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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 and allergic airway inflammation.

    Science.gov (United States)

    Winkler, Carla; Hohlfeld, Jens M

    2013-01-01

    Pulmonary surfactant is a complex mixture of unique proteins and lipids that covers the airway lumen. Surfactant prevents alveolar collapse and maintains airway patency by reducing surface tension at the air-liquid interface. Furthermore, it provides a defence against antigen uptake by binding foreign particles and enhancing cellular immune responses. Allergic asthma is associated with chronic airway inflammation and presents with episodes of airway narrowing. The pulmonary inflammation and bronchoconstriction can be triggered by exposure to allergens or pathogens present in the inhaled air. Pulmonary surfactant has the potential to interact with various immune cells which orchestrate allergen- or pathogen-driven episodes of airway inflammation. The complex nature of surfactant allows multiple sites of interaction, but also makes it susceptible to external alterations, which potentially impair its function. This duality of modulating airway physiology and immunology during inflammatory conditions, while at the same time being prone to alterations accompanied by restricted function, has stimulated numerous studies in recent decades, which are reviewed in this article. PMID:23896983

  3. Surfactant Protein D modulates allergen particle uptake and inflammatory response in a human epithelial airway model

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    Schleh Carsten

    2012-02-01

    Full Text Available Abstract Background Allergen-containing subpollen particles (SPP are released from whole plant pollen upon contact with water or even high humidity. Because of their size SPP can preferentially reach the lower airways where they come into contact with surfactant protein (SP-D. The aim of the present study was to investigate the influence of SP-D in a complex three-dimensional human epithelial airway model, which simulates the most important barrier functions of the epithelial airway. The uptake of SPP as well as the secretion of pro-inflammatory cytokines was investigated. Methods SPP were isolated from timothy grass and subsequently fluorescently labeled. A human epithelial airway model was built by using human Type II-pneumocyte like cells (A549 cells, human monocyte derived macrophages as well as human monocyte derived dendritic cells. The epithelial cell model was incubated with SPP in the presence and absence of surfactant protein D. Particle uptake was evaluated by confocal microscopy and advanced computer-controlled analysis. Finally, human primary CD4+ T-Cells were added to the epithelial airway model and soluble mediators were measured by enzyme linked immunosorbent assay or bead array. Results SPP were taken up by epithelial cells, macrophages, and dendritic cells. This uptake coincided with secretion of pro-inflammatory cytokines and chemokines. SP-D modulated the uptake of SPP in a cell type specific way (e.g. increased number of macrophages and epithelial cells, which participated in allergen particle uptake and led to a decreased secretion of pro-inflammatory cytokines. Conclusion These results display a possible mechanism of how SP-D can modulate the inflammatory response to inhaled allergen.

  4. 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

    2008-04-01

    Full Text Available Abstract Background The surfactant proteins B (SP-B and C (SP-C are important for the stability and function of the alveolar surfactant film. Their involvement and down-regulation in inflammatory processes has recently been proposed, but their level during neutrophilic human airway diseases are not yet known. Methods We used 1D-electrophoresis and Western blotting to determine the concentrations and molecular forms of SP-B and SP-C in bronchoalveolar lavage (BAL fluid of children with different inflammatory airway diseases. 21 children with cystic fibrosis, 15 with chronic bronchitis and 14 with pneumonia were included and compared to 14 healthy control children. Results SP-B was detected in BAL of all 64 patients, whereas SP-C was found in BAL of all but 3 children; those three BAL fluids had more than 80% neutrophils, and in two patients, who were re-lavaged later, SP-C was then present and the neutrophil count was lower. SP-B was mainly present as a dimer, SP-C as a monomer. For both qualitative and quantitative measures of SP-C and SP-B, no significant differences were observed between the four evaluated patient groups. Conclusion Concentration or molecular form of SP-B and SP-C is not altered in BAL of children with different acute and chronic inflammatory lung diseases. We conclude that there is no down-regulation of SP-B and SP-C at the protein level in inflammatory processes of neutrophilic airway disease.

  5. Protein-surfactant interactions

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    Valstar, Ank

    2000-01-01

    Protein-surfactant interactions in aqueous media have been investigated. The globular proteins lysozyme and bovine serum albumin (BSA) served as model proteins. Several ionic and non-ionic surfactants were used. Fluorescence probe measurements showed that at low sodium dodecyl sulfate (SDS) concentration (< 0.1 M) one micelle-like SDS cluster is bound to lysozyme. From dynamic light scattering (DLS) results it was observed that lysozyme in the complex does not correspond to the fully unfol...

  6. Dynamics of Surfactant Liquid Plugs at Bifurcating Lung Airway Models

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    Tavana, Hossein

    2013-11-01

    A surfactant liquid plug forms in the trachea during surfactant replacement therapy (SRT) of premature babies. Under air pressure, the plug propagates downstream and continuously divides into smaller daughter plugs at continuously branching lung airways. Propagating plugs deposit a thin film on airway walls to reduce surface tension and facilitate breathing. The effectiveness of SRT greatly depends on the final distribution of instilled surfactant within airways. To understand this process, we investigate dynamics of splitting of surfactant plugs in engineered bifurcating airway models. A liquid plug is instilled in the parent tube to propagate and split at the bifurcation. A split ratio, R, is defined as the ratio of daughter plug lengths in the top and bottom daughter airway tubes and studied as a function of the 3D orientation of airways and different flow conditions. For a given Capillary number (Ca), orienting airways farther away from a horizontal position reduced R due to the flow of a larger volume into the gravitationally favored daughter airway. At each orientation, R increased with 0.0005 surfactant distribution in airways and develop effective SRT strategies.

  7. Pulmonary Surfactant Function in Alveoli and Conducting Airways

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    Goran Enhorning

    1996-01-01

    Full Text Available Surface tension plays a very important role in aeration of the neonate's lungs. Pulmonary surfactant, which is inadequate in the premature infant, modifies surface tension during the act of breathing and is necessary for maintenance of alveolar stability. These facts led to the development of the concept that it might be possible to treat the premature infant by supplementing the infant's inadequate surfactant supply. In addition to maintaining alveolar stability, pulmonary surfactant might also be of vital importance for maintenance of small airway patency. Various conditions, most importantly asthma, might be the reason for a surfactant dysfunction to develop. This in turn might cause airway resistance to increase.

  8. BINDING ISOTHERMS SURFACTANT-PROTEINS

    OpenAIRE

    Elena Irina Moater; Cristiana Radulescu; Ionica Ionita

    2011-01-01

    The interactions between surfactants and proteins shows some similarities with interactions between surfactants and polymers, but the hydrophobic amphoteric nature of proteins and their secondary and tertiary structure components make them different from conventional polymer systems. Many studies from the past about surfactant - proteins bonding used the dialysis techniques. Other techniques used to determine the binding isotherm, included ultrafiltration, ultracentrifugation, potentiometry, ...

  9. Relationship between surfactant alterations and severity of disease in horses with recurrent airway obstruction (RAO).

    OpenAIRE

    Christmann, Undine

    2008-01-01

    Pulmonary surfactant is synthesized in the alveoli and lines the respiratory epithelium of the airways. Phospholipids, the main component of surfactant, confer it its ability to lower surface tension and to prevent alveolar collapse. Airway surfactant helps maintain smaller airway patency, improves muco-ciliary clearance, decreases bronchoconstriction, and modulates pulmonary immunity. Surfactant alterations in human asthma are therefore believed to contribute to the severity of airway obstr...

  10. Computational modeling of unsteady surfactant-laden liquid plug propagation in neonatal airways

    OpenAIRE

    Olgac, Ufuk; Muradoğlu, Metin

    2013-01-01

    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...

  11. Hydrophobic surfactant proteins and their analogues.

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    Walther, Frans J; Waring, Alan J; Sherman, Mark A; Zasadzinski, Joseph A; Gordon, Larry M

    2007-01-01

    Lung surfactant is a complex mixture of phospholipids and four surfactant-associated proteins (SP-A, SP-B, SP-C and SP-D). Its major function in the lung alveolus is to reduce surface tension at the air-water interface in the terminal airways by the formation of a surface-active film enriched in surfactant lipids, hence preventing cellular collapse during respiration. Surfactant therapy using bovine or porcine lung surfactant extracts, which contain only polar lipids and native SP-B and SP-C, has dramatically improved the therapeutic outcomes of preterm infants with respiratory distress syndrome (RDS). One important goal of surfactant researchers is to replace animal-derived therapies with fully synthetic preparations based on SP-B and SP-C, produced by recombinant technology or peptide synthesis, and reconstituted with selected synthetic lipids. Here, we review recent research developments with peptide analogues of SP-B and SP-C, designed using either the known primary sequence and three-dimensional (3D) structure of the native proteins or, alternatively, the known 3D structures of closely homologous proteins. Such SP-B and SP-C mimics offer the possibility of studying the mechanisms of action of the respective native proteins, and may allow the design of optimized surfactant formulations for specific pulmonary diseases (e.g., acute lung injury (ALI) or acute respiratory distress syndrome (ARDS)). These synthetic surfactant preparations may also be a cost-saving therapeutic approach, with better quality control than may be obtained with animal-based treatments. PMID:17575474

  12. Protein recovery from surfactant precipitation.

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    Cheng, Shu Ian; Stuckey, David C

    2011-01-01

    The recovery of lysozyme from an aqueous solution containing precipitated lysozyme-AOT complexes formed by the direct addition of sodium bis-(2-ethylhexyl) sulfosuccinate (AOT) to a lysozyme solution was studied using both solvents, and a counterionic surfactant. Ethanol,methanol and solvent mixtures dissolved the surfactant precipitate and recovered lysozyme as a solid. Recovery efficiency and protein stability varied with the type of solvent used. An entirely different method of recovery was also evaluated using a counterionic surfactant: tri-octylmethylammonium chloride (TOMAC) which bound to AOT releasing lysozyme into solution.Complete recovery (100%) of lysozyme was achieved at a molar ratio of 2:1(TOMAC:AOT), and the original protein activity was maintained in the final aqueous phase.The recovered lysozyme retained its secondary structure as observed in circular dichroism(CD) spectra. Specific activity studies show that counterionic surfactant extraction does not alter the biological activity of the enzyme. PMID:22235487

  13. Computational modeling of unsteady surfactant-laden liquid plug propagation in neonatal airways

    Science.gov (United States)

    Olgac, Ufuk; Muradoglu, Metin

    2013-07-01

    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.

  14. Keeping Lung Surfactant Where It Belongs: Protein Regulation of Two-Dimensional Viscosity

    OpenAIRE

    Alonso, Coralie; Waring, Alan; Zasadzinski, Joseph A.

    2005-01-01

    Lung surfactant causes the surface tension, γ, in the alveoli to drop to nearly zero on exhalation; in the upper airways γ is ∼30 mN/m and constant. Hence, a surface tension gradient exists between alveoli and airways that should lead to surfactant flow out of the alveoli and elimination of the surface tension gradient. However, the lung surfactant specific protein SP-C enhances the resistance to surfactant flow by regulating the ratio of solid to fluid phase in the monolayer, leading to a ja...

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

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

    2015-04-01

    Beside alveoli, surface active material plays an important role in the airway physiology. In the upper airways it primarily serves in local defense. Lower airway surfactant stabilizes peripheral airways, provides the transport and defense, has barrier and anti-edematous functions, and possesses direct relaxant effect on the smooth muscle. We tested in vitro the effect of two surfactant preparations Curosurf® and Alveofact® on the precontracted smooth muscle of intra- and extra-pulmonary airways. Relaxation was more pronounced for lung tissue strip containing bronchial smooth muscle as the primary site of surfactant effect. The study does not confirm the participation of ATP-dependent potassium channels and cAMP-regulated epithelial chloride channels known as CFTR chloride channels, or nitric oxide involvement in contractile response of smooth muscle to surfactant.By controlling wall thickness and airway diameter, pulmonary surfactant is an important component of airway physiology. Thus, surfactant dysfunction may be included in pathophysiology of asthma, COPD, or other diseases with bronchial obstruction. PMID:25583659

  16. The role of surfactant in asthma

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    Hohlfeld Jens

    2002-01-01

    Full Text Available Abstract Pulmonary surfactant is a unique mixture of lipids and surfactant-specific proteins that covers the entire alveolar surface of the lungs. Surfactant is not restricted to the alveolar compartment; it also reaches terminal conducting airways and is present in upper airway secretions. While the role of surfactant in the alveolar compartment has been intensively elucidated both in health and disease states, the possible role of surfactant in the airways requires further research. This review summarizes the current knowledge on surfactant functions regarding the airway compartment and highlights the impact of various surfactant components on allergic inflammation in asthma.

  17. Pulmonary Surfactant Function in Alveoli and Conducting Airways

    OpenAIRE

    Goran Enhorning

    1996-01-01

    Surface tension plays a very important role in aeration of the neonate's lungs. Pulmonary surfactant, which is inadequate in the premature infant, modifies surface tension during the act of breathing and is necessary for maintenance of alveolar stability. These facts led to the development of the concept that it might be possible to treat the premature infant by supplementing the infant's inadequate surfactant supply. In addition to maintaining alveolar stability, pulmonary surfactant might a...

  18. Experimental and computational investigations of surfactant physicochemical behavior during conditions emulating the opening of pulmonary airways

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    Ghadiali, Samir Nuruddin

    2000-10-01

    We have investigated the mechanical influence of surfactant physicochemical properties on the progression of a semi-infinite air bubble in a fluid filled rigid capillary. This system mimics the continual interfacial expansion dynamics that occur during the opening of collapsed pulmonary airways. The goal of this study is to ascertain the surfactant physicochemical properties that are responsible for reducing airway reopening pressures that may damage lung epithelial cells. To accomplish this goal, we have developed experimental and computational models of this system. The experimental model is used to measure the ability of various surfactants to alter the reopening pressure. The non-physiologic surfactant, SDS, is capable of reducing the interfacial stresses that elevate the reopening pressure, the main component of pulmonary surfactant, L-alpha-dipalmitoyl phosphatidylcholine (DPPC), exhibits large stresses, and the clinically relevant surfactant, Infasurf, reduces the reopening pressure but maintains a surface shear or Marangoni stress. Infasurf's behavior suggests that optimal surfactant properties will reduce the reopening pressures that may damage airway epithelial cells while maintaining the Marangoni stress that enhances airway stability. Analysis of the experimental data is based on a modification of previous theoretical models which can not simulate non-equilibrium conditions near the bubble tip. Therefore, we have developed a theoretical model of surfactant effects that is capable of simulating these non-equilibrium dynamics. The coupled governing equations for fluid mechanics, molecular transport, and interfacial dynamics, are solved using a combined boundary element, dual reciprocity boundary element, and finite difference scheme. Scaling of the governing equations yields dimensionless parameters that identify the relative importance of surfactant physicochemical properties. Independent parameter variation studies are used to investigate how individual

  19. Surfactant Protein A integrates activation signal strength to differentially modulate T cell proliferation

    OpenAIRE

    Mukherjee, Sambuddho; Giamberardino, Charles; Thomas, Joseph; Evans, Kathy; GOTO, HISATSUGU; Ledford, Julie G.; Hsia, Bethany; Pastva, Amy M.; Wright, Jo Rae

    2012-01-01

    Pulmonary surfactant lipoproteins lower the surface tension at the alveolar:airway interface of the lung and participate in host defense. Previous studies reported that surfactant protein A (SP-A) inhibits lymphocyte proliferation. We hypothesized that SP-A mediated modulation of T cell activation depends upon the strength, duration and type of lymphocyte activating signals. Modulation of T cell signal strength imparted by different activating agents ex and in vivo in different mouse models, ...

  20. A model of surfactant-induced surface tension effects on the parenchymal tethering of pulmonary airways.

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    Fujioka, Hideki; Halpern, David; Gaver, Donald P

    2013-01-18

    We developed a computational model of lung parenchyma, which is comprised of individual alveolar chamber models. Each alveolus is modeled by a truncated octahedron. Considering the force balance between the elastin and collagen fibers laying on the alveolar membrane and the pressures acting on the membrane, we computed the deformations of the parenchyma with a finite element method. We focused on the effect of surfactant on the force of parenchymal tethering an airway. As the lung inflates, the parenchyma becomes stiffer and the tethering force becomes stronger. As the alveolar surfactant concentration is reduced, the lung volume at a fixed alveolar pressure decreases, and thus, the tethering force becomes weaker. The distortion of parenchyma caused by the deformation of an airway extends widely around the airway. The displacement of parenchyma decays with distance from the airway wall, but deviates from the prediction based on a theory for a continuum material. Using results obtained from the present lung parenchyma model, we also developed a simple 1-dimensional model for parenchyma tethering force on an airway, which could be utilized for the analysis of liquid/gas transports in an axis-symmetric elastic airway. The effective shear modulus was calculated from the pressure-volume relation of parenchyma. By manipulating the pressure-volume curve, this simple model may be used to predict the parenchyma tethering force in diseased lungs. PMID:23235110

  1. Molecular dynamics of surfactant protein C

    DEFF Research Database (Denmark)

    Ramírez, Eunice; Santana, Alberto; Cruz, Anthony;

    2006-01-01

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

  2. Surfactant protein D is proatherogenic in mice

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  3. Synthetic pulmonary surfactant : Effects of surfactant proteins B and C and their analogues

    OpenAIRE

    Almlén, Andreas

    2010-01-01

    Pulmonary surfactant is a lipid/protein mixture lining the air-liquid interface in the alveoli. Its main function is to lower surface tension during respiration and thereby prevent alveolar collapse at end-expiration. Surfactant deficiency, especially common in prematurely born babies, is the main cause of respiratory distress syndrome (RDS). This disease is treated with exogenous surfactant replacement using animal-derived modified natural surfactants. Production of these i...

  4. Structural study of surfactant-dependent interaction with protein

    International Nuclear Information System (INIS)

    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

  5. Structural study of surfactant-dependent interaction with protein

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-06-24

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    Surfactant proteins A (SP-A) and D (SP-D) have been implicated in pulmonary innate immunity. The proteins are host defense lectins, belonging to the collectin family which also includes mannan-binding lectin (MBL). SP-A and SP-D are pattern-recognition molecules with the lectin domains binding...... 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...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    Surfactant protein D (SP-D) is a pattern recognition molecule of the collectin family of C-type lectins. It is found in the airways and at mucosal surfaces. SP-D is part of the innate immune system where it neutralizes and leads to elimination of microorganisms. It regulates the functions of othe...

  8. Cholesterol-mediated surfactant dysfunction is mitigated by surfactant protein A.

    Science.gov (United States)

    Hiansen, Joshua Qua; Keating, Eleonora; Aspros, Alex; Yao, Li-Juan; Bosma, Karen J; Yamashita, Cory M; Lewis, James F; Veldhuizen, Ruud A W

    2015-03-01

    The ability of pulmonary surfactant to reduce surface tension at the alveolar surface is impaired in various lung diseases. Recent animal studies indicate that elevated levels of cholesterol within surfactant may contribute to its inhibition. It was hypothesized that elevated cholesterol levels within surfactant inhibit human surfactant biophysical function and that these effects can be reversed by surfactant protein A (SP-A). The initial experiment examined the function of surfactant from mechanically ventilated trauma patients in the presence and absence of a cholesterol sequestering agent, methyl-β-cyclodextrin. The results demonstrated improved surface activity when cholesterol was sequestered in vitro using a captive bubble surfactometer (CBS). These results were explored further by reconstitution of surfactant with various concentrations of cholesterol with and without SP-A, and testing of the functionality of these samples in vitro with the CBS and in vivo using surfactant depleted rats. Overall, the results consistently demonstrated that surfactant function was inhibited by levels of cholesterol of 10% (w/w phospholipid) but this inhibition was mitigated by the presence of SP-A. It is concluded that cholesterol-induced surfactant inhibition can actively contribute to physiological impairment of the lungs in mechanically ventilated patients and that SP-A levels may be important to maintain surfactant function in the presence of high cholesterol within surfactant. PMID:25522687

  9. Identification of a cell membrane protein that binds alveolar surfactant.

    OpenAIRE

    Strayer, D. S.

    1991-01-01

    Alveolar surfactants are complex mixtures of proteins and phospholipids produced by type II alveolar cells and responsible for lowering pulmonary surface tension. The process by which surfactant is produced and exported and by which its production by pulmonary cells is regulated are not well understood. This study was designed to identify a cellular receptor for surfactant constituents. To do so, monoclonal anti-idiotypic antibodies directed against antibodies to porcine and rabbit surfactant...

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

    Science.gov (United States)

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

    2013-01-01

    Lung surfactant is a complex mixture of lipids and proteins, which is secreted from the alveolar type II epithelial cell and coats the surface of alveoli as a thin layer. It plays a crucial role in the prevention of alveolar collapse through its ability to reduce surface tension. Under normal conditions, surfactant homeostasis is maintained by balancing its release and the uptake by the type II cell for recycling and the internalization by alveolar macrophages for degradation. Little is known about how the surfactant pool is monitored and regulated. Here we show, by an analysis of gene-targeted mice exhibiting massive accumulation of surfactant, that Ig-Hepta/GPR116, an orphan receptor, is expressed on the type II cell and sensing the amount of surfactant by monitoring one of its protein components, surfactant protein D, and its deletion results in a pulmonary alveolar proteinosis and emphysema-like pathology. By a coexpression experiment with Sp-D and the extracellular region of Ig-Hepta/GPR116 followed by immunoprecipitation, we identified Sp-D as the ligand of Ig-Hepta/GPR116. Analyses of surfactant metabolism in Ig-Hepta(+/+) and Ig-Hepta(-/-) mice by using radioactive tracers indicated that the Ig-Hepta/GPR116 signaling system exerts attenuating effects on (i) balanced synthesis of surfactant lipids and proteins and (ii) surfactant secretion, and (iii) a stimulating effect on recycling (uptake) in response to elevated levels of Sp-D in alveolar space. PMID:23922714

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

    Directory of Open Access Journals (Sweden)

    Taku Fukuzawa

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

  12. Late administration of surfactant replacement therapy increases surfactant protein-B content: a randomized pilot study

    OpenAIRE

    Keller, Roberta L; MERRILL, JEFFREY D.; Black, Dennis M.; Steinhorn, Robin H.; Eichenwald, Eric C.; Durand, David J.; RYAN, RITA M.; Truog, William E; Courtney, Sherry E.; Ballard, Philip L.; Ballard, Roberta A.

    2012-01-01

    Background: Surfactant dysfunction may contribute to the development of bronchopulmonary dysplasia (BPD) in persistently ventilated preterm infants. We conducted a multicenter randomized, blinded, pilot study to assess the safety and efficacy of late administration of doses of a surfactant protein-B (SP-B)-containing surfactant (calfactant) in combination with prolonged inhaled nitric oxide (iNO) in infants ≤1,000 g birth weight (BW). Methods: We randomized 85 preterm infants ventilated at 7–...

  13. CALPAIN AND MARCKS PROTEIN REGULATION OF AIRWAY MUCIN SECRETION

    OpenAIRE

    Lampe, W. Randall; Park, Joungjoa; Fang, Shijing; Crews, Anne L; Adler, Kenneth B.

    2012-01-01

    Hypersecretion of mucin plays an important role in the pathophysiology of many inflammatory airway diseases, including asthma, chronic bronchitis, and cystic fibrosis. Myristoylated alanine-rich C-kinase substrate (MARCKS) protein has been shown to play an important role in regulation of airway mucin secretion, as peptides analogous to the amino (N)-terminus of MARCKS attenuate mucin secretion by airway epithelium in vitro and in vivo. Here, we investigated a potential role for the protease C...

