airways, in vivo selenite autometallographic (Se-AMG-electron microscopy revealed labile Zn-selenium nanocrystals in structures resembling secretory vesicles in the apical cytoplasm. This observation was consistent with the starry-sky Zinquin fluorescence staining of labile Zn ions confined to the same region. The vesicular Zn transporter ZnT4 was likewise prominent in both the apical and basal parts of the epithelium both in rodent and human AE, although the apical pools were more obvious. Expression of ZnT4 mRNA was unaffected by changes in the extracellular Zn concentration. However, levels increased 3-fold during growth of cells in air liquid interface cultures and decreased sharply in the presence of retinoic acid. When comparing nasal versus bronchial human AE cells, there were significant positive correlations between levels of ZnT4 from the same subject, suggesting that nasal brushings may allow monitoring of airway Zn transporter expression. Finally, there were marked losses of both basally-located ZnT4 protein and labile Zn in the bronchial epithelium of mice with allergic airway inflammation. This study is the first to describe co-localization of zinc vesicles with the specific zinc transporter ZnT4 in airway epithelium and loss of ZnT4 protein in inflamed airways. Direct evidence that ZnT4 regulates Zn levels in the epithelium still needs to be provided. We speculate that ZnT4 is an important regulator of zinc ion accumulation in secretory apical vesicles and that the loss of labile Zn and ZnT4 in airway inflammation contributes to AE vulnerability in diseases such as asthma.

  10. Effects of concentrated ambient particles on normal and hypersecretory airways in rats. (United States)

    Harkema, Jack R; Keeler, Gerald; Wagner, James; Morishita, Masako; Timm, Edward; Hotchkiss, Jon; Marsik, Frank; Dvonch, Timothy; Kaminski, Norbert; Barr, Edward


    Detroit during the summer months when particulate air pollution is usually high (July and September 2000). We monitored the outdoor air pollution in this community daily, and exposed normal and compromised rats to concentrated PM2.5 from this local urban atmosphere. Rats in the inhalation studies were exposed for 1 day or for 4 or 5 consecutive days (10 hours/day) to either filtered air (controls) or concentrated ambient particles (CAPs) delivered by a Harvard ambient fine particle concentrator. Rats were killed 24 hours after the end of the exposure. Biochemical, morphometric, and molecular techniques were used to identify airway epithelial and inflammatory responses to CAPs. Lung lobes were also either intratracheally lavaged with saline to determine cellular composition and protein in bronchoalveolar lavage fluid (BALF) or removed for analysis by inductively coupled plasma-mass spectrometry (ICPMS) to detect retention of ambient PM2.5--derived trace elements. The Harvard concentrator effectively concentrated the fine ambient particles from this urban atmosphere (10-30 times) without significantly changing the major physicochemical features of the atmospheric particles. Daily CAPs mass concentrations during the 10-hour exposure period (0800-1800) in July ranged from 16 to 895 microg/m3 and in September ranged from 81 to 755 microg/m3. In general, chemical characteristics of ambient particles were conserved through the concentrator into the exposure chamber. Single or repeated exposures to CAPs did not cause adverse effects in the nasal or pulmonary airways of healthy F344 or BN rats. In addition, CAPs-related toxicity was not observed in F344 rats pretreated with bacterial endotoxin. Variable airway responses to CAPs exposure were observed in BN rats with preexisting allergic airway disease induced by OVA sensitization and challenge. Only OVA-challenged BN rats exposed to CAPs for 5 consecutive days in September 2000 had significant increases in airway mucosubstances

  11. Spectroscopy and computational studies on the interaction of octyl, dodecyl, and hexadecyl derivatives of anionic and cationic surfactants with adenosine deaminase. (United States)

    Ajloo, Davood; Mahmoodabadi, Najmeh; Ghadamgahi, Maryam; Saboury, Ali Akbar


    Effects of sodium (octyl, dodecyl, hexadecyl) sulfate and their cationic analogous on the structure of adenosine deaminase (ADA) were investigated by fluorescence and circular dichroism spectroscopy as well as molecular dynamics simulation and docking calculation. Root-mean-square derivations, radius of gyration, solvent accessible surface area, and radial distribution function were obtained. The results showed that anionic and cationic surfactants reduce protein stability. Cationic surfactants have more effect on the ADA structure in comparison with anionic surfactants. More concentration and longer surfactants are parallel to higher denaturation. Furthermore, aggregation in the presence of anionic surfactants is more than cationic surfactants. Docking data showed that longer surfactants have more interaction energy and smaller ones bound to the active site.

  12. Accumulating evidence for increased velocity of airway smooth muscle shortening in asthmatic airway hyperresponsiveness. (United States)

    Ijpma, Gijs; Matusovsky, Oleg; Lauzon, Anne-Marie


    It remains unclear whether airway smooth muscle (ASM) mechanics is altered in asthma. While efforts have originally focussed on contractile force, some evidence points to an increased velocity of shortening. A greater rate of airway renarrowing after a deep inspiration has been reported in asthmatics compared to controls, which could result from a shortening velocity increase. In addition, we have recently shown in rats that increased shortening velocity correlates with increased muscle shortening, without increasing muscle force. Nonetheless, establishing whether or not asthmatic ASM shortens faster than that of normal subjects remains problematic. Endobronchial biopsies provide excellent tissue samples because the patients are well characterized, but the size of the samples allows only cell level experiments. Whole human lungs from transplant programs suffer primarily from poor patient characterization, leading to high variability. ASM from several animal models of asthma has shown increased shortening velocity, but it is unclear whether this is representative of human asthma. Several candidates have been suggested as responsible for increased shortening velocity in asthma, such as alterations in contractile protein expression or changes in the contractile apparatus structure. There is no doubt that more remains to be learned about the role of shortening velocity in asthma.