  14. Fluorescently labeled pulmonary surfactant protein C in spread phospholipid monolayers.

    OpenAIRE

    Nag, K.; Perez-Gil, J.; Cruz, A; Keough, K M

    1996-01-01

    Pulmonary surfactant, a lipid-protein complex, secreted into the fluid lining of lungs prevents alveolar collapse at low lung volumes. Pulmonary surfactant protein C (SP-C), an acylated, hydrophobic, alpha-helical peptide, enhances the surface activity of pulmonary surfactant lipids. Fluorescein-labeled SP-C (F-SP-C) (3, 6, 12 wt%) in dipalmitoylphosphatidylcholine (DPPC), and DPPC:dipalmitoylphosphatidylglycerol (DPPG) [DPPC:DPPG 7:3 mol/mol] in spread monolayers was studied by epifluorescen...

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

    OpenAIRE

    Boerboom, F.J.G.

    2000-01-01

    The research described in this thesis covers a number of aspects of the relation between surface properties and foaming properties of proteins, low molecular surfactants and mixtures thereof. This work is the result of a question of the industrial partners if it is possible to understand the foaming properties of protein hydrolysates. As there are many aspects of the surface properties that can be responsible for the foaming behaviour a number of problems were defined by which we can obtain a...

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Surfactant protein D in newborn infants

    DEFF Research Database (Denmark)

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

    2005-01-01

    Surfactant protein D (SP-D) is a collectin that plays an important role in the innate immune system. The role of SP-D in the metabolism of surfactant is as yet quite unclear. The aims of this study were to establish normal values of SP-D in the umbilical cord blood and capillary blood of mature...... newborn infants and to assess the influence of perinatal conditions on these levels. A total of 458 infants were enrolled in the present study. Umbilical cord blood was drawn at the time of birth and capillary blood at age 4 to 10 d. The concentration of SP-D in umbilical cord blood and capillary blood...... was measured by enzyme-linked immunosorbent assay. The median concentration of SP-D in umbilical cord blood was 392.1 ng/mL and was found to be influenced by maternal smoking and labor. The median concentration of SP-D in capillary blood was 777.5 ng/mL and was found to be influenced by the mode of delivery...

  18. Accumulation of surfactant protein D in human pulmonary alveolar proteinosis.

    OpenAIRE

    Crouch, E; Persson, A.; Chang, D.

    1993-01-01

    Surfactant protein D (SP-D) is a collagenous calcium-dependent carbohydrate-binding protein that is structurally related to the serum mannose-binding proteins and pulmonary surfactant protein A. SP-D was initially characterized as a biosynthetic product of freshly isolated rat type II cells and first purified in chemical amounts from bronchoalveolar lavage of rats with silica-induced alveolar lipoproteinosis. The present studies describe the characterization of human SP-D isolated from therap...

  19. Surfactant protein D is proatherogenic in mice

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  20. Thermodynamic effects of the hydrophobic surfactant proteins on the early adsorption of pulmonary surfactant.

    OpenAIRE

    Schram, V.; Hall, S B

    2001-01-01

    We determined the influence of the two hydrophobic proteins, SP-B and SP-C, on the thermodynamic barriers that limit adsorption of pulmonary surfactant to the air-water interface. We compared the temperature and concentration dependence of adsorption, measured by monitoring surface tension, between calf lung surfactant extract (CLSE) and the complete set of neutral and phospholipids (N&PL) without the proteins. Three stages generally characterized the various adsorption isotherms: an initial ...

  1. Surfactant Proteins in Smoking-Related Lung Disease.

    Science.gov (United States)

    Papaioannou, Andriana I; Papiris, Spyridon; Papadaki, Georgia; Manali, Effrosyni D; Roussou, Aneza; Spathis, Aris; Karakitsos, Petros; Kostikas, Konstantinos

    2016-01-01

    Pulmonary surfactant is a highly surface-active mixture of proteins and lipids that is synthesized and secreted in the alveoli by type II epithelial cells and is found in the fluid lining the alveolar surface. The protein part of surfactant constitutes two hydrophilic proteins (SP-A and SP-D) that regulate surfactant metabolism and have immunologic functions, and two hydrophobic proteins (SP-B and SP-C), which play a direct role in the organization of the surfactant structure in the interphase and in the stabilization of the lipid layers during the respiratory cycle. Several studies have shown that cigarette smoke seems to affect, in several ways, both surfactant homeostasis and function. The alterations in surfactants' biophysical properties caused by cigarette smoking, contribute to the development of several smoking related lung diseases. In this review we provide information on biochemical and physiological aspects of the pulmonary surfactant and on its possible association with the development of two major chronic diseases of the lung known to be related to smoking, i.e. chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Additional information on the possible role of surfactant protein alterations and/or dysfunction in the combination of these two conditions, recently described as combined pulmonary fibrosis and emphysema (CPFE) are also provided. PMID:26420367

  2. Pulmonary Surfactant: An Immunological Perspective

    OpenAIRE

    Chroneos, Zissis C.; Sever-Chroneos, Zvjezdana; Shepherd, Virginia L.

    2009-01-01

    Pulmonary surfactant has two crucial roles in respiratory function; first, as a biophysical entity it reduces surface tension at the air water interface, facilitating gas exchange and alveolar stability during breathing, and, second, as an innate component of the lung's immune system it helps maintain sterility and balance immune reactions in the distal airways. Pulmonary surfactant consists of 90% lipids and 10% protein. There are four surfactant proteins named SP-A, SP-B, SP-C, and SP-D; th...

  3. Lung Surfactant Levels are Regulated by Ig-Hepta/GPR116 by Monitoring Surfactant Protein D

    OpenAIRE

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

    2013-01-01

    Lung surfactant is a complex mixture of lipids and proteins, which is secreted from the alveolar type II epithelial cell and coats the surface of alveoli as a thin layer. It plays a crucial role in the prevention of alveolar collapse through its ability to reduce surface tension. Under normal conditions, surfactant homeostasis is maintained by balancing its release and the uptake by the type II cell for recycling and the internalization by alveolar macrophages for degradation. Little is known...

  4. Pulmonary surfactant proteins and polymer combinations reduce surfactant inhibition by serum

    OpenAIRE

    Lu, Karen W.; Pérez-Gil, Jesús; Echaide, Mercedes; Taeusch, H. William

    2011-01-01

    Acute respiratory distress syndrome (ARDS) is an inflammatory condition that can be associated with capillary leak of serum into alveoli causing inactivation of surfactant. Resistance to inactivation is affected by types and concentrations of surfactant proteins, lipids, and polymers. Our aim was to investigate the effects of different combinations of these three components. A simple lipid mixture (DPPC/POPG) or a more complex lipid mixture (DPPC/POPC/POPG/cholesterol) was used. Native surfac...

  5. Palmitoylation and amyloid fibril formation of lung surfactant protein C

    OpenAIRE

    Gustafsson, Magnus

    2000-01-01

    Lung surfactant is a mixture of lipids and a few proteins, of which surfactant proteins (SP)-B and SP-C are lipophilic. Surfactant is essential for the reduction of surface tension at the alveolar air/liquid interface. The extremely hydrophobic SP-C is a 35-residue transmembraneous [alpha]-helical peptide containing a poly-Val stretch and two palmitoylated Cys residues. In this thesis the structural and functional importance of the SP-C palmitoyl groups and the poly-Val heli...

  6. Lung Surfactant Protein D (SP-D) Response and Regulation During Acute and Chronic Lung Injury

    DEFF Research Database (Denmark)

    Gaunsbaek, Maria Quisgaard; Rasmussen, Karina Juhl; Beers, Michael F.;

    2013-01-01

    lung injury, with a sustained increment during chronic inflammation compared with acute inflammation. A quick upregulation of SP-D in serum in response to acute airway inflammation supports the notion that SP-D translocates from the airways into the vascular system, in favor of being synthesized......BACKGROUND: Surfactant protein D (SP-D) is a collection that plays important roles in modulating host defense functions and maintaining phospholipid homeostasis in the lung. The aim of current study was to characterize comparatively the SP-D response in bronchoalveolar lavage (BAL) and serum in...... three murine models of lung injury, using a validated ELISA technology for estimation of SP-D levels. METHODS: Mice were exposed to lipopolysaccharide, bleomycin, or Pneumocystis carinii (Pc) and sacrificed at different time points. RESULTS: In lipopolysaccharide-challenged mice, the level of SP-D in...

  7. Alpha-1-antitrypsin studies: canine serum and canine surfactant protein

    International Nuclear Information System (INIS)

    Canine serum alpha-1-antitrypsin was isolated by gel filtration and affinity chromatography and characterized by polyacrylamide gel electrophoresis and immunoelectrophoresis. Measurement of the trypsin inhibitory capacity of the separated protein indicated a ninefold concentration of functional trypsin inhibitor during the isolation procedure. Electrophoresis demonstrated the presence of a single protein with alpha-globulin mobility and a molecular weight near that of human alpha-1-antitrypsin. The trypsin inhibitory capacity of pulmonary surfactant protein from five Beagle dogs was measured, related to total surfactant protein concentration, and compared with similar measurements on whole serum from the same animals. Results indicated a variable concentration of trypsin inhibitor in the canine pulmonary surfactant protein. However, the concentration in the surfactant protein was always significantly higher than that in the corresponding serum sample. Preliminary experiments designed to separate the trypsin inhibitory fraction(s) from the other surfactant proteins by gel filtration chromatography indicated that the trypsin inhibitor was probably a single protein with a molecular weight near that of alpha-1-antitrypsin. (U.S.)

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

    International Nuclear Information System (INIS)

    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

  9. The Role of CLCA Proteins in Inflammatory Airway Disease

    Science.gov (United States)

    Patel, Anand C.; Brett, Tom J.; Holtzman, Michael J.

    2014-01-01

    Inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) exhibit stereotyped traits that are variably expressed in each person. In experimental mouse models of chronic lung disease, these individual disease traits can be genetically segregated and thereby linked to distinct determinants. Functional genomic analysis indicates that at least one of these traits, mucous cell metaplasia, depends on members of the calcium-activated chloride channel (CLCA) gene family. Here we review advances in the biochemistry of the CLCA family and the evidence of a role for CLCA family members in the development of mucous cell metaplasia and possibly airway hyperreactivity in experimental models and in humans. Based on this information, we develop the model that CLCA proteins are not integral membrane proteins with ion channel function, but instead are secreted signaling molecules that specifically regulate airway target cells in healthy and disease conditions. PMID:18954282

  10. Comparative Evaluation of Heterologous Production Systems for Recombinant Pulmonary Surfactant Protein D

    OpenAIRE

    Salgado, Daniela; Fischer, Rainer; Schillberg, Stefan; Twyman, Richard M.; Rasche, Stefan

    2014-01-01

    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 comp...

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

    OpenAIRE

    Daniela eSalgado; Rainer eFischer; Stefan eSchillberg; Twyman, Richard M.; Stefan eRasche

    2014-01-01

    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 comp...

  12. NMR spectroscopy of proteins encapsulated in a positively charged surfactant.

    Science.gov (United States)

    Lefebvre, Brian G; Liu, Weixia; Peterson, Ronald W; Valentine, Kathleen G; Wand, A Joshua

    2005-07-01

    Traditionally, large proteins, aggregation-prone proteins, and membrane proteins have been difficult to examine by modern multinuclear and multidimensional solution NMR spectroscopy. A major limitation presented by these protein systems is that their slow molecular reorientation compromises many aspects of the more powerful solution NMR methods. Several approaches have emerged to deal with the various spectroscopic difficulties arising from slow molecular reorientation. One of these takes the approach of actively seeking to increase the effective rate of molecular reorientation by encapsulating the protein of interest within the protective shell of a reverse micelle and dissolving the resulting particle in a low viscosity fluid. Since the encapsulation is largely driven by electrostatic interactions, the preparation of samples of acidic proteins suitable for NMR spectroscopy has been problematic owing to the paucity of suitable cationic surfactants. Here, it is shown that the cationic surfactant CTAB may be used to prepare samples of encapsulated anionic proteins dissolved in low viscosity solvents. In a more subtle application, it is further shown that this surfactant can be employed to encapsulate a highly basic protein, which is completely denatured upon encapsulation using an anionic surfactant. PMID:15949753

  13. Structural characterisation of human proteinosis surfactant protein A

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  14. A Function of Lung Surfactant Protein SP-B

    Science.gov (United States)

    Longo, M. L.; Bisagno, A. M.; Zasadzinski, J. A. N.; Bruni, R.; Waring, A. J.

    1993-07-01

    The primary function of lung surfactant is to form monolayers at the alveolar interface capable of lowering the normal surface tension to near zero. To accomplish this process, the surfactant must be capable of maintaining a coherent, tightly packed monolayer that avoids collapse during expiration. The positively charged amino-terminal peptide SP-B1-25 of lung surfactant-specific protein SP-B increases the collapse pressure of an important component of lung surfactant, palmitic acid (PA), to nearly 70 millinewtons per meter. This alteration of the PA isotherms removes the driving force for "squeeze-out" of the fatty acids from the primarily dipalmitoylphosphatidylcholine monolayers of lung surfactant. An uncharged mutant of SP-B1-25 induced little change in the isotherms, suggesting that a specific charge interaction between the cationic peptide and the anionic lipid is responsible for the stabilization. The effect of SP-B1-25 on fatty acid isotherms is remarkably similar to that of simple poly-cations, suggesting that such polymers might be useful as components of replacement surfactants for the treatment of respiratory distress syndrome.

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

    Directory of Open Access Journals (Sweden)

    Julie G Ledford

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

  16. Spatial and temporal expression of surfactant proteins in hyperoxia-induced neonatal rat lung injury

    Directory of Open Access Journals (Sweden)

    Walther Frans J

    2006-04-01

    Full Text Available Abstract Background Bronchopulmonary dysplasia, a complex chronic lung disease in premature children in which oxidative stress and surfactant deficiency play a crucial role, is characterized by arrested alveolar and vascular development of the immature lung. The spatial and temporal patterns of expression of surfactant proteins are not yet fully established in newborn infants and animal models suffering from BPD. Methods We studied the mRNA expression of surfactant proteins (SP A, -B, -C and -D and Clara cell secretory protein (CC10 with RT-PCR and in situ hybridization and protein expression of CC10, SP-A and -D with immunohistochemistry in the lungs of a preterm rat model, in which experimental BPD was induced by prolonged oxidative stress. Results Gene expression of all surfactant proteins (SP-A, -B, -C and -D was high at birth and initially declined during neonatal development, but SP-A, -B, and -D mRNA levels increased during exposure to hyperoxia compared to room-air controls. Peak levels were observed in adult lungs for SP-A, SP-C and CC10. Except for SP-A, the cellular distribution of SP-B, -C, -D and CC10, studied with in situ hybridization and/or immunohistochemistry, did not change in room air nor in hyperoxia. Exposure to normoxia was associated with high levels of SP-A mRNA and protein in alveolar type 2 cells and low levels in bronchial Clara cells, whereas hyperoxia induced high levels of SP-A expression in bronchial Clara cells. Conclusion The increased expression of SP-A mRNA under hyperoxia can be attributed, at least in part, to an induction of mRNA and protein expression in bronchial Clara cells. The expanded role of Clara cells in the defence against hyperoxic injury suggests that they support alveolar type 2 cell function and may play an important role in the supply of surfactant proteins to the lower airways.

  17. Role of surfactant protein A in non-infectious lung diseases.

    Science.gov (United States)

    Goto, Hisatsugu; Mitsuhashi, Atsushi; Nishioka, Yasuhiko

    2014-01-01

    Surfactant protein A (SP-A) is a large multimeric protein found in the airways and alveoli of the lungs. SP-A is a member of the collectin family of proteins, characterized by NH2-terminal collagen-like regions and COOH-terminal lectin domains. Although other surfactant proteins such as SP-B function to reduce surface tension in the lungs, SP-A as well as SP-D regulates the pulmonary immune response. To date, a number of studies have shown the immunoregulatory function of SP-A, mainly in the field of infectious diseases. By binding to a wide variety of pathogens, SP-A opsonizes and enhances pathogen uptake by phagocytes. In addition to the effect on pathogens, recent studies have shown that SP-A also modulates lung immune system in the area of non-infectious lung diseases. In this review, the potential role of SP-A in the multiple aspects of pulmonary host defense will be discussed, focusing mainly on non-infectious lung diseases such as acute and chronic pulmonary fibrosis and lung cancer. J. Med. Invest. 61: 1-6, February, 2014. PMID:24705741

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    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...

  19. Structural characterization of human and bovine lung surfactant protein D

    DEFF Research Database (Denmark)

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

    1999-01-01

    Human and bovine surfactant proteins D (SP-D) were purified from late amniotic fluid and bronchioalveolar lavage on the basis of its Ca(2+)-dependent affinity for maltose. The molecular mass of a trimeric subunit was determined by matrix-assisted laser desorption ionization MS to lie in the range...

  20. Porcine lung surfactant protein B gene (SFTPB)

    DEFF Research Database (Denmark)

    Cirera Salicio, Susanna; Fredholm, Merete

    2008-01-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...

  2. Surfactant protein D in atopic dermatitis and psoriasis

    DEFF Research Database (Denmark)

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

    2006-01-01

    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...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    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...

  5. Impact of C-reactive protein (CRP) on surfactant function

    International Nuclear Information System (INIS)

    Plasma levels of the acute-phase reactant, C-reactive protein (CRP), increase up to one thousand-fold as a result of trauma or inflammation. CRP binds to phosphorylcholine (PC) in a calcium-ion dependent manner. The structural homology between PC and the major phospholipid component of surfactant, dipalmitoyl phosphatidylcholine (DPPC), led to the present study in which we examined if CRP levels might be increased in patients with adult respiratory distress syndrome (ARDS), and subsequently interfere with surfactant function. Our results showed that CRP levels in the bronchoalveolar fluid (BALF) was increased in patients with ARDS (97.8 +/- 84.2 micrograms/mg total protein vs. 4.04 +/- 2.2 micrograms/mg total protein in normals). Our results show that CRP binds to liposomes containing DPPC and phosphatidylglycerol (PG). As a result of this interaction, CRP inhibits the surface activity of a PG-DPPC mixture when tested with a Wilhelmy surfactometer or with the Enhorning pulsating bubble apparatus. Furthermore, the surface activity of a clinically used surfactant replacement, Surfactant TA (2 mg/ml), was also severely impaired by CRP in a dose-dependent manner (doses used ranging from 24.5 to 1,175 micrograms/ml). In contrast, human serum albumin (HSA) at 500 and 900 micrograms/ml had no inhibitory effect on Surfactant TA surface activity. These results suggest that CRP, although not an initiating insult in ARDS, may contribute to the subsequent abnormalities of surfactant function and thus the pathogenesis of the pulmonary dysfunction seen in ARDS

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    The purpose of this study was to investigate how surfactant membranes can be perturbed by C-reactive protein (CRP) and whether surfactant protein A (SP-A) might overcome CRP-induced surfactant membrane alterations. The effect of CRP on surfactant surface adsorption was evaluated in vivo after...... intratracheal instillation of CRP into rat lungs. Insertion of CRP into surfactant membranes was investigated through monolayer techniques. The effect of CRP on membrane structure was studied through differential scanning calorimetry and fluorescence spectroscopy and microscopy using large and giant unilamellar...... vesicles. Our results indicate that CRP inserts into surfactant membranes and drastically increases membrane fluidity, resulting in surfactant inactivation. At 10% CRP/phospholipid weight ratio, CRP causes disappearance of liquid-ordered/liquid-disordered phase coexistence distinctive of surfactant...

  7. Stabilizing and destabilizing protein surfactant-based foams in the presence of a chemical surfactant: Effect of adsorption kinetics.

    Science.gov (United States)

    Li, Huazhen; Le Brun, Anton P; Agyei, Dominic; Shen, Wei; Middelberg, Anton P J; He, Lizhong

    2016-01-15

    Stimuli-responsive protein surfactants promise alternative foaming materials that can be made from renewable sources. However, the cost of protein surfactants is still higher than their chemical counterparts. In order to reduce the required amount of protein surfactant for foaming, we investigated the foaming and adsorption properties of the protein surfactant, DAMP4, with addition of low concentrations of the chemical surfactant sodium dodecylsulfate (SDS). The results show that the small addition of SDS can enhance foaming functions of DAMP4 at a lowered protein concentration. Dynamic surface tension measurements suggest that there is a synergy between DAMP4 and SDS which enhances adsorption kinetics of DAMP4 at the initial stage of adsorption (first 60s), which in turn stabilizes protein foams. Further interfacial properties were revealed by X-ray reflectometry measurements, showing that there is a re-arrangement of adsorbed protein-surfactant layer over a long period of 1h. Importantly, the foaming switchability of DAMP4 by metal ions is not affected by the presence of SDS, and foams can be switched off by the addition of zinc ions at permissive pH. This work provides fundamental knowledge to guide formulation using a mixture of protein and chemical surfactants towards a high performance of foaming at a low cost. PMID:26433478

  8. Green Production of Anionic Surfactant Obtained from Pea Protein

    OpenAIRE

    Rondel, Caroline; Portet, Bénédicte; Alric, Isabelle; Mouloungui, Zephirin; Blanco, Jean-François; Silvestre, Françoise

    2011-01-01

    A pea protein isolate was hydrolyzed by a double enzyme treatment method in order to obtain short peptide sequences used as raw materials to produce lipopeptides-based surfactants. Pea protein hydrolysates were prepared using the combination of Alcalase and Flavourzyme. The influence of the process variables was studied to optimize the proteolytic degradation to high degrees of hydrolysis. The average peptide chain lengths were obtained at 3–5 amino acid units after a hydrolysis of 30 min wit...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...

  10. Surfactant Protein A in Exhaled Endogenous Particles Is Decreased in Chronic Obstructive Pulmonary Disease (COPD Patients: A Pilot Study.

    Directory of Open Access Journals (Sweden)

    Mona Lärstad

    Full Text Available Exhaled, endogenous particles are formed from the epithelial lining fluid in small airways, where surfactant protein A (SP-A plays an important role in pulmonary host defense. Based on the knowledge that chronic obstructive pulmonary disease (COPD starts in the small airway epithelium, we hypothesized that chronic inflammation modulates peripheral exhaled particle SP-A and albumin levels. The main objective of this explorative study was to compare the SP-A and albumin contents in exhaled particles from patients with COPD and healthy subjects and to determine exhaled particle number concentrations.Patients with stable COPD ranging from moderate to very severe (n = 13, and healthy non-smoking subjects (n = 12 were studied. Subjects performed repeated breath maneuvers allowing for airway closure and re-opening, and exhaled particles were optically counted and collected on a membrane using the novel PExA® instrument setup. Immunoassays were used to quantify SP-A and albumin.COPD patients exhibited significantly lower SP-A mass content of the exhaled particles (2.7 vs. 3.9 weight percent, p = 0.036 and lower particle number concentration (p<0.0001 than healthy subjects. Albumin mass contents were similar for both groups.Decreased levels of SP-A may lead to impaired host defense functions of surfactant in the airways, contributing to increased susceptibility to COPD exacerbations. SP-A in exhaled particles from small airways may represent a promising non-invasive biomarker of disease in COPD patients.

  11. The significance of surfactant protein gene polymorphisms in multifactorial infantile pulmonary diseases

    OpenAIRE

    Rova, M.

    2005-01-01

    Abstract Pulmonary surfactant is a lipid-protein mixture that lines the inner surface of the lung. The main function of surfactant is to reduce surface tension at the air-liquid interface, thus preventing alveolar collapse at the end of expiration. Lack of surfactant is the main cause of respiratory distress syndrome (RDS) in preterm infants. Very preterm babies are at risk of developing a lung disease called bronchopulmonary dysplasia (BPD). The surfactant proteins SP-A, -B, -C and -D ha...

  12. Congenital surfactant protein B deficiency - emphasis on imaging

    Energy Technology Data Exchange (ETDEWEB)

    Newman, B. [Dept. of Radiology, Children' s Hospital of Pittsburgh, PA (United States); Kuhn, J.P. [Dept. of Radiology, Buffalo Children' s Hospital, Buffalo, NY (United States); Kramer, S.S. [Dept. of Radiology, Children' s Hospital of Philadelphia, PA (United States); Carcillo, J.A. [Dept. of Pediatrics, Children' s Hospital of Pittsburgh, Pittsburgh, PA (United States)

    2001-05-01

    Background and objectives. Surfactant protein B deficiency has become increasingly recognized as a cause of severe prolonged respiratory distress. Little has been written about the imaging appearance and the role of imaging in diagnosis. Materials and methods. Three newborn infants with severe respiratory distress exhibited prolonged diffuse pulmonary opacification radiographically. Results. Diffuse ground-glass opacity and markedly prominent interlobular septa suggesting alveolar proteinosis were present on early thin-section chest computed tomographic (CT) images. Fibrotic changes with prominent interlobular septal thickening were present on a later CT. Surfactant protein B deficiency was confirmed by alveolar lavage and peripheral blood DNA analysis. Conclusion. Thin-section chest CT imaging contributes important information when this diagnosis is considered. (orig.)

  13. Congenital surfactant protein B deficiency - emphasis on imaging

    International Nuclear Information System (INIS)

    Background and objectives. Surfactant protein B deficiency has become increasingly recognized as a cause of severe prolonged respiratory distress. Little has been written about the imaging appearance and the role of imaging in diagnosis. Materials and methods. Three newborn infants with severe respiratory distress exhibited prolonged diffuse pulmonary opacification radiographically. Results. Diffuse ground-glass opacity and markedly prominent interlobular septa suggesting alveolar proteinosis were present on early thin-section chest computed tomographic (CT) images. Fibrotic changes with prominent interlobular septal thickening were present on a later CT. Surfactant protein B deficiency was confirmed by alveolar lavage and peripheral blood DNA analysis. Conclusion. Thin-section chest CT imaging contributes important information when this diagnosis is considered. (orig.)

  14. Is treatment with hydroxychloroquine effective in surfactant protein C deficiency?

    Science.gov (United States)

    Rabach, Ingrid; Poli, Furio; Zennaro, Floriana; Germani, Claudio; Ventura, Alessandro; Barbi, Egidio

    2013-05-01

    We present the case of two twin brothers with surfactant protein C deficiency who were treated with hydroxychloroquine for three years, with apparent success. The exact physiopathology of this disease is not known and there is no specific treatment for it. There is merely news from a few previous descriptions in the literature about the use of hydroxychloroquine for surfactant protein C deficiency with satisfactory results. Two years after the treatment was withdrawn, the twins were evaluated once again: they presented no new infections, growth and general state were normal and chest CT showed a notable additional reduction in the interstitial pneumopathy. These data seem to cast some doubt on the efficacy of hydroxychloroquine, and they suggest that the clinical improvement was simply the natural evolution of the disease. PMID:23137777

  15. Glucocorticoid regulation of human pulmonary surfactant protein-B (SP-B) mRNA stability is independent of activated glucocorticoid receptor

    OpenAIRE

    Tillis, Ceá C.; Huang, Helen W.; Bi, Weizhen; Pan, Su; Bruce, Shirley R.; Alcorn, Joseph L.

    2011-01-01

    Adequate expression of surfactant protein-B (SP-B) is critical in the function of pulmonary surfactant to reduce alveolar surface tension. Expression of SP-B mRNA is restricted to specific lung-airway epithelial cells, and human SP-B mRNA stability is increased in the presence of the synthetic glucocorticoid dexamethasone (DEX). Although the mechanism of SP-B mRNA stabilization by DEX is unknown, studies suggest involvement of the glucocorticoid receptor (GR). We developed a dual-cistronic pl...

  16. Surfactant synthesis, secretion, and function in alveoli and small airways. Review of the physiologic basis for pharmacologic intervention.

    Science.gov (United States)

    Mason, R J

    1987-01-01

    Surface-active material is known to lower surface tension at the air/liquid interface and provide alveolar stability. Less well appreciated is the potential role of surface-active material in maintaining the patency of small airways and in transporting particles from the alveolar surface to the small airways. The interactions between the two dominant secretory cells in the terminal lung units, i.e., the alveolar type II cell and the Clara cell, are just starting to be discovered. The biochemical signals for secretion of surface-active material in vivo are still not known. The dominant physiologic stimulus is hyperventilation. Secretion in vitro is stimulated by activation of protein-kinase C (tetradecanoyl phorbol acetate), protein-kinase A (cyclic AMP, beta-adrenergic agonists, cholera toxin), and calcium ionophores (A23187 or ionomycin). The biochemical basis for secretion will be discussed. PMID:2885907

  17. The Diverse Structures and Functions of Surfactant Proteins.

    Science.gov (United States)

    Schor, Marieke; Reid, Jack L; MacPhee, Cait E; Stanley-Wall, Nicola R

    2016-07-01

    Surface tension at liquid-air interfaces is a major barrier that needs to be surmounted by a wide range of organisms; surfactant and interfacially active proteins have evolved for this purpose. Although these proteins are essential for a variety of biological processes, our understanding of how they elicit their function has been limited. However, with the recent determination of high-resolution 3D structures of several examples, we have gained insight into the distinct shapes and mechanisms that have evolved to confer interfacial activity. It is now a matter of harnessing this information, and these systems, for biotechnological purposes. PMID:27242193

  18. Pulmonary surfactant protein A (SP-A) specifically binds dipalmitoylphosphatidylcholine

    International Nuclear Information System (INIS)

    Phospholipids are the major components of pulmonary surfactant. Dipalmitoylphosphatidylcholine is believed to be especially essential for the surfactant function of reducing the surface tension at the air-liquid interface. Surfactant protein A (SP-A) with a reduced denatured molecular mass of 26-38 kDa, characterized by a collagen-like structure and N-linked glycosylation, interacts strongly with a mixture of surfactant-like phospholipids. In the present study the direct binding of SP-A to phospholipids on a thin layer chromatogram was visualized using 125I-SP-A as a probe, so that the phospholipid specificities of SP-A binding and the structural requirements of SP-A and phospholipids for the binding could be examined. Although 125I-SP-A bound phosphatidylcholine and sphingomyeline, it was especially strong in binding dipalmitoylphosphatidylcholine, but failed to bind phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, and phosphatidylserine. Labeled SP-A also exhibited strong binding to distearoylphosphatidylcholine, but weak binding to dimyristoyl-, 1-palmitoyl-2-linoleoyl-, and dilinoleoylphosphatidylcholine. Unlabeled SP-A readily competed with labeled SP-A for phospholipid binding. SP-A strongly bound dipalmitoylglycerol produced by phospholipase C treatment of dipalmitoylphosphatidylcholine, but not palmitic acid. This protein also failed to bind lysophosphatidylcholine produced by phospholipase A2 treatment of dipalmitoylphosphatidylcholine. 125I-SP-A shows almost no binding to dipalmitoylphosphatidylglycerol and dipalmitoylphosphatidylethanolamine. The addition of 10 mM EGTA into the binding buffer reduced much of the 125I-SP-A binding to phospholipids. Excess deglycosylated SP-A competed with labeled SP-A for binding to dipalmitoylphosphatidylcholine, but the excess collagenase-resistant fragment of SP-A failed

  19. Modifications in structure and interaction of nanoparticle-protein-surfactant complexes in electrolyte solution

    Science.gov (United States)

    Mehan, Sumit; Kumar, S.; Aswal, V. K.; Schweins, R.

    2016-05-01

    SANS experiments of three-component system of anionic silica nanoparticles, anionic BSA protein and anionic SDS surfactants have been carried out without and with electrolyte in aqueous solution. In both the cases, the interaction of surfactant with protein results in formation of bead-necklace structure of protein-surfactant complexes in solution. These protein-surfactant complexes interact very differently with nanoparticles in absence and presence of electrolyte. In absence of electrolyte, nanoparticles remain in dispersed phase in solution, whereas with the addition of electrolyte the nanoparticles fractal aggregates are formed. SANS describes the phase behavior to be governed by competition of electrostatic and depletion interactions among the components solution.

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

    Directory of Open Access Journals (Sweden)

    Russo Scott J

    2005-08-01

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

  1. Staphylococcus aureus and Pseudomonas aeruginosa express and secrete human surfactant proteins.

    Directory of Open Access Journals (Sweden)

    Lars Bräuer

    Full Text Available Surfactant proteins (SP, originally known from human lung surfactant, are essential to proper respiratory function in that they lower the surface tension of the alveoli. They are also important components of the innate immune system. The functional significance of these proteins is currently reflected by a very large and growing number of publications. The objective goal of this study was to elucidate whether Staphylococcus aureus and Pseudomonas aeruginosa is able to express surfactant proteins. 10 different strains of S. aureus and P. aeruginosa were analyzed by means of RT-PCR, Western blot analysis, ELISA, immunofluorescence microscopy and immunoelectron microscopy. The unexpected and surprising finding revealed in this study is that different strains of S. aureus and P. aeruginosa express and secrete proteins that react with currently commercially available antibodies to known human surfactant proteins. Our results strongly suggest that the bacteria are either able to express 'human-like' surfactant proteins on their own or that commercially available primers and antibodies to human surfactant proteins detect identical bacterial proteins and genes. The results may reflect the existence of a new group of bacterial surfactant proteins and DNA currently lacking in the relevant sequence and structure databases. At any rate, our knowledge of human surfactant proteins obtained from immunological and molecular biological studies may have been falsified by the presence of bacterial proteins and DNA and therefore requires critical reassessment.

  2. Staphylococcus aureus and Pseudomonas aeruginosa express and secrete human surfactant proteins.

    Science.gov (United States)

    Bräuer, Lars; Schicht, Martin; Worlitzsch, Dieter; Bensel, Tobias; Sawers, R Gary; Paulsen, Friedrich

    2013-01-01

    Surfactant proteins (SP), originally known from human lung surfactant, are essential to proper respiratory function in that they lower the surface tension of the alveoli. They are also important components of the innate immune system. The functional significance of these proteins is currently reflected by a very large and growing number of publications. The objective goal of this study was to elucidate whether Staphylococcus aureus and Pseudomonas aeruginosa is able to express surfactant proteins. 10 different strains of S. aureus and P. aeruginosa were analyzed by means of RT-PCR, Western blot analysis, ELISA, immunofluorescence microscopy and immunoelectron microscopy. The unexpected and surprising finding revealed in this study is that different strains of S. aureus and P. aeruginosa express and secrete proteins that react with currently commercially available antibodies to known human surfactant proteins. Our results strongly suggest that the bacteria are either able to express 'human-like' surfactant proteins on their own or that commercially available primers and antibodies to human surfactant proteins detect identical bacterial proteins and genes. The results may reflect the existence of a new group of bacterial surfactant proteins and DNA currently lacking in the relevant sequence and structure databases. At any rate, our knowledge of human surfactant proteins obtained from immunological and molecular biological studies may have been falsified by the presence of bacterial proteins and DNA and therefore requires critical reassessment. PMID:23349731

  3. Observation of two different fractal structures in nanoparticle, protein and surfactant complexes

    Energy Technology Data Exchange (ETDEWEB)

    Mehan, Sumit, E-mail: sumit.mehan@gmail.com; Kumar, Sugam, E-mail: sumit.mehan@gmail.com; Aswal, V. K., E-mail: sumit.mehan@gmail.com [Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai-400085 (India)

    2014-04-24

    Small angle neutron scattering has been carried out from a complex of nanoparticle, protein and surfactant. Although all the components are similarly (anionic) charged, we have observed strong interactions in their complex formation. It is characterized by the coexistence of two different mass fractal structures. The first fractal structure is originated from the protein and surfactant interaction and second from the depletion effect of first fractal structure leading the nanoparticle aggregation. The fractal structure of protein-surfactant complex represents to bead necklace structure of micelle-like clusters of surfactant formed along the unfolded protein chain. Its fractal dimension depends on the surfactant to protein ratio (r) and decreases with the increase in r. However, fractal dimension of nanoparticle aggregates in nanoparticle-protein complex is found to be independent of protein concentration and governed by the diffusion limited aggregation like morphology.

  4. Observation of two different fractal structures in nanoparticle, protein and surfactant complexes

    Science.gov (United States)

    Mehan, Sumit; Kumar, Sugam; Aswal, V. K.

    2014-04-01

    Small angle neutron scattering has been carried out from a complex of nanoparticle, protein and surfactant. Although all the components are similarly (anionic) charged, we have observed strong interactions in their complex formation. It is characterized by the coexistence of two different mass fractal structures. The first fractal structure is originated from the protein and surfactant interaction and second from the depletion effect of first fractal structure leading the nanoparticle aggregation. The fractal structure of protein-surfactant complex represents to bead necklace structure of micelle-like clusters of surfactant formed along the unfolded protein chain. Its fractal dimension depends on the surfactant to protein ratio (r) and decreases with the increase in r. However, fractal dimension of nanoparticle aggregates in nanoparticle-protein complex is found to be independent of protein concentration and governed by the diffusion limited aggregation like morphology.

  5. Staphylococcus aureus and Pseudomonas aeruginosa Express and Secrete Human Surfactant Proteins

    OpenAIRE

    Bräuer, Lars; Schicht, Martin; Worlitzsch, Dieter; Bensel, Tobias; Sawers, R. Gary; Paulsen, Friedrich

    2013-01-01

    Surfactant proteins (SP), originally known from human lung surfactant, are essential to proper respiratory function in that they lower the surface tension of the alveoli. They are also important components of the innate immune system. The functional significance of these proteins is currently reflected by a very large and growing number of publications. The objective goal of this study was to elucidate whether Staphylococcus aureus and Pseudomonas aeruginosa is able to express surfactant prot...

  6. Spatial and temporal expression of surfactant proteins in hyperoxia-induced neonatal rat lung injury

    OpenAIRE

    Walther Frans J; Sengupta Sujata; Fijlstra Margot; ter Horst Simone AJ; Wagenaar Gerry TM

    2006-01-01

    Abstract Background Bronchopulmonary dysplasia, a complex chronic lung disease in premature children in which oxidative stress and surfactant deficiency play a crucial role, is characterized by arrested alveolar and vascular development of the immature lung. The spatial and temporal patterns of expression of surfactant proteins are not yet fully established in newborn infants and animal models suffering from BPD. Methods We studied the mRNA expression of surfactant proteins (SP) A, -B, -C and...

  7. Effect of exogenous surfactant therapy on levels of pulmonary surfactant proteins A and D in preterm infants with respiratory distress syndrome

    OpenAIRE

    Bae, Young Min; Bae, Chong-Woo; Oh, Myung Ho; Lee, Sang Han; Woo, Kee Min; Jung, Keum Bun

    2009-01-01

    Objectives: To examine whether exogenous pulmonary surfactants (exPS) substitute for or merely supplement endogenous pulmonary surfactants (enPS) by looking at sequential changes in the surfactant proteins (SP) SP-A and SP-D in alveolar pools. Methods: Fourteen preterm infants with RDS treated with an artificial surfactant were compared to five normal-term infants without RDS who were treated with artificial ventilation at birth. Results: Immediately after birth, SP-A and SP-D were essentia...

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

    DEFF Research Database (Denmark)

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

    1991-01-01

    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....... Crude extracts from isolated EO granules also stimulated RGC release, suggesting that a granular protein might be responsible. Three proteins derived from EO granules, EO-derived neurotoxin, EO cationic protein (ECP), and major basic protein (MBP) were separated by sequential sizing and affinity...... 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...

  9. Detection of surfactant protein A (SP-A) and surfactant protein D (SP-D) in equine synovial fluid with immunoblotting

    OpenAIRE

    Kankavi, Orhan; Michael S. Roberts

    2004-01-01

    Once considered unique to the lung, surfactant proteins have been clearly identified in the intestine and peritoneum and are suggested to exist in several other organs. In the lung, surfactant proteins assist in the formation of a monolayer of surface-active phospholipid at the liquid–air interface of the alveolar lining, reducing the surface tension at this surface. In contrast, surface-active phospholipid adsorbed to articular surfaces has been identified as the load-bearing boundary lubric...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  11. STRUCTURE, FUNCTION AND DEFICIENCY DISEASES OF LUNG SURFACTANT PROTEIN-C

    OpenAIRE

    2014-01-01

    Pulmonary surfactant is a mixture of lipids and hydrophobic surfactant proteins B (SP-B) and SP-C and hydrophilic proteins SP-A and SP-D. Pulmonary surfactant reduces the surface tension at the air-water interface of the lung alveoli by forming a surface active film. In this way, it prevents alveoli from collapsing and facilitates the process of breathing. SP-C cooperates with SP-B to enhance the surface active properties of surfactant phospholipids. Reports on the association of lung disease...

  12. Regulation of surfactant protein D in the rodent prostate

    Directory of Open Access Journals (Sweden)

    Maldonado Cristina A

    2007-11-01

    Full Text Available Abstract Background Surfactant protein D (SP-D is an innate immune protein that is present in mucosal lined surfaces throughout the human body, including the male reproductive tract. In the present study, we characterized the regulation of SP-D expression in the mouse and rat prostate. Methods Real time reverse transcriptase polymerase chain reaction (RT-PCR and immunostaining were used to characterize SP-D mRNA and protein in the mouse male reproductive tract. In order to evaluate the effects of testosterone on SP-D gene expression, we measured SP-D mRNA levels via real time RT-PCR in prostates from sham-castrated mice and castrated mice. In addition, we used a rat prostatitis model in which Escherichia coli was injected into the prostate in vivo to determine if infection influences SP-D protein levels in the prostate. Results We found that SP-D mRNA and protein are present throughout the mouse male reproductive tract, including in the prostate. We determined that castration increases prostate SP-D mRNA levels (~7 fold when compared to levels in sham-castrated animals. Finally, we demonstrated that infection in the prostate results in a significant increase in SP-D content 24 and 48 hours post-infection. Conclusion Our results suggest that infection and androgens regulate SP-D in the prostate.

  13. Surfactant protein A integrates activation signal strength to differentially modulate T cell proliferation.

    Science.gov (United States)

    Mukherjee, Sambuddho; Giamberardino, Charles; Thomas, Joseph; Evans, Kathy; Goto, Hisatsugu; Ledford, Julie G; Hsia, Bethany; Pastva, Amy M; Wright, Jo Rae

    2012-02-01

    Pulmonary surfactant lipoproteins lower the surface tension at the alveolar-airway interface of the lung and participate in host defense. Previous studies reported that surfactant protein A (SP-A) inhibits lymphocyte proliferation. We hypothesized that SP-A-mediated modulation of T cell activation depends upon the strength, duration, and type of lymphocyte activating signals. Modulation of T cell signal strength imparted by different activating agents ex vivo and in vivo in different mouse models and in vitro with human T cells shows a strong correlation between strength of signal (SoS) and functional effects of SP-A interactions. T cell proliferation is enhanced in the presence of SP-A at low SoS imparted by exogenous mitogens, specific Abs, APCs, or in homeostatic proliferation. Proliferation is inhibited at higher SoS imparted by different doses of the same T cell mitogens or indirect stimuli such as LPS. Importantly, reconstitution with exogenous SP-A into the lungs of SP-A(-/-) mice stimulated with a strong signal also resulted in suppression of T cell proliferation while elevating baseline proliferation in unstimulated T cells. These signal strength and SP-A-dependent effects are mediated by changes in intracellular Ca(2+) levels over time, involving extrinsic Ca(2+)-activated channels late during activation. These effects are intrinsic to the global T cell population and are manifested in vivo in naive as well as memory phenotype T cells. Thus, SP-A appears to integrate signal thresholds to control T cell proliferation. PMID:22219327

  14. 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; Nordestgaard, Børge G

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    The collectin surfactant protein D (SP-D) is an important component of the pulmonary innate immune system, but SP-D is also present on extrapulmonary epithelial surfaces and in serum, where it has been used as a biomarker for pulmonary disease states. In this study, we investigate the mechanisms...... intraclass correlation was significantly higher for monozygotic (MZ) twin pairs than for dizygotic (DZ) twin pairs. Serum SP-D variance was influenced by nonshared environmental effects and additive genetic effects. Multivariate analysis of MZ and DZ covariance matrixes showed significant genetic correlation...... among serum SP-D and metabolic variables. The Met11Thr variant explained a significant part of the heritability indicating that serum SP-D variance could be decomposed into non-shared environmental effects (e(2) = 0.19), additive genetic effects (h(2) = 0.42), and the effect of the Met11Thr variations...

  16. The surfactant protein C mutation A116D alters cellular processing, stress tolerance, surfactant lipid composition, and immune cell activation

    OpenAIRE

    Zarbock Ralf; Woischnik Markus; Sparr Christiane; Thurm Tobias; Kern Sunčana; Kaltenborn Eva; Hector Andreas; Hartl Dominik; Liebisch Gerhard; Schmitz Gerd; Griese Matthias

    2012-01-01

    Abstract Background Surfactant protein C (SP-C) is important for the function of pulmonary surfactant. Heterozygous mutations in SFTPC, the gene encoding SP-C, cause sporadic and familial interstitial lung disease (ILD) in children and adults. Mutations mapping to the BRICHOS domain located within the SP-C proprotein result in perinuclear aggregation of the proprotein. In this study, we investigated the effects of the mutation A116D in the BRICHOS domain of SP-C on cellular homeostasis. We al...

  17. Nucleotide and amino acid sequences of pulmonary surfactant protein SP 18 and evidence for cooperation between SP 18 and SP 28-36 in surfactant lipid adsorption.

    OpenAIRE

    Hawgood, S; Benson, B J; Schilling, J; Damm, D; Clements, J. A.; White, R T

    1987-01-01

    Pulmonary surfactant is a lipid-rich material that promotes alveolar stability by lowering the surface tension at the air-fluid interface in the peripheral air spaces. The turnover of surfactant phospholipids in the alveolar space is fast, and several lines of evidence suggest there is rapid formation and replenishment of the phospholipid surface film during normal respiration. Specific proteins may regulate these dynamic surface properties. The predominant surfactant protein is a well-charac...

  18. Macrophage dysfunction and susceptibility to pulmonary Pseudomonas aeruginosa infection in surfactant protein C-deficient mice.