  13. 戒烟对吸烟致敏大鼠气道5-脂氧合酶及其mRNA表达的影响%Effects of smoke cessation on expressions of 5-lipoxygenase protein and mRNA in smoking sensitized rats airway

    Institute of Scientific and Technical Information of China (English)



    Objective To study the effect of smoking and smoke cessation on airway inflammation of asthma and put forward experimental basis for the treatment of asthma of smoking through researching the effect of smoking on the expressional levels of 5-lipoxygenase protein and mRNA in sensitized rats airway.Methods Forty male Wistar rats were divided randomly into control group,sensitized group,smoking group and smoke cessation group.The rats of latter three groups were sensitized and challenged by ovalbumin to establish the asthmatic model.From the challenged third weeks,the smoking group and smoke cessation group rats were put in the self-made fumigating box to smoke passively.The expressions of 5-lipoxygenase protein and mRNA in airway were defected using immunohistochemistry and hybridization in situ in all rats of three groups.Results ① The expressions of airway 5-lipoxygenase protein of the smoking group (32.58 ± 2.78) and the smoke cessation group (26.36 ± 2.34) were significantly higher than those of the sensitized group (21.65 ± 2.12) and the control group (15.38 ± 1.68,all P <0.01),so did the sensitized group and the control group (P <0.01).②The expression of airway 5-lipoxygenase mRNA of the smoking group (34.68 ± 2.90) and the smoke cessation group (27.16 ± 2.38) were significantly higher than those of the sensitized group (23.55 ± 2.28) and the control group (15.78±1.72,all P <0.01),so did the sensitized group and the control group (P <0.01).Conclusions Smoking can increase the expession level of 5-lipoxygenase protein and mRNA in sensitized rats airway and aggravation airway inflammation.Smoke cessation can relieve airway inflammation and is an effective measure for preventing asthma.%目的 通过研究戒烟对吸烟致敏大鼠气道5-脂氧合酶(5-LO)及其mRNA表达的影响,探讨吸烟及戒烟对支气管哮喘(简称哮喘)气道炎症的影响,为吸烟哮喘患者戒烟及治疗提供依据.方法 雄性Wistar大鼠40只,随机

  14. Analysis of pulmonary surfactant in rat lungs after inhalation of nanomaterials: Fullerenes, nickel oxide and multi-walled carbon nanotubes. (United States)

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


    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.

  15. Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma. (United States)

    An, S S; Bai, T R; Bates, J H T; Black, J L; Brown, R H; Brusasco, V; Chitano, P; Deng, L; Dowell, M; Eidelman, D H; Fabry, B; Fairbank, N J; Ford, L E; Fredberg, J J; Gerthoffer, W T; Gilbert, S H; Gosens, R; Gunst, S J; Halayko, A J; Ingram, R H; Irvin, C G; James, A L; Janssen, L J; King, G G; Knight, D A; Lauzon, A M; Lakser, O J; Ludwig, M S; Lutchen, K R; Maksym, G N; Martin, J G; Mauad, T; McParland, B E; Mijailovich, S M; Mitchell, H W; Mitchell, R W; Mitzner, W; Murphy, T M; Paré, P D; Pellegrino, R; Sanderson, M J; Schellenberg, R R; Seow, C Y; Silveira, P S P; Smith, P G; Solway, J; Stephens, N L; Sterk, P J; Stewart, A G; Tang, D D; Tepper, R S; Tran, T; Wang, L


    Excessive airway obstruction is the cause of symptoms and abnormal lung function in asthma. As airway smooth muscle (ASM) is the effecter controlling airway calibre, it is suspected that dysfunction of ASM contributes to the pathophysiology of asthma. However, the precise role of ASM in the series of events leading to asthmatic symptoms is not clear. It is not certain whether, in asthma, there is a change in the intrinsic properties of ASM, a change in the structure and mechanical properties of the noncontractile components of the airway wall, or a change in the interdependence of the airway wall with the surrounding lung parenchyma. All these potential changes could result from acute or chronic airway inflammation and associated tissue repair and remodelling. Anti-inflammatory therapy, however, does not "cure" asthma, and airway hyperresponsiveness can persist in asthmatics, even in the absence of airway inflammation. This is perhaps because the therapy does not directly address a fundamental abnormality of asthma, that of exaggerated airway narrowing due to excessive shortening of ASM. In the present study, a central role for airway smooth muscle in the pathogenesis of airway hyperresponsiveness in asthma is explored.

  16. First-order phase transition during displacement of amphiphilic biomacromolecules from interfaces by surfactant molecules. (United States)

    Ettelaie, Rammile; Dickinson, Eric; Pugnaloni, Luis


    The adsorption of surfactants onto a hydrophobic interface, already laden with a fixed number of amphiphilic macromolecules, is studied using the self consistent field calculation method of Scheutjens and Fleer. For biopolymers having unfavourable interactions with the surfactant molecules, the adsorption isotherms show an abrupt jump at a certain value of surfactant bulk concentration. Alternatively, the same behaviour is exhibited when the number of amphiphilic chains on the interface is decreased. We show that this sudden jump is associated with a first-order phase transition, by calculating the free energy values for the stable and the metastable states at both sides of the transition point. We also observe that the transition can occur for two approaching surfaces, from a high surfactant coverage phase to a low surfactant coverage one, at sufficiently close separation distances. The consequence of this finding for the steric colloidal interactions, induced by the overlap of two biopolymer + surfactant films, is explored. In particular, a significantly different interaction, in terms of its magnitude and range, is predicted for these two phases. We also consider the relevance of the current study to problems involving the competitive displacement of proteins by surfactants in food colloid systems.

  17. Adsorption of dimeric surfactants in lamellar silicates

    Energy Technology Data Exchange (ETDEWEB)

    Balcerzak, Mateusz; Pietralik, Zuzanna [Department of Macromolecular Physics, Faculty of Physics, A. Mickiewicz University, Umultowska 85, 61-614 Poznań (Poland); Domka, Ludwik [Department of Metalorganic Chemistry, Faculty of Chemistry, A. Mickiewicz University, Grunwaldzka 6, 60-780 Poznań (Poland); Skrzypczak, Andrzej [Institute of Chemical Technology, Poznań University of Technology, Berdychowo 4, 60-965 Poznań (Poland); Kozak, Maciej, E-mail: [Department of Macromolecular Physics, Faculty of Physics, A. Mickiewicz University, Umultowska 85, 61-614 Poznań (Poland)