    Science.gov (United States)

    Glasser, Stephan W; Senft, Albert P; Whitsett, Jeffrey A; Maxfield, Melissa D; Ross, Gary F; Richardson, Theresa R; Prows, Daniel R; Xu, Yan; Korfhagen, Thomas R

    2008-07-01

    To determine the role of surfactant protein C (SP-C) in host defense, SP-C-deficient (Sftpc-/-) mice were infected with the pulmonary pathogen Pseudomonas aeruginosa by intratracheal injection. Survival of young, postnatal day 14 Sftpc-/- mice was decreased in comparison to Sftpc+/+ mice. The sensitivity to Pseudomonas bacteria was specific to the 129S6 strain of Sftpc-/- mice, a strain that spontaneously develops interstitial lung disease-like lung pathology with age. Pulmonary bacterial load and leukocyte infiltration were increased in the lungs of Sftpc-/- mice 24 h after infection. Early influx of polymorphonuclear leukocytes in the lungs of uninfected newborn Sftpc-/- mice relative to Sftpc+/+ mice indicate that the lack of SP-C promotes proinflammatory responses in the lung. Mucin expression, as indicated by Alcian blue staining, was increased in the airways of Sftpc-/- mice following infection. Phagocytic activity of alveolar macrophages from Sftpc-/- mice was reduced. The uptake of fluorescent beads in vitro and the number of bacteria phagocytosed by alveolar macrophages in vivo was decreased in the Sftpc-/- mice. Alveolar macrophages from Sftpc-/- mice expressed markers of alternative activation that are associated with diminished pathogen response and advancing pulmonary fibrosis. These findings implicate SP-C as a modifier of alveolar homeostasis. SP-C plays an important role in innate host defense of the lung, enhancing macrophage-mediated Pseudomonas phagocytosis, clearance and limiting pulmonary inflammatory responses. PMID:18566429

  19. Glucocorticoid Regulation of Human Pulmonary Surfactant Protein-B mRNA Stability Involves the 3′-Untranslated Region

    OpenAIRE

    Huang, Helen W.; Bi, Weizhen; Jenkins, Gaye N.; Alcorn, Joseph L.

    2007-01-01

    Expression of pulmonary surfactant, a complex mixture of lipids and proteins that acts to reduce alveolar surface tension, is developmentally regulated and restricted to lung alveolar type II cells. The hydrophobic protein surfactant protein-B (SP-B) is essential in surfactant function, and insufficient levels of SP-B result in severe respiratory dysfunction. Glucocorticoids accelerate fetal lung maturity and surfactant synthesis both experimentally and clinically. Glucocorticoids act transcr...

  20. Low molecular weight human pulmonary surfactant protein (SP5): isolation, characterization, and cDNA and amino acid sequences.

    OpenAIRE

    Warr, R G; Hawgood, S; Buckley, D I; Crisp, T M; Schilling, J; Benson, B J; Ballard, P L; Clements, J. A.; White, R T

    1987-01-01

    Pulmonary surfactant is a lipid-protein complex that promotes alveolar stability by lowering the surface tension at the air-fluid interface in the peripheral air spaces. A group of hydrophobic surfactant-associated proteins has been shown to be essential for rapid surface film formation by surfactant phospholipids. We have purified a hydrophobic surfactant protein of approximately 5 kDa that we term SP5 from bronchopulmonary lavage fluid from a patient with alveolar proteinosis and shown that...

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

    OpenAIRE

    Korfhagen, T R; Glasser, S W; Wert, S E; Bruno, M D; Daugherty, C C; McNeish, J D; Stock, J L; Potter, S S; Whitsett, J A

    1990-01-01

    Pulmonary surfactant is produced in late gestation by developing type II epithelial cells lining the alveolar epithelium of the lung. Lack of surfactant at birth is associated with respiratory distress syndrome in premature infants. Surfactant protein C (SP-C) is a highly hydrophobic peptide isolated from pulmonary tissue that enhances the biophysical activity of surfactant phospholipids. Like surfactant phospholipid, SP-C is produced by epithelial cells in the distal respiratory epithelium, ...

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

    DEFF Research Database (Denmark)

    Andersen, Kell Kleiner; Otzen, Daniel

    2009-01-01

    Using intrinsic tryptophan fluorescence, equilibria and kinetics of unfolding of acyl coenzyme A binding protein (ACBP) have been investigated in sodium alkyl sulfate surfactants of different chain length (8-16 carbon atoms) and with different proportions of the nonionic surfactant dodecyl maltos...

  3. Surfactant Protein-D Inhibits Lung Inflammation Caused by Ventilation in Premature Newborn Lambs

    OpenAIRE

    Sato, Atsuyasu; Jeffrey A Whitsett; Scheule, Ronald K.; Ikegami, Machiko

    2010-01-01

    Rationale: Premature newborns frequently require manual ventilation for resuscitation during which lung injury occurs. Although surfactant protein (SP)-D regulates pulmonary inflammation, SP-D levels are low in the preterm lung. Commercial surfactants for treatment of respiratory distress syndrome do not contain SP-D.

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

    Science.gov (United States)

    Rausch, Felix; Schicht, Martin; Paulsen, Friedrich; Ngueya, Ivan; Bräuer, Lars; Brandt, Wolfgang

    2012-01-01

    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. PMID:23094088

  5. "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.

  6. Surfactant proteins, SP-A and SP-D, in respiratory fungal infections: their role in the inflammatory response.

    Science.gov (United States)

    Carreto-Binaghi, Laura Elena; Aliouat, El Moukhtar; Taylor, Maria Lucia

    2016-01-01

    Pulmonary surfactant is a complex fluid that comprises phospholipids and four proteins (SP-A, SP-B, SP-C, and SP-D) with different biological functions. SP-B, SP-C, and SP-D are essential for the lungs' surface tension function and for the organization, stability and metabolism of lung parenchyma. SP-A and SP-D, which are also known as pulmonary collectins, have an important function in the host's lung immune response; they act as opsonins for different pathogens via a C-terminal carbohydrate recognition domain and enhance the attachment to phagocytic cells or show their own microbicidal activity by increasing the cellular membrane permeability. Interactions between the pulmonary collectins and bacteria or viruses have been extensively studied, but this is not the same for fungal pathogens. SP-A and SP-D bind glucan and mannose residues from fungal cell wall, but there is still a lack of information on their binding to other fungal carbohydrate residues. In addition, both their relation with immune cells for the clearance of these pathogens and the role of surfactant proteins' regulation during respiratory fungal infections remain unknown. Here we highlight the relevant findings associated with SP-A and SP-D in those respiratory mycoses where the fungal infective propagules reach the lungs by the airways. PMID:27250970

  7. Binding of cationic surfactants to DNA, protein and DNA-protein mixtures.

    Science.gov (United States)

    Gani, S A; Chattoraj, D K; Mukherjee, D C

    1999-06-01

    Extent of binding (gamma 2(1)) of cationic surfactants cetyltrimethyl ammonium bromide (CTAB), myristyltrimethyl ammonium bromide (MTAB) and dodecyl trimethyl ammonium bromide (DTAB) to calf-thymus DNA, bovine serum albumin (BSA) and to their binary mixture respectively have been measured as function of bulk concentration of the surfactant by using equilibrium dialysis technique. Binding of CTAB has been studied at different pH, ionic strength (mu), temperature and biopolymer composition and with native and denatured states of the biopolymers. The chain-length of different long chain amines plays a significant role in the extent of binding under identical solution condition. The binding ratios for CTAB to collagen, gelatin, DNA-collagen and DNA-gelatin mixtures respectively have also been determined. The conformational structures of different biopolymers are observed to play significant role in macromolecular interactions between protein and DNA in the presence of CTAB. From the experimental values of the maximum binding ratio (gamma 2m) at the saturation level for each individual biopolymer, ideal values (gamma 2m)id have been theoretically calculated for binary mixtures of biopolymers using additivity rule. The protein-DNA-CTAB interaction in mixture has been explained in terms of the deviation (delta) of (gamma 2m) from (gamma 2m)id in the presence of a surfactant in bulk. The binding of surfactants to biopolymers and to their binary mixtures are compared more precisely in terms of the Gibbs' free energy decrease (-delta G degree) for the saturation of the binding sites in the biopolymers or biopolymer mixtures with the change of the bulk surfactant activity from zero to unity in the rational mole fraction scale. PMID:10650715

  8. Effects of lung surfactant proteins, SP-B and SP-C, and palmitic acid on monolayer stability.

    OpenAIRE

    Ding, J; Takamoto, D Y; von Nahmen, A; Lipp, M M; Lee, K Y; Waring, A J; Zasadzinski, J A

    2001-01-01

    Langmuir isotherms and fluorescence and atomic force microscopy images of synthetic model lung surfactants were used to determine the influence of palmitic acid and synthetic peptides based on the surfactant-specific proteins SP-B and SP-C on the morphology and function of surfactant monolayers. Lung surfactant-specific protein SP-C and peptides based on SP-C eliminate the loss to the subphase of unsaturated lipids necessary for good adsorption and respreading by inducing a transition between...

  9. Thermodynamics, interfacial pressure isotherms and dilational rheology of mixed protein-surfactant adsorption layers.

    Science.gov (United States)

    Fainerman, V B; Aksenenko, E V; Krägel, J; Miller, R

    2016-07-01

    Proteins and their mixtures with surfactants are widely used in many applications. The knowledge of their solution bulk behavior and its impact on the properties of interfacial layers made great progress in the recent years. Different mechanisms apply to the formation process of protein/surfactant complexes for ionic and non-ionic surfactants, which are governed mainly by electrostatic and hydrophobic interactions. The surface activity of these complexes is often remarkably different from that of the individual protein and has to be considered in respective theoretical models. At very low protein concentration, small amounts of added surfactants can change the surface activity of proteins remarkably, even though no strongly interfacial active complexes are observed. Also small added amounts of non-ionic surfactants change the surface activity of proteins in the range of small bulk concentrations or surface coverages. The modeling of the equilibrium adsorption behavior of proteins and their mixtures with surfactants has reached a rather high level. These models are suitable also to describe the high frequency limits of the dilational viscoelasticity of the interfacial layers. Depending on the nature of the protein/surfactant interactions and the changes in the interfacial layer composition rather complex dilational viscoelasticities can be observed and described by the available models. The differences in the interfacial behavior, often observed in literature for studies using different experimental methods, are at least partially explained by a depletion of proteins, surfactants and their complexes in the range of low concentrations. A correction of these depletion effects typically provides good agreement between the data obtained with different methods, such as drop and bubble profile tensiometry. PMID:26198014

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

    OpenAIRE

    Habauka M. Kwaambwa; Raymond Maikokera

    2009-01-01

    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, an...

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    recombinant SP-C variants so obtained retained more than 50% alpha-helical content and showed surface activity comparable to the native protein, as measured by surface spreading of lipid/protein suspensions and from compression pi-A isotherms of lipid/protein films. Compared to the protein purified from......Surfactant protein C (SP-C) is an essential component for the surface tension-lowering activity of the pulmonary surfactant system. It contains a valine-rich alpha helix that spans the lipid bilayer, and is one of the most hydrophobic proteins known so far. SP-C is also an essential component of...

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  13. Human Surfactant Protein – A Gene Locus for Genetic Studies in the Finnish Population

    OpenAIRE

    Mika Rämet; Ritva Haataja; Riitta Marttila; Anu-Maaria Häamäaläainen; Mikael Knip; Mikko Hallman

    2000-01-01

    Lung surfactant lowers the surface tension but surfactant proteins also have other functions. Surfactant protein A (SP-A) has a well-defined role in innate immunity. The gene locus for human SP-A genes is in chromosome 10q21 through q24 and consists of two highly homologous functional SP-A genes (SP-A1 and SP-A2) and a pseudogene. Several alleles that differ by a single amino acid have been identified for both SP-A genes. The SP-A gene locus has been shown to be sufficiently polymorphic for g...

  14. Glucocorticoids both stimulate and inhibit production of pulmonary surfactant protein A in fetal human lung.

    OpenAIRE

    Liley, H G; White, R T; Benson, B J; Ballard, P L

    1988-01-01

    Pulmonary surfactant is a mixture of phospholipids and proteins which stabilizes lung alveoli and prevents respiratory failure. The surfactant-associated protein of Mr = 28,000-36,000 (SP-A) influences the structure, function (film formation), and metabolism of surfactant. We have characterized glucocorticoid regulation of SP-A and SP-A mRNA in explants of fetal human lung. The time course of response to dexamethasone was biphasic, with early stimulation and later inhibition of SP-A accumulat...

  15. Increased and Prolonged Pulmonary Fibrosis in Surfactant Protein C-Deficient Mice Following Intratracheal Bleomycin

    OpenAIRE

    Lawson, William E.; Polosukhin, Vasiliy V.; Stathopoulos, Georgios T.; Zoia, Ornella; Han, Wei; Kirk B. Lane; Li, Bo; Donnelly, Edwin F.; Holburn, George E.; Lewis, Kenneth G.; Collins, Robert D.; Hull, William M.; Glasser, Stephan W.; Jeffrey A Whitsett; Blackwell, Timothy S.

    2005-01-01

    Recent reports have linked mutations in the surfactant protein C gene (SFTPC) to familial forms of pulmonary fibrosis, but it is uncertain whether deficiency of mature SP-C contributes to disease pathogenesis. In this study, we evaluated bleomycin-induced lung fibrosis in mice with genetic deletion of SFTPC. Compared with wild-type (SFTPC+/+) controls, mice lacking surfactant protein C (SFTPC−/−) had greater lung neutrophil influx at 1 week after intratracheal bleomycin, greater weight loss d...

  16. Pulmonary surfactant proteins B and C : molecular organisation and involvement in respiratory disease

    OpenAIRE

    Zaltash, Shahparak

    2000-01-01

    Lung surfactant is a complex mixture of phospholipids and proteins with the main function to reduce the surface tension at the alveolar air/liquid interface. Surfactant protein B (SP-B) and C (SP-C) are hydrophobic but unrelated in structure, and probably have unique functional roles in the formation of the surface-active monolayer. SP-B deficiency causes lethal respiratory failure, but SP-C null mice show no respiratory dysfunction. This thesis is focused on the molecular ...

  17. Lipid Specificity of Surfactant Protein B Studied by Time-of-Flight Secondary Ion Mass Spectrometry

    OpenAIRE

    Breitenstein, D. (Daniel); Batenburg, J.J.; Hagenhoff, B.; Galla, H.-J.

    2006-01-01

    One of the key functions of mammalian pulmonary surfactant is the reduction of surface tension to minimal values. To fulfill this function it is expected to become enriched in dipalmitoylphosphatidylcholine either on its way from the alveolar type II pneumocytes to the air/water interface of the lung or within the surface film during compression and expansion of the alveoli during the breathing cycle. One protein that may play a major role in this enrichment process is the surfactant protein ...

  18. The surfactant system protects both fetus and newborn.

    Science.gov (United States)

    Hallman, Mikko

    2013-01-01

    Surfactant complex and its individual components decrease surface tension, silence inflammatory responses, bind and destroy air-borne microbes, facilitate phagocytosis by alveolar macrophages and bind endogenous and exogenous molecules. Surfactant components generally decrease harmful inflammatory responses. New exogenous surfactants and new indications for surfactant therapy remain to be studied. At term the pool of human surfactant from developing airways extends to the amniotic cavity and to the gastrointestinal tract. Preterm labor-inducing inflammatory ligands (interleukin-1 or lipopolysaccharide) cause a robust induction of surfactant complex and lower the risk of respiratory distress syndrome (RDS). The effect of antenatal glucocorticoid therapy is complementary. According to transgenic experiments or genetic evidence in humans, surfactant proteins A, D or C (SP-A, SP-D, SP-C), expressed in fetal tissue, influence the onset of term or preterm labor. After birth, the surface tension-reducing and the inflammation-silencing effects of exogenous and endogenous surfactant are complementary. Surfactant proteins influence the genetic predisposition of RDS, bronchopulmonary dysplasia (BPD) and airway infections in early infancy. Moderate to severe BPD has a strong genetic predisposition. Deleterious mutations of SP-B, ABCA3 or SP-C cause congenital interstitial lung disease that mimics the phenotype of established severe BPD. I propose that lung surfactant protects both the fetus and the newborn. Surfactant ameliorates inflammatory responses that are harmful to the mother, fetus and infant. In chorioamnionitis, inflammatory ligands are carried from the fetal membranes to the alveolar space via amniotic fluid and developing airways. They induce surfactant synthesis and secretion. Surfactant ameliorates severe inflammatory responses in fetal compartments and promotes spontaneous preterm birth. PMID:23736009

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

    Science.gov (United States)

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

    2016-03-01

    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. PMID:26389817

  20. Biomarkers in Airway Diseases

    Directory of Open Access Journals (Sweden)

    Janice M Leung

    2013-01-01

    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.

  1. Overcoming inactivation of the lung surfactant by serum proteins: a potential role for fluorocarbons?

    Science.gov (United States)

    Krafft, Marie Pierre

    2015-08-14

    In many pulmonary conditions serum proteins interfere with the normal adsorption of components of the lung surfactant to the surface of the alveoli, resulting in lung surfactant inactivation, with potentially serious untoward consequences. Here, we review the strategies that have recently been designed in order to counteract the biophysical mechanisms of inactivation of the surfactant. One approach includes protein analogues or peptides that mimic the native proteins responsible for innate resistance to inactivation. Another perspective uses water-soluble additives, such as electrolytes and hydrophilic polymers that are prone to enhance adsorption of phospholipids. An alternative, more recent approach consists of using fluorocarbons, that is, highly hydrophobic inert compounds that were investigated for partial liquid ventilation, that modify interfacial properties and can act as carriers of exogenous lung surfactant. The latter approach that allows fluidisation of phospholipid monolayers while maintaining capacity to reach near-zero surface tension definitely warrants further investigation. PMID:26110877

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

    DEFF Research Database (Denmark)

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

    2001-01-01

    agglutinin bound in a similar way to Streptococcus mutans and surfactant protein-D. Histochemically, the distribution of gp-340 in the submandibular salivary glands was identical with the agglutinin distribution, as shown in a previous paper [Takano, Bogert, Malamud, Lally and Hand (1991) Anat. Rec. 230, 307......-318]. We conclude that agglutinin is identical with gp-340, and that this molecule interacts with S. mutans and surfactant protein-D....

  3. Intelectin is required for IL-13-induced monocyte chemotactic protein-1 and -3 expression in lung epithelial cells and promotes allergic airway inflammation

    OpenAIRE

    Gu, Naibing; Kang, Guannan; Jin, Chang'E; Xu, Yongjian; ZHANG, ZHENXIANG; Erle, David J.; Zhen, Guohua

    2009-01-01

    Asthma is characterized by airway inflammation, mucus overproduction, airway hyperreactivity, and peribronchial fibrosis. Intelectin has been shown to be increased in airway epithelium of asthmatics. However, the role of intelectin in the pathogenesis of asthma is unknown. Airway epithelial cells can secrete chemokines such as monocyte chemotactic protein (MCP)-1 and -3 that play crucial roles in asthmatic airway inflammation. We hypothesized that intelectin plays a role in allergic airway in...

  4. Assessment of Surfactant Protein A (SP-A dependent agglutination

    Directory of Open Access Journals (Sweden)

    Griese Matthias

    2010-11-01

    Full Text Available Abstract Background Monomers of the collectin surfactant associated protein-A (SP-A are arranged in trimers and higher oligomers. The state of oligomerization differs between individuals and likely affects SP-A's functional properties. SP-A can form aggregates together with other SP-A molecules. Here we report and assess a test system for the aggregate forming properties of SP-A in serum and broncho-alveolar lavage samples. Methods Anti-SP-A antibodies fixed to latex beads bound SP-A at its N-terminal end and allowed the interaction with other SP-A molecules in a given sample by their C-terminal carbohydrate recognition domain (CRD to agglutinate the beads to aggregates, which were quantified by light microscopy. Results SP-A aggregation was dependent on its concentration, the presence of calcium, and was dose-dependently inhibited by mannose. Unaffected by the presence of SP-D no aggregation was observed in absence of SP-A. The more complex the oligomeric structure of SP-A present in a particular sample, the better was its capability to induce aggregation at a given total concentration of SP-A. SP-A in serum agglutinated independently of the pulmonary disease; in contrast SP-A in lung lavage fluid was clearly inferior in patients with chronic bronchitis and particularly with cystic fibrosis compared to controls. Conclusions The functional status of SP-A with respect to its aggregating properties in serum and lavage samples can be easily assessed. SP-A in lung lavage fluid in patients with severe neutrophilic bronchitis was inferior.

  5. Surface activity of pulmonary surfactant protein B : from biophysical properties to clinical application

    OpenAIRE

    Diemel, Robert Victor

    2002-01-01

    The global aim of our studies was to obtain more information about the mechanisms involved in the action of the hydrophobic surfactant components, with a special attention for SP-B. To reach this goal, many different assays and devices were used, including a pressure driven captive bubble surfactometer (CBS), a spreading trough and an atomic force microscope. The thesis starts with a general overview about the function and structural variation of the surfactant proteins (chapter 1). It is des...

  6. Circadian Rhythm of Surfactant Protein A, B and C mRNA in Rats

    OpenAIRE

    Kim, Chung Mi; Sohn, Jang Won; Yoon, Ho Joo; Shin, Dong Ho; Park, Sung Soo

    2003-01-01

    Background: All organisms have developed an internal timing system capable of reacting to and anticipating environmental stimuli with a program of appropriately timed metabolic, physiologic and behavioral events. The alveolar epithelial type II cell of the mammalian lung synthesizes, stores, and secretes a lipoprotein pulmonary surfactant, which functions to stabilize alveoli at low lung volumes. Methods: The authors investigated the diurnal variation of surfactant protein A, B and C mRNA acc...

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

    Directory of Open Access Journals (Sweden)

    Raymond Maikokera

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Daniela eSalgado

    2014-12-01

    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.

  9. Human Pulmonary Surfactant Protein SP-A1 Provides Maximal Efficiency of Lung Interfacial Films.

    Science.gov (United States)

    Lopez-Rodriguez, Elena; Pascual, Alicia; Arroyo, Raquel; Floros, Joanna; Perez-Gil, Jesus

    2016-08-01

    Pulmonary surfactant is a lipoprotein complex that reduces surface tension to prevent alveolar collapse and contributes to the protection of the respiratory surface from the entry of pathogens. Surfactant protein A (SP-A) is a hydrophilic glycoprotein of the collectin family, and its main function is related to host defense. However, previous studies have shown that SP-A also aids in the formation and biophysical properties of pulmonary surfactant films at the air-water interface. Humans, unlike rodents, have two genes, SFTPA1 and SFTPA2. The encoded proteins, SP-A1 and SP-A2, differ quantitatively or qualitatively in function. It has been shown that both gene products are necessary for tubular myelin formation, an extracellular structural form of lung surfactant. The goal of this study was to investigate potential differences in the biophysical properties of surfactants containing human SP-A1, SP-A2, or both. For this purpose, we have studied for the first time, to our knowledge, the biophysical properties of pulmonary surfactant from individual humanized transgenic mice expressing human SP-A1, SP-A2, or both SP-A1 and SP-A2, in the captive bubble surfactometer. We observed that pulmonary surfactant containing SP-A1 reaches lower surface tension after postexpansion interfacial adsorption than surfactants containing no SP-A or only SP-A2. Under interfacial compression-expansion cycling conditions, surfactant films containing SP-A1 also performed better, particularly with respect to the reorganization of the films that takes place during compression. On the other hand, addition of recombinant SP-A1 to a surfactant preparation reconstituted from the hydrophobic fraction of a porcine surfactant made it more resistant to inhibition by serum than the addition of equivalent amounts of SP-A2. We conclude that the presence of SP-A1 allows pulmonary surfactant to adopt a particularly favorable structure with optimal biophysical properties. PMID:27508436

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

    DEFF Research Database (Denmark)

    Plasencia, I; Cruz, A; López-Lacomba, J L; Casals, C; Pérez-Gil, J

    2001-01-01

    Pulmonary surfactant protein SP-C has been isolated from porcine lungs and treated with dansyl isothiocyanate in chloroform:methanol 2:1 (v/v) solutions,under conditions optimized to introduce a single dansyl group covalently attached to the N-terminalamine group of the protein without loss of its...

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

    DEFF Research Database (Denmark)

    Crouch, Erika C.; Smith, Kelly; McDonald, Barbara; Briner, David; Linders, Bruce; McDonald, Joseph; Holmskov, Uffe; Head, James; Hartshorn, Kevan

    2006-01-01

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

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

    Science.gov (United States)

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

    2013-09-01

    Pulmonary surfactant levels within the alveoli are tightly regulated to maintain lung volumes and promote efficient gas exchange across the air/blood barrier. Quantitative and qualitative abnormalities in surfactant are associated with severe lung diseases in children and adults. Although the cellular and molecular mechanisms that control surfactant metabolism have been studied intensively, the critical molecular pathways that sense and regulate endogenous surfactant levels within the alveolus have not been identified and constitute a fundamental knowledge gap in the field. In this study, we demonstrate that expression of an orphan G protein-coupled receptor, GPR116, in the murine lung is developmentally regulated, reaching maximal levels 1 day after birth, and is highly expressed on the apical surface of alveolar type I and type II epithelial cells. To define the physiological role of GPR116 in vivo, mice with a targeted mutation of the Gpr116 locus, Gpr116(Δexon17), were generated. Gpr116(Δexon17) mice developed a profound accumulation of alveolar surfactant phospholipids at 4 weeks of age (12-fold) that was further increased at 20 weeks of age (30-fold). Surfactant accumulation in Gpr116(Δexon17) mice was associated with increased saturated phosphatidylcholine synthesis at 4 weeks and the presence of enlarged, lipid-laden macrophages, neutrophilia, and alveolar destruction at 20 weeks. mRNA microarray analyses indicated that P2RY2, a purinergic receptor known to mediate surfactant secretion, was induced in Gpr116(Δexon17) type II cells. Collectively, these data support the concept that GPR116 functions as a molecular sensor of alveolar surfactant lipid pool sizes by regulating surfactant secretion. PMID:23590306

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

    Directory of Open Access Journals (Sweden)

    Anna Tarocco

    2015-01-01

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

  14. The detection of surfactant proteins A, B, C and D in the human brain and their regulation in cerebral infarction, autoimmune conditions and infections of the CNS.

    Directory of Open Access Journals (Sweden)

    Stefan Schob

    Full Text Available Surfactant proteins (SP have been studied intensively in the respiratory system. Surfactant protein A and surfactant protein D are proteins belonging to the family of collectins each playing a major role in the innate immune system. The ability of surfactant protein A and surfactant protein D to bind various pathogens and facilitate their elimination has been described in a vast number of studies. Surfactant proteins are very important in modulating the host's inflammatory response and participate in the clearance of apoptotic cells. Surfactant protein B and surfactant protein C are proteins responsible for lowering the surface tension in the lungs. The aim of this study was an investigation of expression of surfactant proteins in the central nervous system to assess their specific distribution patterns. The second aim was to quantify surfactant proteins in cerebrospinal fluid of healthy subjects compared to patients suffering from different neuropathologies. The expression of mRNA for the surfactant proteins was analyzed with RT-PCR done with samples from different parts of the human brain. The production of the surfactant proteins in the brain was verified using immunohistochemistry and Western blot. The concentrations of the surfactant proteins in cerebrospinal fluid from healthy subjects and patients suffering from neuropathologic conditions were quantified using ELISA. Our results revealed that surfactant proteins are present in the central nervous system and that the concentrations of one or more surfactant proteins in healthy subjects differed significantly from those of patients affected by central autoimmune processes, CNS infections or cerebral infarction. Based on the localization of the surfactant proteins in the brain, their different levels in normal versus pathologic samples of cerebrospinal fluid and their well-known functions in the lungs, it appears that the surfactant proteins may play roles in host defense of the brain

  15. Sputum and BAL Clara cell secretory protein and surfactant protein D levels in asthma.

    Science.gov (United States)

    Emmanouil, P; Loukides, S; Kostikas, K; Papatheodorou, G; Papaporfyriou, A; Hillas, G; Vamvakaris, I; Triggidou, R; Katafigiotis, P; Kokkini, A; Papiris, S; Koulouris, N; Bakakos, P

    2015-06-01

    Clara cell secretory protein (CC16) is associated with Th2 modulation. Surfactant protein D (SPD) plays an important role in surfactant homeostasis and eosinophil chemotaxis. We measured CC16 and SPD in sputum supernatants of 84 asthmatic patients and 12 healthy controls. In 22 asthmatics, we additionally measured CC16 and SPD levels in BAL and assessed smooth muscle area (SMA), reticular basement membrane (RBM) thickness, and epithelial detachment (ED) in bronchial biopsies. Induced sputum CC16 and SPD were significantly higher in patients with severe asthma (SRA) compared to mild-moderate and healthy controls. BAL CC16 and SPD levels were also higher in SRA compared to mild-moderate asthma. CC16 BAL levels correlated with ED, while SPD BAL levels correlated with SMA and RBM. Severity represented a significant covariate for these associations. CC16 and SPD levels are upregulated in SRA and correlate with remodeling indices, suggesting a possible role of these biomarkers in the remodeling process. PMID:25728058

  16. Aerosol delivery of synthetic lung surfactant

    Directory of Open Access Journals (Sweden)

    Frans J. Walther

    2014-05-01

    Full Text Available Background. Nasal continuous positive airway pressure (nCPAP is a widely accepted technique of non-invasive respiratory support in premature infants with respiratory distress syndrome due to lack of lung surfactant. If this approach fails, the next step is often intubation, mechanical ventilation (MV and intratracheal instillation of clinical lung surfactant. Objective. To investigate whether aerosol delivery of advanced synthetic lung surfactant, consisting of peptide mimics of surfactant proteins B and C (SP-B and SP-C and synthetic lipids, during nCPAP improves lung function in surfactant-deficient rabbits. Methods. Experimental synthetic lung surfactants were produced by formulating 3% Super Mini-B peptide (SMB surfactant, a highly surface active SP-B mimic, and a combination of 1.5% SMB and 1.5% of the SP-C mimic SP-Css ion-lock 1 (BC surfactant, with a synthetic lipid mixture. After testing aerosol generation using a vibrating membrane nebulizer and aerosol conditioning (particle size, surfactant composition and surface activity, we investigated the effects of aerosol delivery of synthetic SMB and BC surfactant preparations on oxygenation and lung compliance in saline-lavaged, surfactant-deficient rabbits, supported with either nCPAP or MV. Results. Particle size distribution of the surfactant aerosols was within the 1–3 µm distribution range and surfactant activity was not affected by aerosolization. At a dose equivalent to clinical surfactant therapy in premature infants (100 mg/kg, aerosol delivery of both synthetic surfactant preparations led to a quick and clinically relevant improvement in oxygenation and lung compliance in the rabbits. Lung function recovered to a greater extent in rabbits supported with MV than with nCPAP. BC surfactant outperformed SMB surfactant in improving lung function and was associated with higher phospholipid values in bronchoalveolar lavage fluid; these findings were irrespective of the type of

  17. On the significance of Surfactant Protein-A within the human lungs

    OpenAIRE

    Lang Dagmar S; Abdullah Mahdi; Schultz Holger; Kähler Daniel; Goldmann Torsten; Stellmacher Florian; Vollmer Ekkehard

    2009-01-01

    Abstract Surfactant Protein-A (SP-A) is the most prominent among four proteins in the pulmonary surfactant-system. SP-A is expressed by alveolar epithelial cells type II as well as by a portion of non small cell lung carcinomas (NSCLC). The expression of SP-A is complexly regulated on the transcriptional and the chromosomal level. SP-A is a major player in the pulmonary cytokine-network and moreover has been described to act in the pulmonary host defense. By the use of cell culture or animal ...

  18. Solubility versus Electrostatics: What Determines Lipid/Protein Interaction in Lung Surfactant

    OpenAIRE

    Seifert, M.; Breitenstein, D. (Daniel); Klenz, U.; Meyer, M. C.; Galla, H.-J.

    2007-01-01

    Mammalian lung surfactant is a complex lipid/protein mixture covering the alveolar interface and has the crucial function of reducing the surface tension at this boundary to minimal values. Surfactant protein SP-B plays an important role for this purpose and was the focus of many recent studies. However, the specificity of lipid/SP-B interactions is controversial. Since these investigations were accomplished at varying pH conditions (pH 5.5 and 7.0), we studied the specificity of these intera...

  19. 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;

    2005-01-01

    Surfactant protein D (SP-D) plays important roles in the host defense against infectious microorganisms and in regulating the innate immune response to a variety of pathogen-associated molecular pattern. SP-D is mainly expressed by type II cells of the lung, but SP-D is generally found on epithel......Surfactant protein D (SP-D) plays important roles in the host defense against infectious microorganisms and in regulating the innate immune response to a variety of pathogen-associated molecular pattern. SP-D is mainly expressed by type II cells of the lung, but SP-D is generally found...

  20. Discrimination of Proteins Using an Array of Surfactant-Stabilized Gold Nanoparticles.

    Science.gov (United States)

    Rogowski, Jacob L; Verma, Mohit S; Gu, Frank X

    2016-08-01

    Protein analysis is a fundamental aspect of biochemical research. Gold nanoparticles are an emerging platform for various biological applications given their high surface area, biocompatibility, and unique optical properties. The colorimetric properties of gold nanoparticles make them ideal for point-of-care diagnostics. Different aspects of gold nanoparticle-protein interactions have been investigated to predict the effect of protein adsorption on colloidal stability, but the role of surfactants is often overlooked, despite their potential to alter both protein and nanoparticle properties. Herein we present a method by which gold nanoparticles can be prepared in various surfactants and used for array-based quantification and identification of proteins. The exchange of surfactant not only changed the zeta potential of those gold nanoparticles but also drastically altered their aggregation response to five different proteins (bovine serum albumin, human serum albumin, immunoglobulin G, lysozyme, and hemoglobin) in a concentration-dependent manner. Finally, we demonstrate that varying surfactant concentration can be used to control assay sensitivity. PMID:27399345

  1. Solubilizing and Stabilizing Proteins in Anhydrous Ionic Liquids through Formation of Protein-Polymer Surfactant Nanoconstructs.

    Science.gov (United States)

    Brogan, Alex P S; Hallett, Jason P

    2016-04-01

    Nonaqueous biocatalysis is rapidly becoming a desirable tool for chemical and fuel synthesis in both the laboratory and industry. Similarly, ionic liquids are increasingly popular anhydrous reaction media for a number of industrial processes. Consequently, the use of enzymes in ionic liquids as efficient, environment-friendly, commercial biocatalysts is highly attractive. However, issues surrounding the poor solubility and low stability of enzymes in truly anhydrous media remain a significant challenge. Here, we demonstrate for the first time that engineering the surface of a protein to yield protein-polymer surfactant nanoconstructs allows for dissolution of dry protein into dry ionic liquids. Using myoglobin as a model protein, we show that this method can deliver protein molecules with near native structure into both hydrophilic and hydrophobic anhydrous ionic liquids. Remarkably, using temperature-dependent synchrotron radiation circular dichroism spectroscopy to measure half-denaturation temperatures, our results show that protein stability increases by 55 °C in the ionic liquid as compared to aqueous solution, pushing the solution thermal denaturation beyond the boiling point of water. Therefore, the work presented herein could provide a platform for the realization of biocatalysis at high temperatures or in anhydrous solvent systems. PMID:26976718

  2. 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

  3. Establishment of LC-MS methods for the analysis of palmitoylated surfactant proteins.

    Science.gov (United States)

    Harayama, Takeshi; Shindou, Hideo; Kita, Yoshihiro; Otsubo, Eiji; Ikeda, Kazushige; Chida, Shoichi; Weaver, Timothy E; Shimizu, Takao

    2015-07-01

    The surfactant proteins (SPs), SP-B and SP-C, are important components of pulmonary surfactant involved in the reduction of alveolar surface tension. Quantification of SP-B and SP-C in surfactant drugs is informative for their quality control and the evaluation of their biological activity. Western blot analysis enabled the quantification of SP-B, but not SP-C, in surfactant drugs. Here, we report a new procedure involving chemical treatments and LC-MS to analyze SP-C peptides. The procedure enabled qualitative analysis of SP-C from different species with discrimination of the palmitoylation status and the artificial modifications that occur during handling and/or storage. In addition, the method can be used to estimate the total amount of SP-C in pulmonary surfactant drugs. The strategy described here might serve as a prototype to establish analytical methods for peptides that are extremely hydrophobic and behave like lipids. The new method provides an easy measurement of SP-C from various biological samples, which will help the characterization of various experimental animal models and the quality control of surfactant drugs, as well as diagnostics of human samples. PMID:26022805

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

    Directory of Open Access Journals (Sweden)

    Rizzi Sabina

    2011-03-01

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

  5. Expression of surfactant protein-A in exhaled breath condensate of patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Lin, Xue-Feng; Zhang, Lei; Shi, Shu-Yuan; Fan, Yi-Chu; Wu, Zhen-Lin; Zhang, Xun; Sun, Da-Qiang

    2016-02-01

    Pulmonary surfactant protein A (SP-A) has been associated with host defense in the lung, and contributes to the pathogenesis of chronic obstructive pulmonary disease (COPD). The present study aimed to determine a non‑invasive method of measurement of SP‑A, and further examine the expression levels of SP‑A in patients with COPD. SP‑A was detected in the exhaled breath condensate (EBC) obtained from patients with COPD and from non‑COPD subjects. The individuals recruited for the present study comprised 60 subjects with and without COPD, who underwent lobectomy for a solitary peripheral lung nodule. EBC was collected using a condenser, and an enzyme‑linked immunosorbent assay (ELISA) was used to measure the levels of SP‑A. Tissue samples were obtained during lobectomy through resection of the adjacent lung tissues, located >5 cm from the nodule. Western blot analysis and immunohistochemistry were used to measure SP‑A and SP‑A‑positive type II pneumocytes. The results demonstrated that SP‑A was detectable in the EBC of all subjects. The results of the ELISA and western blotting demonstrated that the expression levels of SP‑A were significantly decreased in patients with COPD, compared with the non‑COPD subjects. The reduction of SP‑A‑positive type II pneumocytes was associated with the expression levels of SP‑A. Decreased expression levels of SP‑A in EBC were associated with a higher degree of airway limitation. These results suggested that the measurement of SP‑A levels in the EBC may serve as a method for monitoring airway obstruction in patients with COPD. Further investigations are required in order to examine these observations further and to elucidate the underlying mechanisms. PMID:26707652

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-01

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

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

    International Nuclear Information System (INIS)

    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, α-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-β-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 correlation of

  8. Binding sites for interaction of peroxiredoxin 6 with surfactant protein A.

    Science.gov (United States)

    Krishnaiah, Saikumari Y; Dodia, Chandra; Sorokina, Elena M; Li, Haitao; Feinstein, Sheldon I; Fisher, Aron B

    2016-04-01

    Peroxiredoxin 6 (Prdx6) is a bifunctional enzyme with peroxidase and phospholipase A2 (PLA2) activities. This protein participates in the degradation and remodeling of internalized dipalmitoylphosphatidylcholine (DPPC), the major phospholipid component of lung surfactant. We have shown previously that the PLA2 activity of Prdx6 is inhibited by the lung surfactant-associated protein called surfactant protein A (SP-A) through direct protein-protein interaction. Docking of SPA and Prdx6 was modeled using the ZDOCK (zlab.bu.edu) program in order to predict molecular sites for binding of the two proteins. The predicted peptide sequences were evaluated for binding to the opposite protein using isothermal titration calorimetry and circular dichroism measurement followed by determination of the effect of the SP-A peptide on the PLA2 activity of Prdx6. The sequences 195EEEAKKLFPK204.in the Prdx6 helix and 83DEELQTELYEIKHQIL99 in SP-A were identified as the sites for hydrophobic interaction and H(+)-bonding between the 2 proteins. Treatment of mouse endothelial cells with the SP-A peptide inhibited their recovery from lipid peroxidation associated with oxidative stress indicating inhibition of Prdx6 activity by the peptide in the intact cell. PMID:26723227

  9. Involvement of surfactant protein D in emphysema revealed by genetic association study

    OpenAIRE

    Ishii, Takeo; Hagiwara, Koichi; Kamio, Koichiro; Ikeda, Shinobu; Arai, Tomio; Mieno, Makiko Naka; Kumasaka, Toshio; Muramatsu, Masaaki; Sawabe, Motoji; Gemma, Akihiko; Kida, Kozui

    2011-01-01

    Surfactant protein D (SFTPD) induces emphysema in knockout mice, but the association of SFTPD with chronic obstructive pulmonary disease (COPD) and emphysema in humans is unclear. Therefore, we aimed to determine the association between genetic variations in SFTPD and susceptibility to COPD and emphysema.

  10. 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; Chamat, Soulaima; Waked, Mirna; Holmskov, Uffe; Sorensen, Grith L; Nadif, Rachel; Salameh, Pascale

    2016-01-01

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

  11. Capillary electromigration separation of proteins and microorganisms dynamically modified by chromophoric nonionogenic surfactant

    Czech Academy of Sciences Publication Activity Database

    Horká, Marie; Růžička, F.; Holá, V.; Kahle, Vladislav; Moravcová, Dana; Šlais, Karel

    2009-01-01

    Roč. 81, č. 16 (2009), s. 6897-6904. ISSN 0003-2700 R&D Projects: GA AV ČR IAAX00310701 Institutional research plan: CEZ:AV0Z40310501 Keywords : capillary electromigration techniques * yellow nonionogenic surfactant * proteins and microorganisms in the urine Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 5.214, year: 2009

  12. Intratracheal Recombinant Surfactant Protein D Prevents Endotoxin Shock in the Newborn Preterm Lamb

    OpenAIRE

    Ikegami, Machiko; Carter, Karen; Bishop, Kimberly; Yadav, Annuradha; Masterjohn, Elizabeth; Brondyk, William; Scheule, Ronald K.; Jeffrey A Whitsett

    2006-01-01

    Rationale: The susceptibility of neonates to pulmonary and systemic infection has been associated with the immaturity of both lung structure and the immune system. Surfactant protein (SP) D is a member of the collectin family of innate immune molecules that plays an important role in innate host defense of the lung.

  13. A ToF-SIMS study of the lateral organization of lipids and proteins in pulmonary surfactant systems

    OpenAIRE

    Keating, Eleonora; Alan J Waring; Walther, Frans J; Possmayer, Fred; Veldhuizen, Ruud A. W.; Petersen, Nils O.

    2010-01-01

    Pulmonary surfactant is a complex lipid–protein mixture whose main function is to reduce the surface tension at the air–liquid interface of alveoli to minimize the work of breathing. The exact mechanism by which surfactant monolayers and multilayers are formed and how they lower surface tension to very low values during lateral compression remains uncertain. We used time-of-flight secondary ion mass spectrometry to study the lateral organization of lipids and peptide in surfactant preparation...

  14. Surfactant Protein A Enhances Constitutive Immune Functions of Clathrin Heavy Chain and Clathrin Adaptor Protein 2.

    Science.gov (United States)

    Moulakakis, Christina; Steinhäuser, Christine; Biedziak, Dominika; Freundt, Katja; Reiling, Norbert; Stamme, Cordula

    2016-07-01

    NF-κB transcription factors are key regulators of pulmonary inflammatory disorders and repair. Constitutive lung cell type- and microenvironment-specific NF-κB/inhibitor κBα (IκB-α) regulation, however, is poorly understood. Surfactant protein (SP)-A provides both a critical homeostatic and lung defense control, in part by immune instruction of alveolar macrophages (AMs) via clathrin-mediated endocytosis. The central endocytic proteins, clathrin heavy chain (CHC) and the clathrin adaptor protein (AP) complex AP2, have pivotal alternative roles in cellular homeostasis that are endocytosis independent. Here, we dissect endocytic from alternative functions of CHC, the α-subunit of AP2, and dynamin in basal and SP-A-modified LPS signaling of macrophages. As revealed by pharmacological inhibition and RNA interference in primary AMs and RAW264.7 macrophages, respectively, CHC and α-adaptin, but not dynamin, prevent IκB-α degradation and TNF-α release, independent of their canonical role in membrane trafficking. Kinetics studies employing confocal microscopy, Western analysis, and immunomagnetic sorting revealed that SP-A transiently enhances the basal protein expression of CHC and α-adaptin, depending on early activation of protein kinase CK2 (former casein kinase II) and Akt1 in primary AMs from rats, SP-A(+/+), and SP-A(-/-) mice, as well as in vivo when intratracheally administered to SP-A(+/+) mice. Constitutive immunomodulation by SP-A, but not SP-A-mediated inhibition of LPS-induced NF-κB activity and TNF-α release, requires CHC, α-adaptin, and dynamin. Our data demonstrate that endocytic proteins constitutively restrict NF-κB activity in macrophages and provide evidence that SP-A enhances the immune regulatory capacity of these proteins, revealing a previously unknown pathway of microenvironment-specific NF-κB regulation in the lung. PMID:26771574

  15. Interaction of Pulmonary Surfactant Protein C with CD14 and Lipopolysaccharide

    OpenAIRE

    Augusto, Luis A.; Synguelakis, Monique; Johansson, Jan; Pedron, Thierry; Girard, Robert; Chaby, Richard

    2003-01-01

    In addition to their effects on alveolar surface tension, some components of lung surfactant also have immunological functions. We found recently that the hydrophobic lung surfactant protein SP-C specifically binds to the lipid A region of lipopolysaccharide (LPS). In this study, we show that SP-C also interacts with CD14. Four observations showed cross talk between the three molecules SP-C, LPS, and CD14. (i) Like LBP, SP-C allows the binding of a fluorescent LPS to cells expressing CD14 (th...

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

    Science.gov (United States)

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

    2015-06-15

    The paper describes the adsorption of purified protein from seeds of Moringa oleifera to a sapphire interface and the effects of addition of the anionic surfactant sodium dodecylsulfate (SDS) and the cationic surfactant hexadecyltrimethylammonium bromide (CTAB). Neutron reflection was used to determine the structure and composition of interfacial layers adsorbed at the solid/solution interface. The maximum surface excess of protein was found to be about 5.3 mg m(-2). The protein does not desorb from the solid/liquid interface when rinsed with water. Addition of SDS increases the reflectivity indicating co-adsorption. It was observed that CTAB is able to remove the protein from the interface. The distinct differences to the behavior observed previously for the protein at the silica/water interface are identified. The adsorption of the protein to alumina in addition to other surfaces has shown why it is an effective flocculating agent for the range of impurities found in water supplies. The ability to tailor different surface layers in combination with various surfactants also offers the potential for adsorbed protein to be used in separation technologies. PMID:25746187

  17. “SP-G”, a Putative New Surfactant Protein – Tissue Localization and 3D Structure

    OpenAIRE

    Rausch, Felix; Schicht, Martin; Paulsen, Friedrich; Ngueya, Ivan; Bräuer, Lars; Brandt, Wolfgang

    2012-01-01

    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 putativ...

  18. The role of surfactant proteins in DPPC enrichment of surface films.

    OpenAIRE

    Veldhuizen, E J; Batenburg, J.J.; van Golde, L M; Haagsman, H.P.

    2000-01-01

    A pressure-driven captive bubble surfactometer was used to determine the role of surfactant proteins in refinement of the surface film. The advantage of this apparatus is that surface films can be spread at the interface of an air bubble with a different lipid/protein composition than the subphase vesicles. Using different combinations of subphase vesicles and spread surface films a clear correlation between dipalmitoylphosphatidylcholine (DPPC) content and minimum surface tension was observe...