    Highlights: • The intercalation of dimeric surfactants changed the morphology of MMT samples. • XRD indicated structures formed by surfactant molecules in interlayer space. • The four-step thermal decomposition of dimeric surfactant, confirms intercalation. - Abstract: The adsorption of different types of cationic surfactants in lamellar silicates changes their surface character from hydrophilic to hydrophobic. This study was undertaken to obtain lamellar silicates modified by a series of novel dimeric (gemini) surfactants of different length alkyl chains and to characterise these organophilised materials. Synthetic sodium montmorillonite SOMASIF® ME 100 (M) and enriched bentonite of natural origin (Nanoclay – hydrophilic bentonite®) were organophilised with dimeric (gemini) surfactants (1,1′-(1,4-butanediyl)bis(alkoxymethyl)imidazolium dichlorides). As a result of surfactant molecule adsorption in interlamellar space, the d-spacing (d{sub 001}) increased from 0.97 nm (for the anhydrous structure) to 2.04 nm. A Fourier transform infrared spectroscopy (FTIR) analysis of the modified systems reveals bands assigned to the stretching vibrations of the CH{sub 2} and CH{sub 3} groups and the scissoring vibrations of the NH group from the structure of the dimeric surfactants. Thermogravimetric (TG) and derivative thermogravimetric (DTG) studies imply a four-stage process of surfactant decomposition. Scanning electron microscopy (SEM) images provide information on the influence of dimeric surfactant intercalation into the silicate structures. Particles of the modified systems show a tendency toward the formation of irregularly shaped agglomerates.

  18. Extraction of Airways from CT (EXACT’09)

    DEFF Research Database (Denmark)

    Lo, Pechin; Ginneken, Bram van; Reinhardt, Joseph M.;


    This paper describes a framework for establishing a reference airway tree segmentation, which was used to quantitatively evaluate 15 different airway tree extraction algorithms in a standardized manner. Because of the sheer difficulty involved in manually constructing a complete reference standar...

  19. Iptakalim inhibits PDGF-BB-induced human airway smooth muscle cells proliferation and migration. (United States)

    Liu, Wenrui; Kong, Hui; Zeng, Xiaoning; Wang, Jingjing; Wang, Zailiang; Yan, Xiaopei; Wang, Yanli; Xie, Weiping; Wang, Hong


    Chronic airway diseases are characterized by airway remodeling which is attributed partly to the proliferation and migration of airway smooth muscle cells (ASMCs). ATP-sensitive potassium (KATP) channels have been identified in ASMCs. Mount evidence has suggested that KATP channel openers can reduce airway hyperresponsiveness and alleviate airway remodeling. Opening K(+) channels triggers K(+) efflux, which leading to membrane hyperpolarization, preventing Ca(2+)entry through closing voltage-operated Ca(2+) channels. Intracellular Ca(2+) is the most important regulator of muscle contraction, cell proliferation and migration. K(+) efflux decreases Ca(2+) influx, which consequently influences ASMCs proliferation and migration. As a KATP channel opener, iptakalim (Ipt) has been reported to restrain the proliferation of pulmonary arterial smooth muscle cells (PASMCs) involved in vascular remodeling, while little is known about its impact on ASMCs. The present study was designed to investigate the effects of Ipt on human ASMCs and the mechanisms underlying. Results obtained from cell counting kit-8 (CCK-8), flow cytometry and 5-ethynyl-2'-deoxyuridine (EdU) incorporation showed that Ipt significantly inhibited platelet-derived growth factor (PDGF)-BB-induced ASMCs proliferation. ASMCs migration induced by PDGF-BB was also suppressed by Ipt in transwell migration and scratch assay. Besides, the phosphorylation of Ca(2+)/calmodulin-dependent kinase II (CaMKII), extracellular regulated protein kinases 1/2 (ERK1/2), protein kinase B (Akt), and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) were as well alleviated by Ipt administration. Furthermore, we found that the inhibition of Ipt on the PDGF-BB-induced proliferation and migration in human ASMCs was blocked by glibenclamide (Gli), a selective KATP channel antagonist. These findings provide a strong evidence to support that Ipt antagonize the proliferating and migrating effects of PDGF-BB on

  20. Pentraxin 3 (PTX3 expression in allergic asthmatic airways: role in airway smooth muscle migration and chemokine production.

    Directory of Open Access Journals (Sweden)

    Jingbo Zhang

    Full Text Available BACKGROUND: Pentraxin 3 (PTX3 is a soluble pattern recognition receptor with non-redundant functions in inflammation and innate immunity. PTX3 is produced by immune and structural cells. However, very little is known about the expression of PTX3 and its role in allergic asthma. OBJECTIVES AND METHODS: We sought to determine the PTX3 expression in asthmatic airways and its function in human airway smooth muscle cells (HASMC. In vivo PTX3 expression in bronchial biopsies of mild, moderate and severe asthmatics was analyzed by immunohistochemistry. PTX3 mRNA and protein were measured by real-time RT-PCR and ELISA, respectively. Proliferation and migration were examined using (3H-thymidine incorporation, cell count and Boyden chamber assays. RESULTS: PTX3 immunoreactivity was increased in bronchial tissues of allergic asthmatics compared to healthy controls, and mainly localized in the smooth muscle bundle. PTX3 protein was expressed constitutively by HASMC and was significantly up-regulated by TNF, and IL-1β but not by Th2 (IL-4, IL-9, IL-13, Th1 (IFN-γ, or Th-17 (IL-17 cytokines. In vitro, HASMC released significantly higher levels of PTX3 at the baseline and upon TNF stimulation compared to airway epithelial cells (EC. Moreover, PTX3 induced CCL11/eotaxin-1 release whilst inhibited the fibroblast growth factor-2 (FGF-2-driven HASMC chemotactic activity. CONCLUSIONS: Our data provide the first evidence that PTX3 expression is increased in asthmatic airways. HASMC can both produce and respond to PTX3. PTX3 is a potent inhibitor of HASMC migration induced by FGF-2 and can upregulate CCL11/eotaxin-1 release. These results raise the possibility that PTX3 may play a dual role in allergic asthma.

  1. Extraction of airways from CT (EXACT’09)

    DEFF Research Database (Denmark)

    Lo, Pechin Chien Pau; Ginneken, Bram van; Reinhardt, Joseph M.


    This paper describes a framework for establishing a reference airway tree segmentation, which was used to quantitatively evaluate 15 different airway tree extraction algorithms in a standardized manner. Because of the sheer difficulty involved in manually constructing a complete reference standard...... or not it is a correctly segmented part of the airway tree. Finally, the reference airway trees are constructed by taking the union of all correctly extracted branch segments. Fifteen airway tree extraction algorithms from different research groups are evaluated on a diverse set of 20 chest computed tomography (CT) scans...... from the evaluation showed that no single algorithm could extract more than an average of 74% of the total length of all branches in the reference standard, indicating substantial differences between the algorithms. A fusion scheme that obtained superior results is presented, demonstrating...

  2. Impact of the degree of ethoxylation of the ethoxylated polysorbate nonionic surfactant on the surface self-assembly of hydrophobin-ethoxylated polysorbate surfactant mixtures. (United States)

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


    Neutron reflectivity measurements have been used to study the surface adsorption of the polyethylene sorbitan monostearate surfactant, with degrees of ethoxylation varying from 3 to 20 ethylene oxide groups, with the globular protein hydrophobin. The surface interaction between the ethoxylated polysorbate nonionic surfactants and the hydrophobin results in self-assembly at the air-solution interface in the form of a well-defined layered surface structure. The surface interaction arises from a combination of the hydrophobic interaction between the surfactant alkyl chain and the hydrophobic patch on the surface of the hydrophobin, and the hydrophilic interaction between the ethoxylated sorbitan headgroup and the hydrophilic regions on the surface of the hydrophobin. The results presented show that varying the degree of ethoxylation of the polysorbate surfactant changes the interaction between the surfactant and the hydrophobin and the packing, and hence the evolution in the resulting surface structure. The optimal degree of ethoxylation for multilayer formation is over a broad range, from of order 6 to 17 ethylene oxide groups, and for degrees of ethoxylation of 3 and 20 only monolayer adsorption of either the surfactant or the hydrophobin is observed.

  3. The Effects of Proresolution of Ellagic Acid in an Experimental Model of Allergic Airway Inflammation

    Directory of Open Access Journals (Sweden)

    Claudiney de Freitas Alves


    Full Text Available Asthma is a disease of airway inflammation characterized by airway hyperresponsiveness, eosinophilic inflammation, and hypersecretion of mucus. Ellagic acid, a compound derived from medicinal plants and fruits, has shown anti-inflammatory activity in several experimental disease models. We used the classical experimental model, in BALB/c mice, of sensibilization with ovalbumin to determine the effect of ellagic acid (10 mg/kg; oral route in the resolution of allergic airways response. Dexamethasone (1 mg/kg; subcutaneous route was used as a positive control. The control group consisted of nonimmunized mice that received challenge with ovalbumin. Ellagic acid and dexamethasone or vehicle (water were administered before or after intranasal allergen challenge. Ellagic acid accelerated the resolution of airways inflammation by decreasing total leukocytes and eosinophils numbers in the bronchoalveolar lavage fluid (BALF, the mucus production and lung inflammation in part by reducing IL-5 concentration, eosinophil peroxidase (EPO activity, and P-selectin expression, but not activator protein 1 (AP-1 and nuclear factor kappa B (NF-κB pathways. In addition, ellagic acid enhanced alveolar macrophage phagocytosis of IgG-OVA-coated beads ex vivo, a new proresolving mechanism for the clearance of allergen from the airways. Together, these findings identify ellagic acid as a potential therapeutic agent for accelerating the resolution of allergic airways inflammation.

  4. Anaerobic Biodegradation of Detergent Surfactants


    Erich Jelen; Ute Merrettig-Bruns


    Detergent surfactantscan be found in wastewater in relevant concentrations. Most of them are known as ready degradable under aerobic conditions, as required by European legislation. Far fewer surfactants have been tested so far for biodegradability under anaerobic conditions. The natural environment is predominantly aerobic, but there are some environmental compartments such as river sediments, sub-surface soil layer and anaerobic sludge digesters of wastewater treatment plants which have str...

  5. Surfactants in tribology, v.3

    CERN Document Server

    Biresaw, Girma


    The manufacture and use of almost every consumer and industrial product rely on application of advanced knowledge in surface science and tribology. These two disciplines are of critical importance in major economic sectors, such as mining, agriculture, manufacturing (including metals, plastics, wood, computers, MEMS, NEMS, appliances), construction, transportation, and medical instruments, transplants, and diagnostic devices. An up-to-date reference with contributions by experts in surface science and tribology, Surfactants in Tribology, Volume 3 discusses some of the underlying tribological a

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

    NARCIS (Netherlands)

    E.P. Eijking (Eric)


    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. A double injection ADSA-CSD methodology for lung surfactant inhibition and reversal studies. (United States)

    Saad, Sameh M I; Policova, Zdenka; Dang, Andrew; Acosta, Edgar J; Hair, Michael L; Neumann, A Wilhelm


    This paper presents a continuation of the development of a drop shape method for film studies, ADSA-CSD (Axisymmetric Drop Shape Analysis-Constrained Sessile Drop). ADSA-CSD has certain advantages over conventional methods. The development presented here allows complete exchange of the subphase of a spread or adsorbed film. This feature allows certain studies relevant to lung surfactant research that cannot be readily performed by other means. The key feature of the design is a second capillary into the bulk of the drop to facilitate addition or removal of a secondary liquid. The development will be illustrated through studies concerning lung surfactant inhibition. After forming a sessile drop of a basic lung surfactant preparation, the bulk phase can be removed and exchanged for one containing different inhibitors. Such studies mimic the leakage of plasma and blood proteins into the alveolar spaces altering the surface activity of lung surfactant in a phenomenon called surfactant inhibition. The resistance of the lung surfactant to specific inhibitors can be readily evaluated using the method. The new method is also useful for surfactant reversal studies, i.e. the ability to restore the normal surface activity of an inhibited lung surfactant film by using special additives. Results show a distinctive difference between the inhibition when an inhibitor is mixed with and when it is injected under a preformed surfactant film. None of the inhibitors studied (serum, albumin, fibrinogen, and cholesterol) were able to penetrate a preexisting film formed by the basic preparation (BLES and protasan), while all of them can alter the surface activity of such preparation when mixed with the preparation. Preliminary results show that reversal of serum inhibition can be easily achieved and evaluated using the modified methodology.