  19. STRUCTURE, FUNCTION AND DEFICIENCY DISEASES OF LUNG SURFACTANT PROTEIN-C

    Directory of Open Access Journals (Sweden)

    Anita Gupta and GS Gupta*

    2014-01-01

    Full Text Available Pulmonary surfactant is a mixture of lipids and hydrophobic surfactant proteins B (SP-B and SP-C and hydrophilic proteins SP-A and SP-D. Pulmonary surfactant reduces the surface tension at the air-water interface of the lung alveoli by forming a surface active film. In this way, it prevents alveoli from collapsing and facilitates the process of breathing. SP-C cooperates with SP-B to enhance the surface active properties of surfactant phospholipids. Reports on the association of lung disease with SP-C deficiency have led to new insights into the importance of SP-C for proper surfactant homeostasis. In most animal species the major form of SP-C is a 35-residue peptide chain which contains two thioester-linked palmitoyl groups, giving a total molecular mass of 4.2 kDa. Though the function of SP-C in vivo remains unclear, but effects of SP-C on the adsorption, spreading, and stability of lipid films at an air ⁄ water interface have been documented in a number of in vitro studies. Genetic disorders disrupting normal surfactant metabolism (surfactant dysfunction disorders have been recognized in the neonatal and pediatric populations. Although rare, these disorders cause significant mortality and morbidity, including acute respiratory distress and failure in full-term neonates, and interstitial lung disease (ILD in older infants, children, and adults.  The genes involved in these disorders are critical for surfactant production and function in the lung and include SP-C gene (SFTPC besides others. More than 40 mutations in the SFTPC gene have been identified in people with dysfunction of lung surfactant. Mutations in the SFTPC gene result in the reduction or absence of mature SP-C and accumulation of abnormal forms of SP-C, resulting into breathing problems in newborns and onset of breathing difficulties in children and adults. SFTPC gene mutations associated with surfactant dysfunction affect the processing of the SP-C protein. Many of these

  20. 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.

  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

    2008-01-01

    In order to confirm the alteration and significance of cigarette smoke exposure on SP-A in rats, 20 Wistar rats were assigned randomly to two groups: an N group (n=10), and an S group (n=10). The ultra-structural change was observed by electron microscopy. The number of cells positive for SPA was by immunohistochemically measured. The mRNA expression in the lung tissues was deter-mined by reverse transcription polymerase chain reaction (RT-PCR). The number of cells positive for SPA of the S group (0.52±0.05) was lower than that of the N group (0.72±0.06) (P<0.05). The lev-els of mRNA of SPA in the lung tissues of the S group (0.3522±0.0512) was significantly lower than that of the N group (0.4432±0.05628) (P<0.05). It is concluded that cigarette smoke alone decreased the level of SP-A and that might have an important effect on surfactant metabolism and the host deense functions of surfactant in the peripheral airways, which might play a crucial role in the devel-opment of chronic obstructive lung disease.

  2. Glucocorticoid regulation of human pulmonary surfactant protein-B (SP-B) mRNA stability is independent of activated glucocorticoid receptor.

    Science.gov (United States)

    Tillis, Ceá C; Huang, Helen W; Bi, Weizhen; Pan, Su; Bruce, Shirley R; Alcorn, Joseph L

    2011-06-01

    Adequate expression of surfactant protein-B (SP-B) is critical in the function of pulmonary surfactant to reduce alveolar surface tension. Expression of SP-B mRNA is restricted to specific lung-airway epithelial cells, and human SP-B mRNA stability is increased in the presence of the synthetic glucocorticoid dexamethasone (DEX). Although the mechanism of SP-B mRNA stabilization by DEX is unknown, studies suggest involvement of the glucocorticoid receptor (GR). We developed a dual-cistronic plasmid-based expression assay in which steady-state levels of SP-B mRNA, determined by Northern analysis, reproducibly reflect changes in SP-B mRNA stability. Using this assay, we found that steady-state levels of SP-B mRNA increased greater than twofold in transfected human-airway epithelial cells (A549) incubated with DEX (10(-7) M). DEX-mediated changes in SP-B mRNA levels required the presence of the SP-B mRNA 3'-untranslated region but did not require ongoing protein synthesis. The effect of DEX on SP-B mRNA levels was dose dependent, with maximal effect at 10(-7) M. DEX increased levels of SP-B mRNA in cells lacking GR, and the presence of the GR antagonist RU486 did not interfere with the effect of DEX. Surprisingly, other steroid hormones (progesterone, estradiol, and vitamin D; 10(-7) M) significantly increased SP-B mRNA levels, suggesting a common pathway of steroid hormone action on SP-B mRNA stability. These results indicate that the effect of DEX to increase SP-B mRNA stability is independent of activated GR and suggests that the mechanism is mediated by posttranscriptional or nongenomic effects of glucocorticoids. PMID:21398497

  3. A ToF-SIMS study of the lateral organization of lipids and proteins in pulmonary surfactant systems.

    Science.gov (United States)

    Keating, Eleonora; Waring, Alan J; Walther, Frans J; Possmayer, Fred; Veldhuizen, Ruud A W; Petersen, Nils O

    2011-03-01

    Pulmonary surfactant is a complex lipid-protein mixture whose main function is to reduce the surface tension at the air-liquid interface of alveoli to minimize the work of breathing. The exact mechanism by which surfactant monolayers and multilayers are formed and how they lower surface tension to very low values during lateral compression remains uncertain. We used time-of-flight secondary ion mass spectrometry to study the lateral organization of lipids and peptide in surfactant preparations ranging in complexity. We show that we can successfully determine the location of phospholipids, cholesterol and a peptide in surfactant Langmuir-Blodgett films and we can determine the effect of cholesterol and peptide addition. A thorough understanding of the lateral organization of PS interfacial films will aid in our understanding of the role of each component as well as different lipid-lipid and lipid-protein interactions. This may further our understanding of pulmonary surfactant function. PMID:21110942

  4. Photoreversible conformational changes in membrane proteins using light-responsive surfactants.

    Science.gov (United States)

    Zhang, Jing; Wang, Shao-Chun; Lee, C Ted

    2009-06-25

    Photoreversible control of the conformation of bacteriorhodopsin in the presence of a light-responsive surfactant is demonstrated through combined UV-vis, FT-IR, and (31)P NMR spectroscopy and dynamic light scattering (DLS) measurements. The azobenzene-based surfactant photoisomerizes upon 434 nm visible (trans, relatively hydrophobic) and 350 nm UV (cis, relatively hydrophilic) illumination, allowing surfactant micellization to be reversibly controlled. This leads to partitioning of the membrane protein into micelles in the unfolded state under visible light, while UV light leads to solubilization of the protein within purple membrane bilayers in the folded state. A three-stage model of purple membrane-photosurfactant interactions is examined through NMR and DLS measurements. Phototriggered unfolding of bacteriorhodopsin, occurring through alpha(II) --> alpha(I) and reverse beta-turn --> extended beta-strand transitions, requires approximately 20 s for completion, while light-induced refolding requires a somewhat longer 80 s as the membrane protein repartitions into the reformed bilayer membrane. Each of these conformational changes can be precisely and reversibly controlled with simple light illumination, providing a novel technique to probe membrane protein folding. PMID:19485396

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

    Directory of Open Access Journals (Sweden)

    Rhona E McDonald

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

  6. Alveolar Type II cell transplantation restores pulmonary surfactant protein levels in lung fibrosis

    OpenAIRE

    Guillamat-Prats, Raquel; Gay-Jordi, Gemma; Xaubet, Antoni; Peinado, Victor; Serrano-Mollar, Anna

    2014-01-01

    Background Alveolar Type II cell transplantation has been proposed as a cell therapy for the treatment of idiopathic pulmonary fibrosis. Its long-term benefits include repair of lung fibrosis, but its success partly depends on the restoration of lung homeostasis. Our aim was to evaluate surfactant protein restoration after alveolar Type II cell transplantation in an experimental model of bleomycin-induced lung fibrosis in rats. Methods Lung fibrosis was induced by intratracheal instillation o...

  7. Surfactant protein C-deficient mice are susceptible to respiratory syncytial virus infection

    OpenAIRE

    Glasser, Stephan W.; Witt, Teah L.; Senft, Albert P; Baatz, John E.; Folger, Dusti; Melissa D. Maxfield; Akinbi, Henry T.; Newton, Danforth A.; Prows, Daniel R.; Korfhagen, Thomas R.

    2009-01-01

    Patients with mutations in the pulmonary surfactant protein C (SP-C) gene develop interstitial lung disease and pulmonary exacerbations associated with viral infections including respiratory syncytial virus (RSV). Pulmonary infection with RSV caused more severe interstitial thickening, air space consolidation, and goblet cell hyperplasia in SP-C-deficient (Sftpc−/−) mice compared with SP-C replete mice. The RSV-induced pathology resolved more slowly in Sftpc−/− mice with lung inflammation per...

  8. Genetic replacement of surfactant protein-C reduces respiratory syncytial virus induced lung injury

    OpenAIRE

    Glasser, Stephan W.; Senft, Albert P; Melissa D. Maxfield; Ruetschilling, Teah L.; Baatz, John E.; Page, Kristen; Korfhagen, Thomas R.

    2013-01-01

    Background Individuals with deficiencies of pulmonary surfactant protein C (SP-C) develop interstitial lung disease (ILD) that is exacerbated by viral infections including respiratory syncytial virus (RSV). SP-C gene targeted mice (Sftpc -/-) lack SP-C, develop an ILD-like disease and are susceptible to infection with RSV. Methods In order to determine requirements for correction of RSV induced injury we have generated compound transgenic mice where SP-C expression can be induced on the Sftpc...

  9. Aqueous solubilization of C60 fullerene by natural protein surfactants, latherin and ranaspumin-2

    OpenAIRE

    Vance, Steven J.; Desai, Vibhuti; Smith, Brian O.; Kennedy, Malcolm W.; Cooper, Alan

    2016-01-01

    C60 fullerene is not soluble in water and dispersion usually requires organic solvents, sonication or vigorous mechanical mixing. However, we show here that mixing of pristine C60 in water with natural surfactant proteins latherin and ranaspumin-2 (Rsn-2) at low concentrations yields stable aqueous dispersions with spectroscopic properties similar to those previously obtained by more vigorous methods. Particle sizes are significantly smaller than those achieved by mechanical dispersion alone,...

  10. Hypoxia-Induced Mitogenic Factor Modulates Surfactant Protein B and C Expression in Mouse Lung

    OpenAIRE

    Tong, Qiangsong; Zheng, Liduan; Dodd-o, Jeffrey; Langer, John; Wang, Danming; Li, Dechun

    2005-01-01

    Previous studies have demonstrated a robust pulmonary expression of hypoxia-induced mitogenic factor (HIMF) during the perinatal period, when surfactant protein (SP) synthesis begins. We hypothesized that HIMF modulates SP expression and participates in lung development and maturation. The temporal-spatial expression of HIMF, SP-B, and SP-C in developing mouse lungs was examined by immunohistochemical staining, Western blot, and RT-PCR. The expression and localization of SP-B and SP-C were in...

  11. Molecular Dynamics Simulations of a Pulmonary Surfactant Protein B Peptide in a Lipid Monolayer

    OpenAIRE

    Freites, J. Alfredo; Choi, Yunsoo; Tobias, Douglas J.

    2003-01-01

    Pulmonary surfactant is a complex mixture of lipids and proteins that lines the air/liquid interface of the alveolar hypophase and confers mechanical stability to the alveoli during the breathing process. The desire to formulate synthetic mixtures for low-cost prophylactic and therapeutic applications has motivated the study of the specific roles and interactions of the different components. All-atom molecular dynamics simulations were carried out on a model system composed of a monolayer of ...

  12. The surfactant protein C mutation A116D alters cellular processing, stress tolerance, surfactant lipid composition, and immune cell activation

    Directory of Open Access Journals (Sweden)

    Zarbock Ralf

    2012-03-01

    Full Text Available Abstract Background Surfactant protein C (SP-C is important for the function of pulmonary surfactant. Heterozygous mutations in SFTPC, the gene encoding SP-C, cause sporadic and familial interstitial lung disease (ILD in children and adults. Mutations mapping to the BRICHOS domain located within the SP-C proprotein result in perinuclear aggregation of the proprotein. In this study, we investigated the effects of the mutation A116D in the BRICHOS domain of SP-C on cellular homeostasis. We also evaluated the ability of drugs currently used in ILD therapy to counteract these effects. Methods SP-CA116D was expressed in MLE-12 alveolar epithelial cells. We assessed in vitro the consequences for cellular homeostasis, immune response and effects of azathioprine, hydroxychloroquine, methylprednisolone and cyclophosphamide. Results Stable expression of SP-CA116D in MLE-12 alveolar epithelial cells resulted in increased intracellular accumulation of proSP-C processing intermediates. SP-CA116D expression further led to reduced cell viability and increased levels of the chaperones Hsp90, Hsp70, calreticulin and calnexin. Lipid analysis revealed decreased intracellular levels of phosphatidylcholine (PC and increased lyso-PC levels. Treatment with methylprednisolone or hydroxychloroquine partially restored these lipid alterations. Furthermore, SP-CA116D cells secreted soluble factors into the medium that modulated surface expression of CCR2 or CXCR1 receptors on CD4+ lymphocytes and neutrophils, suggesting a direct paracrine effect of SP-CA116D on neighboring cells in the alveolar space. Conclusions We show that the A116D mutation leads to impaired processing of proSP-C in alveolar epithelial cells, alters cell viability and lipid composition, and also activates cells of the immune system. In addition, we show that some of the effects of the mutation on cellular homeostasis can be antagonized by application of pharmaceuticals commonly applied in ILD therapy

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    assessment of patients, prediction of risk, and guidance of treatment. The aim of this review is to provide a comprehensive summary of observations for a selection of recently investigated pulmonary inflammatory biomarkers (Surfactant protein D (SP-D), Club cell protein 16 (CC-16), and Pulmonary and...

  14. Surfactant protein D in the female genital tract

    DEFF Research Database (Denmark)

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

    2004-01-01

    -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...

  15. Infant formula alters surfactant protein A (SP-A) and SP-B expression in pulmonary epithelial cells.

    Science.gov (United States)

    Chen, Maurice G; Atkins, Constance L; Bruce, Shirley R; Khan, Amir M; Liu, Yuying; Alcorn, Joseph L

    2011-09-01

    Surfactant proteins A (SP-A) and SP-B are critical in the ability of pulmonary surfactant to reduce alveolar surface tension and provide innate immunity. Aspiration of infant milk formula can lead to lung dysfunction, but direct effects of aspirated formula on surfactant protein expression in pulmonary cells have not been described. The hypothesis that infant formula alters surfactant protein homeostasis was tested in vitro by assessing surfactant protein gene expression in cultured pulmonary epithelial cell lines expressing SP-A and SP-B that were transiently exposed (6 hr) to infant formula. Steady-state levels of SP-A protein and mRNA and SP-B mRNA in human bronchiolar (NCI-H441) and mouse alveolar (MLE15) epithelial cells were reduced in a dose-dependent manner 18 hr after exposure to infant formula. SP-A mRNA levels remained reduced 42 hr after exposure, but SP-B mRNA levels increased 10-fold. Neither soy formula nor non-fat dry milk affected steady-state SP-A and SP-B mRNA levels; suggesting a role of a component of infant formula derived from cow milk. These results indicate that infant formula has a direct, dose-dependent effect to reduce surfactant protein gene expression. Ultimately, milk aspiration may potentially result in a reduced capacity of the lung to defend against environmental insults. PMID:21520433

  16. Nuclear matrix binding protein SMAR1 regulates T-cell differentiation and allergic airway disease.

    Science.gov (United States)

    Chemmannur, S V; Badhwar, A J; Mirlekar, B; Malonia, S K; Gupta, M; Wadhwa, N; Bopanna, R; Mabalirajan, U; Majumdar, S; Ghosh, B; Chattopadhyay, S

    2015-11-01

    Asthma is a complex airway allergic disease involving the interplay of various cell types, cytokines, and transcriptional factors. Though many factors contribute to disease etiology, the molecular control of disease phenotype and responsiveness is not well understood. Here we report an essential role of the matrix attachment region (MAR)-binding protein SMAR1 in regulating immune response during allergic airway disease. Conditional knockout of SMAR1 in T cells rendered the mice resistant to eosinophilic airway inflammation against ovalbumin (OVA) allergen with low immunoglobulin E (IgE) and interleukin-5 (IL-5) levels. Moreover, a lower IgE/IgG2a ratio and higher interferon-γ (IFN-γ) response suggested aberrant skewing of T-cell differentiation toward type 1 helper T cell (Th1) response. We show that SMAR1 functions as a negative regulator of Th1 and Th17 differentiation by interacting with two potential and similar MAR regions present on the promoters of T-bet and IL-17. Thus, we present SMAR1 as a regulator of T-cell differentiation that favors the establishment of Th2 cells by modulating Th1 and Th17 responses. PMID:25736456

  17. Surfactant Proteins A, B, C and D in the Human Nasal Airway

    DEFF Research Database (Denmark)

    Gaunsbaek, Maria Q; Kjeldsen, Anette D; Svane-Knudsen, Viggo; Henriksen, Maiken L; Hansen, Soren

    2014-01-01

    Surgery, Odense University Hospital, Denmark. The study included 39 subjects. Nasal mucosal biopsies were analyzed by immunohistochemistry, and bronchoalveolar and nasal lavages, nasal brush biopsies and nasal mucus were analyzed for SP-A, -B, -C and -D by SDS-PAGE and Western blotting. The presence of SP-A...... and SP-D in the first three samplings were also analyzed by enzyme-linked immunosorbent assay. Results: In nasal mucosal biopsies, SP-A, -B, -C and -D were all demonstrated in the serous acini of the submucosal glands and in the surface epithelium. SP-D was detected in nasal brush biopsies, whereas...... the other SPs were absent. Moreover, SP-A, -B, -C and -D were absent in nasal lavage and mucus. Conclusion: SP-A, -B, -C and -D exert their protective effect in the ductal epithelium of the submucosal glands rather than in nasal secretions and mucus. Further studies are required to clarify the...

  18. Processing, stability and interactions of lung surfactant protein C

    OpenAIRE

    Li, Jing

    2005-01-01

    Mature SP-C is a 4.2 kDa transmembrane protein which is uniquely expressed in the alveolar type II cell. Human SP-C is generated via multistep proteolytic cleavage of both the C-terminal and Nterminal regions of proSP-C. The function of SP-C in vivo remains unclear, but effects of SP-C on the adsorption, spreading, and stability of lipid films at an air/water interface have been documented in a number of in vitro studies. Infants with inherited deficiency of SP-B and SP-...

  19. Human Surfactant Protein – A Gene Locus for Genetic Studies in the Finnish Population

    Directory of Open Access Journals (Sweden)

    Mika Rämet

    2000-01-01

    Full Text Available Lung surfactant lowers the surface tension but surfactant proteins also have other functions. Surfactant protein A (SP-A has a well-defined role in innate immunity. The gene locus for human SP-A genes is in chromosome 10q21 through q24 and consists of two highly homologous functional SP-A genes (SP-A1 and SP-A2 and a pseudogene. Several alleles that differ by a single amino acid have been identified for both SP-A genes. The SP-A gene locus has been shown to be sufficiently polymorphic for genetic studies in the American population. In this study, we analysed the SP-A allele frequencies in a Finnish population (n = 790 and found them to differ from the frequencies observed in US. Furthermore, we describe several new alleles for both SP-A genes. The heterozygosity indices and polymorphism information content values ranged between 0.50–0.62 indicating that SP-A gene locus is polymorphic enough for studies associating the locus with pulmonary diseases.

  20. 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.

  1. Surfactant Protein A Suppresses Lung Cancer Progression by Regulating the Polarization of Tumor-Associated Macrophages

    OpenAIRE

    Mitsuhashi, Atsushi; Goto, Hisatsugu; Kuramoto, Takuya; Tabata, Sho; Yukishige, Sawaka; Abe, Shinji; Hanibuchi, Masaki; Kakiuchi, Soji; Saijo, Atsuro; Aono, Yoshinori; Uehara, Hisanori; Yano, Seiji; Ledford, Julie G.; Sone, Saburo; Nishioka, Yasuhiko

    2013-01-01

    Surfactant protein A (SP-A) is a large multimeric protein found in the lungs. In addition to its immunoregulatory function in infectious respiratory diseases, SP-A is also used as a marker of lung adenocarcinoma. Despite the finding that SP-A expression levels in cancer cells has a relationship with patient prognosis, the function of SP-A in lung cancer progression is unknown. We investigated the role of SP-A in lung cancer progression by introducing the SP-A gene into human lung adenocarcino...

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

    DEFF Research Database (Denmark)

    Zhao, X M; Wu, Y P; Wei, R; Cai, H X; Tornoe, I; Han, J J; Wang, Y; de Groot, P G; Holmskov, U; Xia, Z L; Sørensen, Grith Lykke

    2007-01-01

    significant effect of age, and (iii) a significant inverse association between serum SP-D and body mass index (BMI) (P = 0.012). The data indicate that racial differences in SP-D expression exist as the median plasma SP-D in the Chinese population was approximately two times lower than the median serum SP......Surfactant protein D (SP-D) is a member of the collectin family and is an important component of the pulmonary innate host defence. The protein has a widespread distribution in the human body and is present in multiple epithelia, in endothelium and in blood. Various studies have looked at the...

  3. Biological, pathobiological and bioclinical bases of pulmonary surfactant metabolism in the human species

    International Nuclear Information System (INIS)

    The surfactant metabolism dysfunction pulmonary (SMDP), classically termed as Pulmonary Alveolar Proteinosis (PAP) are a unusual respiratory disorder characterized by abundant and excessive accumulation of surfactant-derived phospholipids and protein components in the pulmonary alveoli and distal airways, with disturbances associated secondary of pulmonary gas exchange and engendering respiratory insufficiency. At least three general pathophysiologic mechanisms may lead to the characteristic feature of PAP: Primary (idiopathic, essential, acquired or adult), secondary and congenital.

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

    Science.gov (United States)

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

    2015-10-01

    The silk protein surfactant (SPS) first used as a silk degumming agent in this study is an amino acid-type anionic surfactant that was synthesized using silk fibroin amino acids and lauroyl chloride. We studied it systematically in comparison with the traditional degumming methods such as sodium carbonate (Na2CO3) and neutral soap (NS). The experimental results showed that the sericin can be completely removed from the silk fibroin fiber after boiling the fibers three times for 30 min and using a bath ratio of 1:80 (g/mL) and a concentration of 0.2% SPS in an aqueous solution. The results of the tensile properties, thermal analysis, and SEM all show that SPS is similar to the NS, far superior to Na2CO3. In short, SPS may be used as an environmentally friendly silk degumming/refining agent in the silk textile industry and in the manufacture of silk floss quilts. PMID:26117747

  5. Airway Hyperresponsiveness in Asthma Model Occurs Independently of Secretion of β1 Integrins in Airway Wall and Focal Adhesions Proteins Down Regulation.