  8. Surfactant-enhanced cellulose nanocrystal Pickering emulsions. (United States)

    Hu, Zhen; Ballinger, Sarah; Pelton, Robert; Cranston, Emily D


    The effect of surfactants on the properties of Pickering emulsions stabilized by cellulose nanocrystals (CNCs) was investigated. Electrophoretic mobility, interfacial tension, confocal microscopy and three-phase contact angle measurements were used to elucidate the interactions between anionic CNCs and cationic alkyl ammonium surfactants didecyldimethylammonium bromide (DMAB) and cetyltrimethylammonium bromide (CTAB). Both surfactants were found to adsorb onto CNCs with concentration-dependent morphology. At low concentrations, individual surfactant molecules adsorbed with alkyl tails pointing outward leading to hydrophobic CNCs. At higher concentrations, above the surfactant's apparent critical micelle concentration, surfactant aggregate morphologies on CNCs were inferred and the hydrophobicity of CNCs decreased. DMAB, which has two alkyl tails, rendered the CNCs more hydrophobic than CTAB which has only a single alkyl tail, at all surfactant concentrations. The change in CNC wettability from surfactant adsorption was directly linked to emulsion properties; adding surfactant increased the emulsion stability, decreased the droplet size, and controlled the internal phase of CNC Pickering emulsions. More specifically, a double transitional phase inversion, from oil-in-water to water-in-oil and back to oil-in-water, was observed for emulsions with CNCs and increasing amounts of DMAB (the more hydrophobic surfactant). With CNCs and CTAB, no phase inversion was induced. This work represents the first report of CNC Pickering emulsions with surfactants as well as the first CNC Pickering emulsions that can be phase inverted. The ability to surface modify CNCs in situ and tailor emulsions by adding surfactants may extend the potential of CNCs to new liquid formulations and extruded/spray-dried materials.

  9. Synthetic surfactant containing SP-B and SP-C mimics is superior to single-peptide formulations in rabbits with chemical acute lung injury

    Directory of Open Access Journals (Sweden)

    Frans J. Walther


    Full Text Available Background. Chemical spills are on the rise and inhalation of toxic chemicals may induce chemical acute lung injury (ALI/acute respiratory distress syndrome (ARDS. Although the pathophysiology of ALI/ARDS is well understood, the absence of specific antidotes has limited the effectiveness of therapeutic interventions.Objectives. Surfactant inactivation and formation of free radicals are important pathways in (chemical ALI. We tested the potential of lipid mixtures with advanced surfactant protein B and C (SP-B and C mimics to improve oxygenation and lung compliance in rabbits with lavage- and chemical-induced ALI/ARDS.Methods. Ventilated young adult rabbits underwent repeated saline lung lavages or underwent intratracheal instillation of hydrochloric acid to induce ALI/ARDS. After establishment of respiratory failure rabbits were treated with a single intratracheal dose of 100 mg/kg of synthetic surfactant composed of 3% Super Mini-B (S-MB, a SP-B mimic, and/or SP-C33 UCLA, a SP-C mimic, in a lipid mixture (DPPC:POPC:POPG 5:3:2 by weight, the clinical surfactant Infasurf®, a bovine lung lavage extract with SP-B and C, or synthetic lipids alone. End-points consisted of arterial oxygenation, dynamic lung compliance, and protein and lipid content in bronchoalveolar lavage fluid. Potential mechanism of surfactant action for S-MB and SP-C33 UCLA were investigated with captive bubble surfactometry (CBS assays.Results. All three surfactant peptide/lipid mixtures and Infasurf equally lowered the minimum surface tension on CBS, and also improved oxygenation and lung compliance. In both animal models, the two-peptide synthetic surfactant with S-MB and SP-C33 UCLA led to better arterial oxygenation and lung compliance than single peptide synthetic surfactants and Infasurf. Synthetic surfactants and Infasurf improved lung function further in lavage- than in chemical-induced respiratory failure, with the difference probably due to greater capillary

  10. Remediation using trace element humate surfactant

    Energy Technology Data Exchange (ETDEWEB)

    Riddle, Catherine Lynn; Taylor, Steven Cheney; Bruhn, Debra Fox


    A method of remediation at a remediation site having one or more undesirable conditions in which one or more soil characteristics, preferably soil pH and/or elemental concentrations, are measured at a remediation site. A trace element humate surfactant composition is prepared comprising a humate solution, element solution and at least one surfactant. The prepared trace element humate surfactant composition is then dispensed onto the remediation site whereby the trace element humate surfactant composition will reduce the amount of undesirable compounds by promoting growth of native species activity. By promoting native species activity, remediation occurs quickly and environmental impact is minimal.

  11. Solubilization of Hydrophobic Dyes in Surfactant Solutions

    Directory of Open Access Journals (Sweden)

    Ali Reza Tehrani-Bagha


    Full Text Available In this paper, the use of surfactants for solubilization of hydrophobic organic dyes (mainly solvent and disperse dyes has been reviewed. The effect of parameters such as the chemical structures of the surfactant and the dye, addition of salt and of polyelectrolytes, pH, and temperature on dye solubilization has been discussed. Surfactant self-assemble into micelles in aqueous solution and below the concentration where this occurs—the critical micelle concentration (CMC—there is no solubilization. Above the CMC, the amount of solubilized dye increases linearly with the increase in surfactant concentration. It is demonstrated that different surfactants work best for different dyes. In general, nonionic surfactants have higher solubilization power than anionic and cationic surfactants. It is likely that the reason for the good performance of nonionic surfactants is that they allow dyes to be accommodated not only in the inner, hydrocarbon part of the micelle but also in the headgroup shell. It is demonstrated that the location of a dye in a surfactant micelle can be assessed from the absorption spectrum of the dye-containing micellar solution.

  12. Using biologically soft surfactants for dust suppression

    Energy Technology Data Exchange (ETDEWEB)

    Tkachenko, N.G.; Kolodiichak, V.K.; Motrii, A.E.; Severin, V.D.


    This article discusses environmental aspects of using surfactants in coal mines for dust suppression. Surfactants for underground black coal mines in the USSR are divided into three classes: so-called soft surfactants with a decomposition period from 1 to 3 days, hard surfactants with decomposition exceeding a month and an intermediary group. The decomposition process is analyzed; the role played by fermentation is stressed. Environmental effects of surfactant decomposition are evaluated. Selected surfactants tested in Soviet laboratories are described. The results of experimental use of diethanolamide as a surfactant for water injection in coal seams are evaluated. Wetting time amounts to 1 s when a 0.2% concentration is used. When surfactant concentration in water is reduced to 0.05% wetting time does not change; when concentration decreases to 0.025% wetting time increases to 3 s. Surfactant efficiency is investigated under operational conditions in a Donbass mine. Specifications of the working face, mining system and air pollution caused by a shearer loader are discussed. When diethanolamide is used dust suppression efficiency ranges from 86.4 to 90.4%. During the tests diethanolamide concentration in water was 0.05%.

  13. 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


    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

  14. Allergic airway inflammation decreases lung bacterial burden following acute Klebsiella pneumoniae infection in a neutrophil- and CCL8-dependent manner. (United States)

    Dulek, Daniel E; Newcomb, Dawn C; Goleniewska, Kasia; Cephus, Jaqueline; Zhou, Weisong; Reiss, Sara; Toki, Shinji; Ye, Fei; Zaynagetdinov, Rinat; Sherrill, Taylor P; Blackwell, Timothy S; Moore, Martin L; Boyd, Kelli L; Kolls, Jay K; Peebles, R Stokes


    The Th17 cytokines interleukin-17A (IL-17A), IL-17F, and IL-22 are critical for the lung immune response to a variety of bacterial pathogens, including Klebsiella pneumoniae. Th2 cytokine expression in the airways is a characteristic feature of asthma and allergic airway inflammation. The Th2 cytokines IL-4 and IL-13 diminish ex vivo and in vivo IL-17A protein expression by Th17 cells. To determine the effect of IL-4 and IL-13 on IL-17-dependent lung immune responses to acute bacterial infection, we developed a combined model in which allergic airway inflammation and lung IL-4 and IL-13 expression were induced by ovalbumin sensitization and challenge prior to acute lung infection with K. pneumoniae. We hypothesized that preexisting allergic airway inflammation decreases lung IL-17A expression and airway neutrophil recruitment in response to acute K. pneumoniae infection and thereby increases the lung K. pneumoniae burden. As hypothesized, we found that allergic airway inflammation decreased the number of K. pneumoniae-induced airway neutrophils and lung IL-17A, IL-17F, and IL-22 expression. Despite the marked reduction in postinfection airway neutrophilia and lung expression of Th17 cytokines, allergic airway inflammation significantly decreased the lung K. pneumoniae burden and postinfection mortality. We showed that the decreased lung K. pneumoniae burden was independent of IL-4, IL-5, and IL-17A and partially dependent on IL-13 and STAT6. Additionally, we demonstrated that the decreased lung K. pneumoniae burden associated with allergic airway inflammation was both neutrophil and CCL8 dependent. These findings suggest a novel role for CCL8 in lung antibacterial immunity against K. pneumoniae and suggest new mechanisms of orchestrating lung antibacterial immunity.

  15. Acid aspiration-induced airways hyperresponsiveness in mice. (United States)

    Allen, Gilman B; Leclair, Timothy R; von Reyn, Jessica; Larrabee, Yuna C; Cloutier, Mary E; Irvin, Charles G; Bates, Jason H T


    The role of gastroesophageal reflux and micro-aspiration as a trigger of airways hyperresponsiveness (AHR) in patients with asthma is controversial. The role of acid reflux and aspiration as a direct cause of AHR in normal subjects is also unclear. We speculated that aspiration of a weak acid with a pH (1.8) equivalent to the upper range of typical gastric contents would lead to AHR in naive mice. We further speculated that modest reductions in aspirate acidity to a level expected during gastric acid suppression therapy (pH 4.0) would impede aspiration-induced AHR. BALB/c female mice were briefly anesthetized with isoflurane and allowed to aspirate 75 microl of saline with HCl (pH 1.8, 4.0, or 7.4) or underwent sham aspiration. Mice were re-anesthetized 2 or 24 h later, underwent tracheostomy, and were coupled to a mechanical ventilator. Forced oscillations were used to periodically measure respiratory impedance (Zrs) following aerosol delivery of saline and increasing doses of methacholine to measure for AHR. Values for elastance (H), airways resistance (R(N)), and tissue damping (G) were derived from Zrs. Aspirate pH of 1.8 led to a significant overall increase in peak R(N), G, and H compared with pH 4.0 and 7.4 at 2 and 24 h. Differences between pH 7.4 and 4.0 were not significant. In mice aspirating pH 1.8 compared with controls, airway lavage fluid contained more neutrophils, higher protein, and demonstrated higher permeability. We conclude that acid aspiration triggers an acute AHR, driven principally by breakdown of epithelial barrier integrity within the airways.

  16. Inflammation and airway microbiota during cystic fibrosis pulmonary exacerbations.

    Directory of Open Access Journals (Sweden)

    Edith T Zemanick

    Full Text Available BACKGROUND: Pulmonary exacerbations (PEx, frequently associated with airway infection and inflammation, are the leading cause of morbidity in cystic fibrosis (CF. Molecular microbiologic approaches detect complex microbiota from CF airway samples taken during PEx. The relationship between airway microbiota, inflammation, and lung function during CF PEx is not well understood. OBJECTIVE: To determine the relationships between airway microbiota, inflammation, and lung function in CF subjects treated for PEx. METHODS: Expectorated sputum and blood were collected and lung function testing performed in CF subjects during early (0-3d. and late treatment (>7d. for PEx. Sputum was analyzed by culture, pyrosequencing of 16S rRNA amplicons, and quantitative PCR for total and specific bacteria. Sputum IL-8 and neutrophil elastase (NE; and circulating C-reactive protein (CRP were measured. RESULTS: Thirty-seven sputum samples were collected from 21 CF subjects. At early treatment, lower diversity was associated with high relative abundance (RA of Pseudomonas (r = -0.67, p<0.001, decreased FEV(1% predicted (r = 0.49, p = 0.03 and increased CRP (r = -0.58, p = 0.01. In contrast to Pseudomonas, obligate and facultative anaerobic genera were associated with less inflammation and higher FEV₁. With treatment, Pseudomonas RA and P. aeruginosa by qPCR decreased while anaerobic genera showed marked variability in response. Change in RA of Prevotella was associated with more variability in FEV₁ response to treatment than Pseudomonas or Staphylococcus. CONCLUSIONS: Anaerobes identified from sputum by sequencing are associated with less inflammation and higher lung function compared to Pseudomonas at early exacerbation. CF PEx treatment results in variable changes of anaerobic genera suggesting the need for larger studies particularly of patients without traditional CF pathogens.