    Science.gov (United States)

    Álvarez-Santos, Mayra; Carbajal, Verónica; Tellez-Jiménez, Olivia; Martínez-Cordero, Erasmo; Ruiz, Victor; Hernández-Pando, Rogelio; Lascurain, Ricardo; Santibañez-Salgado, Alfredo; Bazan-Perkins, Blanca

    2016-10-01

    The extracellular domains of some membrane proteins can be shed from the cell. A similar phenomenon occurs with β1 integrins (α1β1 and α2β1) in guinea pig. The putative role of β1 integrin subunit alterations due to shedding in airway smooth muscle (ASM) in an allergic asthma model was evaluated. Guinea pigs were sensitized and challenged with antigen. Antigenic challenges induced bronchoobstruction and hyperresponsiveness at the third antigenic challenge. Immunohistochemistry and immunoelectronmicroscopy studies showed that the cytosolic and extracellular domains of the β1 integrin subunit shared the same distribution in airway structures in both groups. Various polypeptides with similar molecular weights were detected with both the cytosolic and extracellular β1 integrin subunit antibodies in isolated airway myocytes and the connective tissue that surrounds the ASM bundle. Flow cytometry and Western blot studies showed that the expression of cytosolic and extracellular β1 integrin subunit domains in ASM was similar between groups. An increment of ITGB1 mRNA in ASM was observed in the asthma model group. RACE-PCR of ITGB1 in ASM did not show splicing variants. The expression levels of integrin-linked kinase (ILK) and paxillin diminished in the asthma model, but not talin. The levels of phosphorylation of myosin phosphatase target subunit 1 (MYPT1) at Thr(696) increased in asthma model. Our work suggests that β1 integrin is secreted in guinea pig airway wall. This secretion is not altered in asthma model; nevertheless, β1 integrin cytodomain assembly proteins in focal cell adhesions in which ILK and paxillin are involved are altered in asthma model. J. Cell. Biochem. 117: 2385-2396, 2016. © 2016 Wiley Periodicals, Inc. PMID:26969873

  6. Hypoxia-inducible factor regulates expression of surfactant protein in alveolar type II cells in vitro.

    Science.gov (United States)

    Ito, Yoko; Ahmad, Aftab; Kewley, Emily; Mason, Robert J

    2011-11-01

    Alveolar type II (ATII) cells cultured at an air-liquid (A/L) interface maintain differentiation, but they lose these properties when they are submerged. Others showed that an oxygen tension gradient develops in the culture medium as ATII cells consume oxygen. Therefore, we wondered whether hypoxia inducible factor (HIF) signaling could explain differences in the phenotypes of ATII cells cultured under A/L interface or submerged conditions. ATII cells were isolated from male Sprague-Dawley rats and cultured on inserts coated with a mixture of rat-tail collagen and Matrigel, in medium including 5% rat serum and 10 ng/ml keratinocyte growth factor, with their apical surfaces either exposed to air or submerged. The A/L interface condition maintained the expression of surfactant proteins, whereas that expression was down-regulated under the submerged condition, and the effect was rapid and reversible. Under submerged conditions, there was an increase in HIF1α and HIF2α in nuclear extracts, mRNA levels of HIF inducible genes, vascular endothelial growth factor, glucose transporter-1 (GLUT1), and the protein level of pyruvate dehydrogenase kinase isozyme-1. The expression of surfactant proteins was suppressed and GLUT1 mRNA levels were induced when cells were cultured with 1 mM dimethyloxalyl glycine. The expression of surfactant proteins was restored under submerged conditions with supplemented 60% oxygen. HIF signaling and oxygen tension at the surface of cells appears to be important in regulating the phenotype of rat ATII cells. PMID:21454802

  7. Association between the surfactant protein A (SP-A) gene locus and respiratory-distress syndrome in the Finnish population.

    OpenAIRE

    Rämet, M; Haataja, R.; Marttila, R; Floros, J; Hallman, M

    2000-01-01

    Respiratory-distress syndrome (RDS) in the newborn is a major cause of neonatal mortality and morbidity. Although prematurity is the most-important risk factor for RDS, the syndrome does not develop in many premature infants. The main cause of RDS is a deficiency of pulmonary surfactant, which consists of phospholipids and specific proteins. The genes underlying susceptibility to RDS are insufficiently known. The candidate-gene approach was used to study the association between the surfactant...

  8. Aqueous solubilization of C60 fullerene by natural protein surfactants, latherin and ranaspumin-2.

    Science.gov (United States)

    Vance, Steven J; Desai, Vibhuti; Smith, Brian O; Kennedy, Malcolm W; Cooper, Alan

    2016-01-01

    C60 fullerene is not soluble in water and dispersion usually requires organic solvents, sonication or vigorous mechanical mixing. However, we show here that mixing of pristine C60 in water with natural surfactant proteins latherin and ranaspumin-2 (Rsn-2) at low concentrations yields stable aqueous dispersions with spectroscopic properties similar to those previously obtained by more vigorous methods. Particle sizes are significantly smaller than those achieved by mechanical dispersion alone, and concentrations are compatible with clusters approximating 1:1 protein:C60 stoichiometry. These proteins can also be adsorbed onto more intractable carbon nanotubes. This promises to be a convenient way to interface a range of hydrophobic nanoparticles and related materials with biological macromolecules, with potential to exploit the versatility of recombinant protein engineering in the development of nano-bio interface devices. It also has potential consequences for toxicological aspects of these and similar nanoparticles. PMID:27214760

  9. Evaluation of the Effectiveness of Surfactants and Denaturants to Elute and Denature Adsorbed Protein on Different Surface Chemistries.

    Science.gov (United States)

    Thyparambil, Aby A; Wei, Yang; Latour, Robert A

    2015-11-01

    The elution and/or denaturation of proteins from material surfaces by chemical excipients such as surfactants and denaturants is important for numerous applications including medical implant reprocessing, bioanalyses, and biodefense. The objective of this study was to develop and apply methods to quantitatively assess how surface chemistry and adsorption conditions influence the effectiveness of three commonly used surfactants (sodium dodecyl sulfate, n-octyl-β-d-glucoside, and 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate) and two denaturants (guanidium hydrochloride and urea) to elute protein (hen egg white lysozyme and bovine pancreatic ribonuclease A) from three different surface chemistries (silica glass, poly(methyl methacrylate), and high-density polyethylene). The structure and bioactivity of residual protein on the surface following elution were characterized using circular dichroism spectropolarimetry and enzyme assays to assess the extent of protein denaturation. Our results indicate that the denaturants were generally more effective than the surfactants in removing the adsorbed proteins from each type of surface. Also, the denaturing capacity of these excipients on the residual proteins on the surfaces was distinctly different from their influence on the proteins in solution and was unique for each of the adsorption conditions. Taken altogether, these results reveal that the effectiveness of surfactants and denaturants to elute and denature adsorbed protein is significantly influenced by surface chemistry and the conditions from which the protein was adsorbed. These results provide a basis for the selection, design, and further development of chemical agents for protein elution and surface decontamination. PMID:26449787

  10. A nonionic surfactant-decorated liquid crystal sensor for sensitive and selective detection of proteins.

    Science.gov (United States)

    Wang, Yi; Hu, Qiongzheng; Tian, Tongtong; Gao, Yan'an; Yu, Li

    2016-09-21

    Proteins are responsible for most biochemical events in human body. It is essential to develop sensitive and selective methods for the detection of proteins. In this study, liquid crystal (LC)-based sensor for highly selective and sensitive detection of lysozyme, concanavalin A (Con A), and bovine serum albumin (BSA) was constructed by utilizing the LC interface decorated with a nonionic surfactant, dodecyl β-d-glucopyranoside. A change of the LC optical images from bright to dark appearance was observed after transferring dodecyl β-d-glucopyranoside onto the aqueous/LC interface due to the formation of stable self-assembled surfactant monolayer, regardless of pH and ion concentrations studied in a wide range. The optical images turned back from dark to bright appearance after addition of lysozyme, Con A and BSA, respectively. Noteworthy is that these proteins can be further distinguished by adding enzyme inhibitors and controlling incubation temperature of the protein solutions based on three different interaction mechanisms between proteins and dodecyl β-d-glucopyranoside, viz. enzymatic hydrolysis, specific saccharide binding, and physical absorption. The LC-based sensor decorated with dodecyl β-d-glucopyranoside shows high sensitivity for protein detection. The limit of detection (LOD) for lysozyme, Con A and BSA reaches around 0.1 μg/mL, 0.01 μg/mL and 0.001 μg/mL, respectively. These results might provide new insights into increasing selectivity and sensitivity of LC-based sensors for the detection of proteins. PMID:27590553

  11. Close mimicry of lung surfactant protein B by “clicked” dimers of helical, cationic peptoids

    OpenAIRE

    Dohm, Michelle T.; Seurynck-Servoss, Shannon L.; Seo, Jiwon; Zuckermann, Ronald N.; Barron, Annelise E.

    2009-01-01

    A family of peptoid dimers developed to mimic SP-B is presented, where two amphipathic, cationic helices are linked by an achiral octameric chain. SP-B is a vital therapeutic protein in lung surfactant replacement therapy, but its large-scale isolation or chemical synthesis is impractical. Enhanced biomimicry of SP-B’s disulfide-bonded structure has been previously attempted via disulfide-mediated dimerization of SP-B1-25 and other peptide mimics, which improved surface activity relative to t...

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

    Directory of Open Access Journals (Sweden)

    Julien Perino

    2013-03-01

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

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

    DEFF Research Database (Denmark)

    Cruz, A; Casals, C; Plasencia, I;

    1998-01-01

    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 t...

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

    DEFF Research Database (Denmark)

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

    2004-01-01

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

  15. Low molecular weight human pulmonary surfactant protein (SP5): isolation, characterization, and cDNA and amino acid sequences

    International Nuclear Information System (INIS)

    Pulmonary surfactant is a lipid-protein complex that promotes alveolar stability by lowering the surface tension at the air-fluid interface in the peripheral air spaces. A group of hydrophobic surfactant-associated proteins has been shown to be essential for rapid surface film formation by surfactant phospholipids. The authors have purified a hydrophobic surfactant protein of ≅ 5kDa that they term SP5 from bronchopulmonary lavage fluid from a patient with alveolar proteinosis and shown that it promotes rapid surface film formation by simple mixtures of phospholipids. They have derived the full amino acid sequence of human SP5 from the nucleotide sequence of cDNAs identified with oligonucleotide probes based on the NH2-terminal sequence of SP5. SP5 isolated from surfactant is a fragment of a much larger precursor protein (21 kDa). The precursor contains an extremely hydrophobic region of 34 amino acids that comprises most the mature SP5. This hydrophobicity explains the unusual solubility characteristics of SP5 and the fact that it is lipid-associated when isolated from lung

  16. Low molecular weight human pulmonary surfactant protein (SP5): isolation, characterization, and cDNA and amino acid sequences

    Energy Technology Data Exchange (ETDEWEB)

    Warr, R.G.; Hawgood, S.; Buckley, D.I.; Crisp, T.M.; Schilling, J.; Benson, B.J.; Ballard, P.L.; Clements, J.A.; White, R.T.

    1987-11-01

    Pulmonary surfactant is a lipid-protein complex that promotes alveolar stability by lowering the surface tension at the air-fluid interface in the peripheral air spaces. A group of hydrophobic surfactant-associated proteins has been shown to be essential for rapid surface film formation by surfactant phospholipids. The authors have purified a hydrophobic surfactant protein of approx. = 5kDa that they term SP5 from bronchopulmonary lavage fluid from a patient with alveolar proteinosis and shown that it promotes rapid surface film formation by simple mixtures of phospholipids. They have derived the full amino acid sequence of human SP5 from the nucleotide sequence of cDNAs identified with oligonucleotide probes based on the NH/sub 2/-terminal sequence of SP5. SP5 isolated from surfactant is a fragment of a much larger precursor protein (21 kDa). The precursor contains an extremely hydrophobic region of 34 amino acids that comprises most the mature SP5. This hydrophobicity explains the unusual solubility characteristics of SP5 and the fact that it is lipid-associated when isolated from lung.

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

    Directory of Open Access Journals (Sweden)

    Sho Hideshima

    2016-03-01

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

  18. 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.

  19. Increased and prolonged pulmonary fibrosis in surfactant protein C-deficient mice following intratracheal bleomycin.

    Science.gov (United States)

    Lawson, William E; Polosukhin, Vasiliy V; Stathopoulos, Georgios T; Zoia, Ornella; Han, Wei; Lane, Kirk B; Li, Bo; Donnelly, Edwin F; Holburn, George E; Lewis, Kenneth G; Collins, Robert D; Hull, William M; Glasser, Stephan W; Whitsett, Jeffrey A; Blackwell, Timothy S

    2005-11-01

    Recent reports have linked mutations in the surfactant protein C gene (SFTPC) to familial forms of pulmonary fibrosis, but it is uncertain whether deficiency of mature SP-C contributes to disease pathogenesis. In this study, we evaluated bleomycin-induced lung fibrosis in mice with genetic deletion of SFTPC. Compared with wild-type (SFTPC+/+) controls, mice lacking surfactant protein C (SFTPC-/-) had greater lung neutrophil influx at 1 week after intratracheal bleomycin, greater weight loss during the first 2 weeks, and increased mortality. At 3 and 6 weeks after bleomycin, lungs from SFTPC-/- mice had increased fibroblast numbers, augmented collagen accumulation, and greater parenchymal distortion. Furthermore, resolution of fibrosis was delayed. Although remodeling was near complete in SFTPC+/+ mice by 6 weeks, SFTPC-/- mice did not return to baseline until 9 weeks after bleomycin. By terminal dUTP nick-end labeling staining, widespread cell injury was observed in SFTPC-/- and SFTPC+/+ mice 1 week after bleomycin; however, ongoing apoptosis of epithelial and interstitial cells occurred in lungs of SFTPC-/- mice, but not SFTPC+/+ mice, 6 weeks after bleomycin. Thus, SP-C functions to limit lung inflammation, inhibit collagen accumulation, and restore normal lung structure after bleomycin. PMID:16251411

  20. Solution structure of the coiled-coil trimerization domain from lung surfactant protein D

    Energy Technology Data Exchange (ETDEWEB)

    Kovacs, Helena [Bruker BioSpin AG (Switzerland); O' Donoghue, Sean I. [European Molecular Biology Laboratory (Germany); Hoppe, Hans-Juergen [University of Oxford, MRC Immunochemistry Unit (United Kingdom); Comfort, David [University of Oxford, Department of Biochemistry (United Kingdom); Reid, Kenneth B.M. [University of Oxford, MRC Immunochemistry Unit (United Kingdom); Campbell, Iain D. [University of Oxford, Department of Biochemistry (United Kingdom); Nilges, Michael [European Molecular Biology Laboratory (Germany)], E-mail: nilges@pasteur.fr

    2002-10-15

    Surfactant protein D (SP-D) is one of four known protein components of the pulmonary surfactant lining the lung alveoli. It is involved in immune and allergic responses. SP-D occurs as a tetramer of trimers. Trimerization is thought to be initiated by a coiled coil domain. We have determined the solution structure of a 64-residue peptide encompassing the coiled coil domain of human SP-D. As predicted, the domain forms a triple-helical parallel coiled coil. As with all symmetric oligomers, the structure calculation was complicated by the symmetry degeneracy in the NMR spectra. We used the symmetry-ADR (ambiguous distance restraint) structure calculation method to solve the structure. The results demonstrate that the leucine zipper region of SP-D is an autonomously folded domain. The structure is very similar to the independently determined X-ray crystal structure, differing mainly at a single residue, Tyr248. This residue is completely symmetric in the solution structure, and markedly asymmetric in the crystalline phase. This difference may be functionally important, as it affects the orientation of the antigenic surface presented by SP-D.

  1. Solution structure of the coiled-coil trimerization domain from lung surfactant protein D

    International Nuclear Information System (INIS)

    Surfactant protein D (SP-D) is one of four known protein components of the pulmonary surfactant lining the lung alveoli. It is involved in immune and allergic responses. SP-D occurs as a tetramer of trimers. Trimerization is thought to be initiated by a coiled coil domain. We have determined the solution structure of a 64-residue peptide encompassing the coiled coil domain of human SP-D. As predicted, the domain forms a triple-helical parallel coiled coil. As with all symmetric oligomers, the structure calculation was complicated by the symmetry degeneracy in the NMR spectra. We used the symmetry-ADR (ambiguous distance restraint) structure calculation method to solve the structure. The results demonstrate that the leucine zipper region of SP-D is an autonomously folded domain. The structure is very similar to the independently determined X-ray crystal structure, differing mainly at a single residue, Tyr248. This residue is completely symmetric in the solution structure, and markedly asymmetric in the crystalline phase. This difference may be functionally important, as it affects the orientation of the antigenic surface presented by SP-D

  2. Recruited alveolar macrophages, in response to airway epithelial-derived monocyte chemoattractant protein 1/CCl2, regulate airway inflammation and remodeling in allergic asthma.

    Science.gov (United States)

    Lee, Yong Gyu; Jeong, Jong Jin; Nyenhuis, Sharmilee; Berdyshev, Evgeny; Chung, Sangwoon; Ranjan, Ravi; Karpurapu, Manjula; Deng, Jing; Qian, Feng; Kelly, Elizabeth A B; Jarjour, Nizar N; Ackerman, Steven J; Natarajan, Viswanathan; Christman, John W; Park, Gye Young

    2015-06-01

    Although alveolar macrophages (AMs) from patients with asthma are known to be functionally different from those of healthy individuals, the mechanism by which this transformation occurs has not been fully elucidated in asthma. The goal of this study was to define the mechanisms that control AM phenotypic and functional transformation in response to acute allergic airway inflammation. The phenotype and functional characteristics of AMs obtained from human subjects with asthma after subsegmental bronchoprovocation with allergen was studied. Using macrophage-depleted mice, the role and trafficking of AM populations was determined using an acute allergic lung inflammation model. We observed that depletion of AMs in a mouse allergic asthma model attenuates Th2-type allergic lung inflammation and its consequent airway remodeling. In both human and mouse, endobronchial challenge with allergen induced a marked increase in monocyte chemotactic proteins (MCPs) in bronchoalveolar fluid, concomitant with the rapid appearance of a monocyte-derived population of AMs. Furthermore, airway allergen challenge of allergic subjects with mild asthma skewed the pattern of AM gene expression toward high levels of the receptor for MCP1 (CCR2/MCP1R) and expression of M2 phenotypic proteins, whereas most proinflammatory genes were highly suppressed. CCL2/MCP-1 gene expression was prominent in bronchial epithelial cells in a mouse allergic asthma model, and in vitro studies indicate that bronchial epithelial cells produced abundant MCP-1 in response to house dust mite allergen. Thus, our study indicates that bronchial allergen challenge induces the recruitment of blood monocytes along a chemotactic gradient generated by allergen-exposed bronchial epithelial cells. PMID:25360868

  3. 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

    2012-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-03-01

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

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

    International Nuclear Information System (INIS)

    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-radiological 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.)

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

    OpenAIRE

    Kajiki Akira; Fukushima Kazuo; Kawabata Masaharu; Wakamatsu Kentaro; Kitasato Yasuhiko; Nagata Nobuhiko; Kitahara Yoshinari; Watanabe Kentaro

    2011-01-01

    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...

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

    OpenAIRE

    Nagata, Nobuhiko; Kitasato, Yasuhiko; Wakamatsu, Kentaro; Kawabata, Masaharu; Fukushima, Kazuo; Kajiki, Akira; Kitahara, Yoshinari; Watanabe, Kentaro

    2011-01-01

    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 ai...

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    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...... and airway fluids, as well as in blood and various mucosal locations, and could, like MBL, play a role in restricting HIV transmission or replication in vivo.......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...

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

    NARCIS (Netherlands)

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

    1991-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Guttentag Susan

    2005-07-01

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

  11. Developmental regulation of chicken surfactant protein A and its localization in lung.

    Science.gov (United States)

    Zhang, Weidong; Cuperus, Tryntsje; van Dijk, Albert; Skjødt, Karsten; Hansen, Søren; Haagsman, Henk P; Veldhuizen, Edwin J A

    2016-08-01

    Surfactant Protein A (SP-A) is a collagenous C-type lectin (collectin) that plays an important role in the early stage of the host immune response. In chicken, SP-A (cSP-A) is expressed as a 26 kDa glycosylated protein in the lung. Using immunohistochemistry, cSP-A protein was detected mainly in the lung lining fluid covering the parabronchial epithelia. Specific cSP-A producing epithelial cells, resembling mammalian type II cells, were identified in the parabronchi. Gene expression of cSP-A markedly increased from embryonic day 14 onwards until the time of hatch, comparable to the SP-A homologue chicken lung lectin, while mannan binding lectin and collectins CL-L1 and CL-K1 only showed slightly changed expression during development. cSP-A protein could be detected as early as ED 18 in lung tissue using Western blotting, and expression increased steadily until day 28 post-hatch. Our observations are a first step towards understanding the role of this protein in vivo. PMID:26976230

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

    Science.gov (United States)

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

    2015-12-01

    Surfactant protein D (SP-D) is a pulmonary collectin important in lung immunity. SP-D-deficient mice (Sftpd(-/-)) are reported to be susceptible to ovalbumin (OVA)- and fungal allergen-induced pulmonary inflammation, while treatment with exogenous SP-D has therapeutic effects in such disease models. β-Glucans are a diverse group of polysaccharides previously suggested to serve as fungal ligands for SP-D. We set out to investigate if SP-D could interact with 1,3-β-glucan and attenuate allergic pulmonary inflammation in the presence of 1,3-β-glucan. Allergic airway disease was induced in Sftpd(-/-) and Sftpd(+/+) mice by OVA sensitization and subsequent challenge with OVA, 1,3-β-glucan, or OVA/1,3-β-glucan together. Mice in the combined treatment group were further treated with a high dose of recombinant fragment of human SP-D (rfhSP-D). We demonstrated direct interaction between SP-D and 1,3-β-glucan. OVA-induced mucous cell metaplasia was increased in Sftpd(-/-) mice, supporting previously reported protective effects of endogenous SP-D in allergy. OVA-induced parenchymal CCL11 levels and eosinophilic infiltration in bronchoalveolar lavage were unaffected by 1,3-β-glucan, but were reversed with rfhSP-D treatment. 1,3-β-Glucan treatment did, however, induce pulmonary neutrophilic infiltration and increased TNF-α levels in bronchoalveolar lavage, independently of OVA-induced allergy. This infiltration was also reversed by treatment with rfhSP-D. 1,3-β-Glucan reduced OVA-induced mucous cell metaplasia, T helper 2 cytokines, and IFN-γ production. rfhSP-D treatment further reduced mucous metaplasia and T helper 2 cytokine secretion to background levels. In summary, rfhSP-D treatment resulted in attenuation of both allergic inflammation and 1,3-β-glucan-mediated neutrophilic inflammation. Our data suggest that treatment with high-dose SP-D protects from mold-induced exacerbations of allergic asthma. PMID:26432866

  13. A-kinase-anchoring proteins coordinate inflammatory responses to cigarette smoke in airway smooth muscle.

    Science.gov (United States)

    Poppinga, Wilfred J; Heijink, Irene H; Holtzer, Laura J; Skroblin, Philipp; Klussmann, Enno; Halayko, Andrew J; Timens, Wim; Maarsingh, Harm; Schmidt, Martina

    2015-04-15

    β2-Agonist inhibitors can relieve chronic obstructive pulmonary disease (COPD) symptoms by stimulating cyclic AMP (cAMP) signaling. A-kinase-anchoring proteins (AKAPs) compartmentalize cAMP signaling by establishing protein complexes. We previously reported that the β2-agonist fenoterol, direct activation of protein kinase A (PKA), and exchange factor directly activated by cAMP decrease cigarette smoke extract (CSE)-induced release of neutrophil attractant interleukin-8 (IL-8) from human airway smooth muscle (ASM) cells. In the present study, we tested the role of AKAPs in CSE-induced IL-8 release from ASM cells and assessed the effect of CSE on the expression levels of different AKAPs. We also studied mRNA and protein expression of AKAPs in lung tissue from patients with COPD. Our data show that CSE exposure of ASM cells decreases AKAP5 and AKAP12, both capable of interacting with β2-adrenoceptors. In lung tissue of patients with COPD, mRNA levels of AKAP5 and AKAP12 were decreased compared with lung tissue from controls. Using immunohistochemistry, we detected less AKAP5 protein in ASM of patients with COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II compared with control subjects. St-Ht31, which disrupts AKAP-PKA interactions, augmented CSE-induced IL-8 release from ASM cells and diminished its suppression by fenoterol, an effect mediated by disturbed ERK signaling. The modulatory role of AKAP-PKA interactions in the anti-inflammatory effects of fenoterol in ASM cells and the decrease in expression of AKAP5 and AKAP12 in response to cigarette smoke and in lungs of patients with COPD suggest that cigarette smoke-induced changes in AKAP5 and AKAP12 in patients with COPD may affect efficacy of pharmacotherapy. PMID:25637608

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

  15. Influence of levofloxacin on soluble selection, interleukin, adhesion molecule and pulmonary surfactant protein of patients with pulmonary tuberculosis

    Institute of Scientific and Technical Information of China (English)

    Qing-Zhou He; Qian-Shu Hu

    2016-01-01

    Objective:To observe the influence of levofloxacin on soluble selection, interleukin, adhesion molecule and pulmonary surfactant protein of patients with pulmonary tuberculosis. Methods:A total of 50 patients with pulmonary tuberculosis who had been treated in our hospital from March 2014 to April 2015 were randomly divided into the control group (conventional treatment) and the observation group (conventional treatment plus levofloxacin). Each group had 25 cases. Then, the soluble selection,interleukin,adhesion molecule and pulmonary surfactant protein levels of the two groups at the second, fourth and sixth months before and after treatment were compared. Results:Before treatment, the differencess of the levels of the soluble selection, interleukin, adhesion molecule and pulmonary surfactant protein of the two groups were significant (P>0.05), while the detection levels of all the aspects of the observation group at the second, fourth and sixth months after treatment were all significantly lower than those of the control group (P<0.05). The detection results of the two groups at the second, fourth and sixth months after treatment showed significant differences. Conclusions:Lvofloxacin has significant effect on the soluble selection, interleukin, adhesion molecule and pulmonary surfactant protein of patients with pulmonary tuberculosis.