  17. The genus Prevotella in cystic fibrosis airways. (United States)

    Field, Tyler R; Sibley, Christopher D; Parkins, Michael D; Rabin, Harvey R; Surette, Michael G


    Airway disease resulting from chronic bacterial colonization and consequential inflammation is the leading cause of morbidity and mortality in patients with Cystic Fibrosis (CF). Although traditionally considered to be due to only a few pathogens, recent re-examination of CF airway microbiology has revealed that polymicrobial communities that include many obligate anaerobes colonize lower airways. The purpose of this study was to examine Prevotella species in CF airways by quantitative culture and phenotypic characterization. Expectorated sputum was transferred to an anaerobic environment immediately following collection and examined by quantitative microbiology using a variety of culture media. Isolates were identified as facultative or obligate anaerobes and the later group was identified by 16S rRNA sequencing. Prevotella spp. represented the majority of isolates. Twelve different species of Prevotella were recovered from 16 patients with three species representing 65% of isolates. Multiple Prevotella species were often isolated from the same sputum sample. These isolates were biochemically characterized using Rapid ID 32A kits (BioMérieux), and for their ability to produce autoinducer-2 and beta-lactamases. Considerable phenotypic variability between isolates of the same species was observed. The quantity and composition of Prevotella species within a patients' airway microbiome varied over time. Our results suggest that the diversity and dynamics of Prevotella in CF airways may contribute to airway disease.

  18. Upper airway collapsibility in anesthetized children. (United States)

    Litman, Ronald S; McDonough, Joseph M; Marcus, Carole L; Schwartz, Alan R; Ward, Denham S


    We sought to establish the feasibility of measuring upper airway narrowing in spontaneously breathing, anesthetized children using dynamic application of negative airway pressure. A secondary aim was to compare differences in upper airway collapsibility after the administration of sevoflurane or halothane. Subjects were randomized to either drug for inhaled anesthetic induction. Each was adjusted to their 1 MAC value (0.9% for halothane and 2.5% for sevoflurane) and a blinded anesthesia provider held the facemask without performing manual airway opening maneuvers but with inclusion of an oral airway device. Inspiratory flows were measured during partial upper airway obstruction created by an adjustable negative pressure-generating vacuum motor inserted into the anesthesia circuit. Critical closing pressure of the pharynx (Pcrit) was obtained by plotting the peak inspiratory flow of the obstructed breaths against the corresponding negative pressure in the facemask and extrapolating to zero airflow using linear correlation. Fourteen children were enrolled, seven in each anesthetic group. Two children in the halothane group did not develop flow-limited airway obstruction despite negative pressures as low as -9 cm H2O. Pcrit for sevoflurane ranged from -6.7 to -11.6 (mean +/- sd, -9.8 +/- 1.9) cm H2O. Pcrit for halothane ranged from -8.1 to -33 (mean +/- sd, -19.4 +/- 9.3) cm H2O (sevoflurane versus halothane, P = 0.048). We conclude that when using dynamic application of negative airway pressure, halothane appears to cause less upper airway obstruction than sevoflurane at equipotent concentrations.

  19. Airway smooth muscle growth in asthma: proliferation, hypertrophy, and migration. (United States)

    Bentley, J Kelley; Hershenson, Marc B


    Increased airway smooth muscle mass is present in fatal and non-fatal asthma. However, little information is available regarding the cellular mechanism (i.e., hyperplasia vs. hypertrophy). Even less information exists regarding the functional consequences of airway smooth muscle remodeling. It would appear that increased airway smooth muscle mass would tend to increase airway narrowing and airflow obstruction. However, the precise effects of increased airway smooth muscle mass on airway narrowing are not known. This review will consider the evidence for airway smooth muscle cell proliferation and hypertrophy in asthma, potential functional effects, and biochemical mechanisms.

  20. 表面活性蛋白A及D在小鼠尿路感染中的作用及机制%Innate immunity of surfactant protein A and D in urinary tract infection with uropathogenic Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    胡凤琪; 袁海; 王桂荣; 丁国华


    目的 研究表面活性蛋白(SP)A及SP-D在尿路感染(UTI)中的作用和机制,评价SP-A及SP-D缺失对UTI的影响.方法 免疫组化评估SP-A及SP-D在野生型(WT)C57BL/6雌性小鼠肾脏内的表达及分布;Western印迹评价SP-A及SP-D双重敲除(SP-A/D KO)与WT小鼠肾脏p38磷酸化水平.应用SP-A/D KO小鼠和WT雌性小鼠构建逆行性小鼠UTI模型,小鼠分为2组:SP-MD KO+ UTI组和WT+ UTI组,分别实验24 h和48 h.进行细菌培养及计数各组肾脏及尿液中的细菌含量,HE染色评价各组病理改变;免疫组化及计数肾脏及尿液内中性粒细胞的数量.体外细菌培养观察SP-A及SP-D对致尿路感染大肠杆菌(UPEC)生长的影响.结果 WT小鼠肾脏内SP-A及SP-D主要分布于近曲小管及集合管.SP-MD KO小鼠肾脏内p38磷酸化水平显著高于WT小鼠(P<0.05).SP-A/D KO小鼠在发生UTI时,其肾脏病理改变更重,中性粒细胞浸润更多.SP-A/D KO小鼠肾脏内及尿液内细菌量在24 h及48 h均显著高于WT小鼠(均P< 0.01).体外实验显示,SP-A及SP-D均可显著抑制UPEC的生长(均P< 0.05).结论 肾脏内表达SP-A及SP-D;SP-A/D KO小鼠与WT小鼠相比,其对UTI更易感,其机制可能与UTI时炎性因子分泌不足及SP-A和SP-D对致尿路感染大肠杆菌生长的直接抑制有关.%Objective To investigate the role of surfactant protein (SP)-A and SP-D in urinary tract infection mouse model,and evaluate the effects of SP-A and SP-D absence on urinary tract infection.Methods SP-A and SP-D double knockout (SP-A/D KO) mice were made.SP-A/D KO and wild-type (WT) C57BL/6 female mice were used for this study.The expression of SP-A and SP-D in kidney was detected by immunohistochemistry (IHC).The levels of p-p38 and p38 protein in kidneys were measured by Western blotting.Uropathogenic Escherichia coli or buffer was delivered into the bladder of female mice.At 24 and 48 h after inoculation,CFU of Escherichia coli in the kidney and urine of the treated

  1. Dexamethasone inhibits repair of human airway epithelial cells mediated by glucocorticoid-induced leucine zipper (GILZ.

    Directory of Open Access Journals (Sweden)

    Jingyue Liu

    Full Text Available BACKGROUND: Glucocorticoids (GCs are a first-line treatment for asthma for their anti-inflammatory effects, but they also hinder the repair of airway epithelial injury. The anti-inflammatory protein GC-induced leucine zipper (GILZ is reported to inhibit the activation of the mitogen-activated protein kinase (MAPK-extracellular-signal-regulated kinase (ERK signaling pathway, which promotes the repair of airway epithelial cells around the damaged areas. We investigated whether the inhibition of airway epithelial repair imposed by the GC dexamethasone (DEX is mediated by GILZ. METHODS: We tested the effect of DEX on the expressions of GILZ mRNA and GILZ protein and the MAPK-ERK signaling pathway in human airway epithelial cells, via RT-PCR and Western blot. We further evaluated the role of GILZ in mediating the effect of DEX on the MAPK-ERK signaling pathway and in airway epithelium repair by utilizing small-interfering RNAs, MTT, CFSE labeling, wound-healing and cell migration assays. RESULTS: DEX increased GILZ mRNA and GILZ protein levels in a human airway epithelial cell line. Furthermore, DEX inhibited the phosphorylation of Raf-1, Mek1/2, Erk1/2 (components of the MAPK-ERK signaling pathway, proliferation and migration. However, the inhibitory effect of DEX was mitigated in cells when the GILZ gene was silenced. CONCLUSIONS: The inhibition of epithelial injury repair by DEX is mediated in part by activation of GILZ, which suppressed activation of the MAPK-ERK signaling pathway, proliferation and migration. Our study implicates the involvement of DEX in this process, and furthers our understanding of the dual role of GCs.

  2. Pharmacology of airway afferent nerve activity

    Directory of Open Access Journals (Sweden)

    Carr Michael J


    Full Text Available Abstract Afferent nerves in the airways serve to regulate breathing pattern, cough, and airway autonomic neural tone. Pharmacologic agents that influence afferent nerve activity can be subclassified into compounds that modulate activity by indirect means (e.g. bronchial smooth muscle spasmogens and those that act directly on the nerves. Directly acting agents affect afferent nerve activity by interacting with various ion channels and receptors within the membrane of the afferent terminals. Whether by direct or indirect means, most compounds that enter the airspace will modify afferent nerve activity, and through this action alter airway physiology.

  3. Hemolysis by surfactants--A review. (United States)

    Manaargadoo-Catin, Magalie; Ali-Cherif, Anaïs; Pougnas, Jean-Luc; Perrin, Catherine


    An overview of the use of surfactants for erythrocyte lysis and their cell membrane action mechanisms is given. Erythrocyte membrane characteristics and its association with the cell cytoskeleton are presented in order to complete understanding of the erythrocyte membrane distortion. Cell homeostasis disturbances caused by surfactants might induce changes starting from shape modification to cell lysis. Two main mechanisms are hypothesized in literature which are osmotic lysis and lysis by solubilization even if the boundary between them is not clearly defined. Another specific mechanism based on the formation of membrane pores is suggested in the particular case of saponins. The lytic potency of a surfactant is related to its affinity for the membrane and the modification of the lipid membrane curvature. This is to be related to the surfactant shape defined by its hydrophobic and hydrophilic moieties but also by experimental conditions. As a consequence, prediction of the hemolytic potency of a given surfactant is challenging. Several studies are focused on the relation between surfactant erythrolytic potency and their physico-chemical parameters such as the critical micellar concentration (CMC), the hydrophile-lipophile balance (HLB), the surfactant membrane/water partition coefficient (K) or the packing parameter (P). The CMC is one of the most important factors considered even if a lytic activity cut-off effect points out that the only consideration of CMC not enough predictive. The relation K.CMC must be considered in addition to the CMC to predict the surfactant lytic capacity within the same family of non ionic surfactant. Those surfactant structure/lytic activity studies demonstrate the requirement to take into account a combination of physico-chemical parameters to understand and foresee surfactant lytic potency.

  4. Airway resistance at maximum inhalation as a marker of asthma and airway hyperresponsiveness

    Directory of Open Access Journals (Sweden)

    O'Connor George T


    Full Text Available Abstract Background Asthmatics exhibit reduced airway dilation at maximal inspiration, likely due to structural differences in airway walls and/or functional differences in airway smooth muscle, factors that may also increase airway responsiveness to bronchoconstricting stimuli. The goal of this study was to test the hypothesis that the minimal airway resistance achievable during a maximal inspiration (Rmin is abnormally elevated in subjects with airway hyperresponsiveness. Methods The Rmin was measured in 34 nonasthmatic and 35 asthmatic subjects using forced oscillations at 8 Hz. Rmin and spirometric indices were measured before and after bronchodilation (albuterol and bronchoconstriction (methacholine. A preliminary study of 84 healthy subjects first established height dependence of baseline Rmin values. Results Asthmatics had a higher baseline Rmin % predicted than nonasthmatic subjects (134 ± 33 vs. 109 ± 19 % predicted, p = 0.0004. Sensitivity-specificity analysis using receiver operating characteristic curves indicated that baseline Rmin was able to identify subjects with airway hyperresponsiveness (PC20 min % predicted, FEV1 % predicted, and FEF25-75 % predicted, respectively. Also, 80% of the subjects with baseline Rmin min > 145% predicted had hyperresponsive airways, regardless of clinical classification as asthmatic or nonasthmatic. Conclusions These findings suggest that baseline Rmin, a measurement that is easier to perform than spirometry, performs as well as or better than standard spirometric indices in distinguishing subjects with airway hyperresponsiveness from those without hyperresponsive airways. The relationship of baseline Rmin to asthma and airway hyperresponsiveness likely reflects a causal relation between conditions that stiffen airway walls and hyperresponsiveness. In conjunction with symptom history, Rmin could provide a clinically useful tool for assessing asthma and monitoring response to treatment.

  5. Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yuan, E-mail:; Cardell, Lars-Olaf


    Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B{sub 2} receptor agonist) and des-Arg{sup 9}-bradykinin- (selective B{sub 1} receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE{sub 2}. The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg{sup 9}-bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B{sub 2} receptors, but not those on B{sub 1}. Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance seen in

  6. 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


    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 meas