  16. Chemotherapy Modulates Intestinal Immune Gene Expression Including Surfactant Protein-D and Deleted in Malignant Brain Tumors 1 in Piglets

    DEFF Research Database (Denmark)

    Rathe, Mathias; Thomassen, Mads; Shen, René L.; Pontoppidan, Peter E L; Husby, Steffen; Müller, Klaus; Kruse, Torben A.; Sangild, Per T.

    BUCY and DOX piglets. Selected genes of potential biological significance with a similar change in expression across the treatments were controlled by real-time polymerase chain reaction. Key innate defense molecules, including surfactant protein-D and deleted in malignant brain tumors 1, were among...

  17. Surfactant protein D augments bacterial association but attenuates major histocompatibility complex class II presentation of bacterial antigens

    DEFF Research Database (Denmark)

    Hansen, Søren; Lo, Bernice; Evans, Kathy;

    2006-01-01

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    Development of dementia, including Alzheimer's disease (AD), is associated with lipid dysregulation and inflammation. As the host defense lectin surfactant protein D (SP-D) has multiple effects in lipid homeostasis and inflammation, the correlation between SP-D concentrations and development of...... CRP showed that Odds Ratio for developing dementia was 2.62 (1.12-6.15) with an SP-D concentration in the highest quartile compared to the other quartiles. The risk of AD was 2.55 (0.95-6.90). Cox regression controlling for the same variables showed that hazard ratio of death was 1.43 (1.06-1.92) in...... the highest quartile. SP-D concentration thus correlates to development of dementia as well as to augmented mortality....

  19. 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; Hansen, Per Lyngs; Hansen, Søren; Holmskov, Uffe; Mouritsen, Ole G

    2007-01-01

    In order to investigate the dynamic strength of the interaction between lung surfactant protein D (SP-D) and different sugars, maltose, mannose, glucose, and galactose, we have used an atomic force microscope to monitor the interaction on a single molecule scale. The experiment is performed by...... measuring the rupture force when the SP-D-sugar bond is subjected to a continuously increasing force. Under these dynamic conditions, SP-D binds strongest to d-mannose and weakest to maltose and d-galactose. These results differ from equilibrium measurements wherein SP-D exhibits preference for maltose. On...... the basis of this finding, we propose that the binding of the disaccharide maltose to SP-D, which is energetically stronger than the binding of any of the monosacchrides, alters the structure of the binding site in a way that lowers the dynamic strength of the bond. We conclude that determining the...

  20. Developmental regulation of chicken surfactant protein A and its localization in lung

    DEFF Research Database (Denmark)

    Zhang, Weidong; Cuperus, Tryntsje; van Dijk, Albert; Skjødt, Karsten; Hansen, Søren Werner Karlskov; Haagsman, Henk P; Veldhuizen, Edwin J A

    2016-01-01

    Surfactant Protein A (SP-A) is a collagenous C-type lectin (collectin) that plays an important role in the early stage of the host immune response. In chicken, SP-A (cSP-A) is expressed as a 26 kDa glycosylated protein in the lung. Using immunohistochemistry, cSP-A protein was detected mainly in...... the lung lining fluid covering the parabronchial epithelia. Specific cSP-A producing epithelial cells, resembling mammalian type II cells, were identified in the parabronchi. Gene expression of cSP-A markedly increased from embryonic day 14 onwards until the time of hatch, comparable to the SP-A...... homologue chicken lung lectin, while mannan binding lectin and collectins CL-L1 and CL-K1 only showed slightly changed expression during development. cSP-A protein could be detected as early as ED 18 in lung tissue using Western blotting, and expression increased steadily until day 28 post-hatch. Our...

  1. Surfactant protein B polymorphisms are associated with severe respiratory syncytial virus infection, but not with asthma

    Directory of Open Access Journals (Sweden)

    Heinzmann Andrea

    2007-05-01

    Full Text Available Abstract Background Surfactant proteins (SP are important for the innate host defence and essential for a physiological lung function. Several linkage and association studies have investigated the genes coding for different surfactant proteins in the context of pulmonary diseases such as chronic obstructive pulmonary disease or respiratory distress syndrome of preterm infants. In this study we tested whether SP-B was in association with two further pulmonary diseases in children, i. e. severe infections caused by respiratory syncytial virus and bronchial asthma. Methods We chose to study five polymorphisms in SP-B: rs2077079 in the promoter region; rs1130866 leading to the amino acid exchange T131I; rs2040349 in intron 8; rs3024801 leading to L176F and rs3024809 resulting in R272H. Statistical analyses made use of the Armitage's trend test for single polymorphisms and FAMHAP and FASTEHPLUS for haplotype analyses. Results The polymorphisms rs3024801 and rs3024809 were not present in our study populations. The three other polymorphisms were common and in tight linkage disequilibrium with each other. They did not show association with bronchial asthma or severe RSV infection in the analyses of single polymorphisms. However, haplotypes analyses revealed association of SP-B with severe RSV infection (p = 0.034. Conclusion Thus our results indicate a possible involvement of SP-B in the genetic predisposition to severe RSV infections in the German population. In order to determine which of the three polymorphisms constituting the haplotypes is responsible for the association, further case control studies on large populations are necessary. Furthermore, functional analysis need to be conducted.

  2. Immunohistochemical Characteristics of Surfactant Proteins A, B, C and D in Inflammatory and Tumorigenic Lung Lesions of F344 Rats

    OpenAIRE

    YOKOHIRA, MASANAO; YAMAKAWA, KEIKO; Nakano, Yuko; Numano, Takamasa; Furukawa, Fumio; Kishi, Sosuke; NINOMIYA, FUMIKO; Kanie, Shohei; Hitotsumachi, Hiroko; Saoo, Kousuke; Imaida, Katsumi

    2014-01-01

    Surfactant proteins (SPs), originally known as human lung surfactants, are essential to respiratory structure and function. There are 4 subtypes, SP-A, SP-B, SP-C and SP-D, with SP-A and SP-D having immunological functions, and SP-B and SP-C having physicochemical properties that reduce the surface tension at biological interfaces. In this experiment, the expressions of SP-A, SP-B, SP-C and SP-D in lung neoplastic lesions induced by N-bis (2-hydroxypropyl) nitrosamine (DHPN) and inflammatory ...

  3. Elucidation of Lipid Binding Sites on Lung Surfactant Protein A Using X-ray Crystallography, Mutagenesis, and Molecular Dynamics Simulations.

    Science.gov (United States)

    Goh, Boon Chong; Wu, Huixing; Rynkiewicz, Michael J; Schulten, Klaus; Seaton, Barbara A; McCormack, Francis X

    2016-07-01

    Surfactant protein A (SP-A) is a collagenous C-type lectin (collectin) that is critical for pulmonary defense against inhaled microorganisms. Bifunctional avidity of SP-A for pathogen-associated molecular patterns (PAMPs) such as lipid A and for dipalmitoylphosphatidylcholine (DPPC), the major component of surfactant membranes lining the air-liquid interface of the lung, ensures that the protein is poised for first-line interactions with inhaled pathogens. To improve our understanding of the motifs that are required for interactions with microbes and surfactant structures, we explored the role of the tyrosine-rich binding surface on the carbohydrate recognition domain of SP-A in the interaction with DPPC and lipid A using crystallography, site-directed mutagenesis, and molecular dynamics simulations. Critical binding features for DPPC binding include a three-walled tyrosine cage that binds the choline headgroup through cation-π interactions and a positively charged cluster that binds the phosphoryl group. This basic cluster is also critical for binding of lipid A, a bacterial PAMP and target for SP-A. Molecular dynamics simulations further predict that SP-A binds lipid A more tightly than DPPC. These results suggest that the differential binding properties of SP-A favor transfer of the protein from surfactant DPPC to pathogen membranes containing appropriate lipid PAMPs to effect key host defense functions. PMID:27324153

  4. The effect of high concentration potassium permanganate on protein contamination from metallic and synthetic rubber airway equipment.

    Science.gov (United States)

    Laupu, W; Brimacombe, J

    2007-08-01

    We tested the hypothesis that supplementary cleaning using potassium permanganate 8 mg.l(-1) eliminates protein deposits from the reusable metallic and synthetic rubber airway equipment. Twenty Macintosh laryngoscope blades (surgical steel), 20 pairs of Magill's forceps (surgical steel) and 20 Guedel airways (synthetic rubber) were allocated to two groups for supplementary cleaning. In group A, the device was immersed in potassium permanganate 8 mg.l(-1). In group B (controls), the device was immersed in sterile water. The devices were then immersed in a protein staining solution, rinsed and the severity of staining was scored. In addition, the devices were inspected for tissue and then tested for occult blood. Protein contamination was lower in the potassium permanganate group for all devices (each device: p cleaning. Additionally, occult blood was detected on two pairs of forceps and a laryngoscope blade, which was not detected following supplementary cleaning. In the control group, no tissue was detected but one pair of forceps and two laryngoscope blades tested positive for occult blood before and after supplementary cleaning. We conclude that supplementary cleaning using potassium permanganate 8 mg.l(-1) eliminates protein deposits from re-usable metallic and synthetic rubber airway equipment. PMID:17635432

  5. High serum concentrations of surfactant protein A in usual interstitial pneumonia compared with non-specific interstitial pneumonia

    OpenAIRE

    Ishii, H; Mukae, H; Kadota, J.; Kaida, H; Nagata, T; Abe, K.; Matsukura, S; Kohno, S.

    2003-01-01

    Background: The pathological diagnosis of interstitial lung diseases (ILD) by surgical lung biopsy is important for clinical decision making. There is a need, however, to use serum markers for differentiating usual interstitial pneumonia (UIP) from other ILD. Surfactant protein (SP)-A, SP-D, KL-6, sialyl SSEA-1 (SLX), and sialyl Lewisa (CA19-9) are useful markers for the diagnosis and evaluation of activity of ILD. We have investigated the usefulness of these proteins as markers of UIP.

  6. Pulmonary surfactant proteins SP-B and SP-C in spread monolayers at the air-water interface: II. Monolayers of pulmonary surfactant protein SP-C and phospholipids.

    OpenAIRE

    Taneva, S; Keough, K M

    1994-01-01

    The interaction of the hydrophobic pulmonary surfactant protein SP-C with dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylglycerol (DPPG) and DPPC:DPPG (7:3, mol:mol) in spread monolayers at the air-water interface has been studied. At low concentrations of SP-C (about 0.5 mol% or 3 weight%protein) the protein-lipid films collapsed at surface pressures of about 70 mN.m-1, comparable to those of the lipids alone. At initial protein concentrations higher than 0.8 mol%, or 4 weight...

  7. Inactivation of pulmonary surfactant and its prevention

    OpenAIRE

    Stichtenoth, Guido

    2009-01-01

    Pulmonary surfactant is a lipoprotein complex coating the conducting airways down to the terminal airspaces. Its main function is to lower surface tension at the air liquid interface thus preventing alveolar collapse at end expiration. Primary surfactant deficiency is the main cause of neonatal respiratory distress syndrome (RDS) and treatment with exogenous pulmonary surfactant improves the course of the disease significantly. Furthermore, secondary surfactant deficiency ca...

  8. Aerosol delivery of synthetic lung surfactant

    OpenAIRE

    Walther, Frans J.; José M. Hernández-Juviel; Waring, Alan J.

    2014-01-01

    Background. Nasal continuous positive airway pressure (nCPAP) is a widely accepted technique of non-invasive respiratory support in premature infants with respiratory distress syndrome due to lack of lung surfactant. If this approach fails, the next step is often intubation, mechanical ventilation (MV) and intratracheal instillation of clinical lung surfactant. Objective. To investigate whether aerosol delivery of advanced synthetic lung surfactant, consisting of peptide mimics of surfact...

  9. Separation of acidic and basic proteins by capillary electrophoresis using gemini surfactants and gemini-capped nanoparticles as buffer additives

    Institute of Scientific and Technical Information of China (English)

    LIU Qian; LI YanQing; YANG YanMin; YAO ShouZhuo

    2009-01-01

    This paper demonstrated simultaneous separation of acidic and basic proteins using cationic gemini surfactants as buffer additives in capillary electrophoresis. We showed that even at a low concentration (0.1 mmol·L~(-1)) of alkanediyl-α,ω-bis(dimethyloctadecylammonium bromide) (18-s-18), the wall adsorp-tion of both acidic and basic proteins could be effectively suppressed under acidic conditions. Smaller micelle size (e.g., s=5-8) is more effective for the separation of acidic proteins than larger micelle size (e.g., s 10). Varying the spacer length of gemini surfactants can influence the electrophoretic mobility and selectivity of proteins to achieve the desired separation. Under the optimized conditions, RSDs of the migration time were less than 0.8% and 2.2% for run-to-run and day-to-day assays, re-spectively, and protein recoveries ranged from 79% to 100.4%. Furthermore, we also investigated the use of gemini surfactant-capped gold nanoparticles (gemini@AuNPs) as buffer additives in protein separation. Introduction of AuNPs into the buffer shortened the analysis time and slightly improved the separation efficiencies. Finally, we presented the applications of this method in the analysis of bio-logical samples, including plasma, red blood cells and egg white.

  10. Separation of acidic and basic proteins by capillary electrophoresis using gemini surfactants and gemini-capped nanoparticles as buffer additives

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    This paper demonstrated simultaneous separation of acidic and basic proteins using cationic gemini surfactants as buffer additives in capillary electrophoresis. We showed that even at a low concentration (0.1 mmol·L-1) of alkanediyl-α,ω-bis(dimethyloctadecylammonium bromide) (18-s-18), the wall adsorption of both acidic and basic proteins could be effectively suppressed under acidic conditions. Smaller micelle size (e.g., s=5-8) is more effective for the separation of acidic proteins than larger micelle size (e.g., s<4 or >10). Varying the spacer length of gemini surfactants can influence the electrophoretic mobility and selectivity of proteins to achieve the desired separation. Under the optimized conditions, RSDs of the migration time were less than 0.8% and 2.2% for run-to-run and day-to-day assays, respectively, and protein recoveries ranged from 79% to 100.4%. Furthermore, we also investigated the use of gemini surfactant-capped gold nanoparticles (gemini@AuNPs) as buffer additives in protein separation. Introduction of AuNPs into the buffer shortened the analysis time and slightly improved the separation efficiencies. Finally, we presented the applications of this method in the analysis of bio-logical samples, including plasma, red blood cells and egg white.

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    (-)D(-) mice have fewer and larger alveoli, an increase in the number and size of type II cells, as well as more numerous and larger alveolar macrophages. More surfactant-storing lamellar bodies are seen in type II cells, leading to a threefold increase in the total volume of lamellar bodies per lung, but the......Alveolar epithelial type II cells synthesize and secrete surfactant. The surfactant-associated proteins A and D (SP-A and SP-D), members of the collectin protein family, participate in pulmonary immune defense, modulation of inflammation, and surfactant metabolism. Both proteins are known to have...... 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...

  12. 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; Serrano, A G; Casals, C; Pérez-Gil, J

    2001-01-01

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

  13. A non-BRICHOS surfactant protein c mutation disrupts epithelial cell function and intercellular signaling

    Directory of Open Access Journals (Sweden)

    Beers Michael F

    2010-11-01

    Full Text Available Abstract Background Heterozygous mutations of SFTPC, the gene encoding surfactant protein C (SP-C, cause sporadic and familial interstitial lung disease (ILD in children and adults. The most frequent SFTPC mutation in ILD patients leads to a threonine for isoleucine substitution at position 73 (I73T of the SP-C preprotein (proSP-C, however little is known about the cellular consequences of SP-CI73T expression. Results To address this, we stably expressed SP-CI73T in cultured MLE-12 alveolar epithelial cells. This resulted in increased intracellular accumulation of proSP-C processing intermediates, which matched proSP-C species recovered in bronchial lavage fluid from patients with this mutation. Exposure of SP-CI73T cells to drugs currently used empirically in ILD therapy, cyclophosphamide, azathioprine, hydroxychloroquine or methylprednisolone, enhanced expression of the chaperones HSP90, HSP70, calreticulin and calnexin. SP-CI73T mutants had decreased intracellular phosphatidylcholine level (PC and increased lyso-PC level without appreciable changes of other phospholipids. Treatment with methylprednisolone or hydroxychloroquine partially restored these lipid alterations. Furthermore, SP-CI73T cells secreted into the medium soluble factors that modulated surface expression of CCR2 or CXCR1 receptors on CD4+ lymphocytes and neutrophils, suggesting a direct paracrine influence of SP-CI73T on neighboring cells in the alveolar space. Conclusion We show that I73T mutation leads to impaired processing of proSP-C in alveolar type II cells, alters their stress tolerance and surfactant lipid composition, and activates cells of the immune system. In addition, we show that some of the mentioned cellular aspects behind the disease can be modulated by application of pharmaceutical drugs commonly applied in the ILD therapy.

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

    OpenAIRE

    Planellas Marta; Cuenca Rafaela; Tabar Maria-Dolores; Bertolani Coralie; Poncet Cyrill; Closa Josep M; Lorente Juan; Cerón Jose J; Pastor Josep

    2012-01-01

    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 obstructiv...

  15. β-Agonist-mediated Relaxation of Airway Smooth Muscle Is Protein Kinase A-dependent*

    Science.gov (United States)

    Morgan, Sarah J.; Deshpande, Deepak A.; Tiegs, Brian C.; Misior, Anna M.; Yan, Huandong; Hershfeld, Alena V.; Rich, Thomas C.; Panettieri, Reynold A.; An, Steven S.; Penn, Raymond B.

    2014-01-01

    Inhaled β-agonists are effective at reversing bronchoconstriction in asthma, but the mechanism by which they exert this effect is unclear and controversial. PKA is the historically accepted effector, although this assumption is made on the basis of associative and not direct evidence. Recent studies have asserted that exchange protein activated by cAMP (Epac), not PKA, mediates the relaxation of airway smooth muscle (ASM) observed with β-agonist treatment. This study aims to clarify the role of PKA in the prorelaxant effects of β-agonists on ASM. Inhibition of PKA activity via expression of the PKI and RevAB peptides results in increased β-agonist-mediated cAMP release, abolishes the inhibitory effect of isoproterenol on histamine-induced intracellular calcium flux, and significantly attenuates histamine-stimulated MLC-20 phosphorylation. Analyses of ASM cell and tissue contraction demonstrate that PKA inhibition eliminates most, if not all, β-agonist-mediated relaxation of contracted smooth muscle. Conversely, Epac knockdown had no effect on the regulation of contraction or procontractile signaling by isoproterenol. These findings suggest that PKA, not Epac, is the predominant and physiologically relevant effector through which β-agonists exert their relaxant effects. PMID:24973219

  16. β-Agonist-mediated relaxation of airway smooth muscle is protein kinase A-dependent.

    Science.gov (United States)

    Morgan, Sarah J; Deshpande, Deepak A; Tiegs, Brian C; Misior, Anna M; Yan, Huandong; Hershfeld, Alena V; Rich, Thomas C; Panettieri, Reynold A; An, Steven S; Penn, Raymond B

    2014-08-15

    Inhaled β-agonists are effective at reversing bronchoconstriction in asthma, but the mechanism by which they exert this effect is unclear and controversial. PKA is the historically accepted effector, although this assumption is made on the basis of associative and not direct evidence. Recent studies have asserted that exchange protein activated by cAMP (Epac), not PKA, mediates the relaxation of airway smooth muscle (ASM) observed with β-agonist treatment. This study aims to clarify the role of PKA in the prorelaxant effects of β-agonists on ASM. Inhibition of PKA activity via expression of the PKI and RevAB peptides results in increased β-agonist-mediated cAMP release, abolishes the inhibitory effect of isoproterenol on histamine-induced intracellular calcium flux, and significantly attenuates histamine-stimulated MLC-20 phosphorylation. Analyses of ASM cell and tissue contraction demonstrate that PKA inhibition eliminates most, if not all, β-agonist-mediated relaxation of contracted smooth muscle. Conversely, Epac knockdown had no effect on the regulation of contraction or procontractile signaling by isoproterenol. These findings suggest that PKA, not Epac, is the predominant and physiologically relevant effector through which β-agonists exert their relaxant effects. PMID:24973219

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

    Science.gov (United States)

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

    2016-09-01

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

  18. Surfactant protein C-deficient mice are susceptible to respiratory syncytial virus infection.

    Science.gov (United States)

    Glasser, Stephan W; Witt, Teah L; Senft, Albert P; Baatz, John E; Folger, Dusti; Maxfield, Melissa D; Akinbi, Henry T; Newton, Danforth A; Prows, Daniel R; Korfhagen, Thomas R

    2009-07-01

    Patients with mutations in the pulmonary surfactant protein C (SP-C) gene develop interstitial lung disease and pulmonary exacerbations associated with viral infections including respiratory syncytial virus (RSV). Pulmonary infection with RSV caused more severe interstitial thickening, air space consolidation, and goblet cell hyperplasia in SP-C-deficient (Sftpc(-/-)) mice compared with SP-C replete mice. The RSV-induced pathology resolved more slowly in Sftpc(-/-) mice with lung inflammation persistent up to 30 days postinfection. Polymorphonuclear leukocyte and macrophage counts were increased in the bronchoalveolar lavage (BAL) fluid of Sftpc(-/-) mice. Viral titers and viral F and G protein mRNA were significantly increased in both Sftpc(-/-) and heterozygous Sftpc(+/-) mice compared with controls. Expression of Toll-like receptor 3 (TLR3) mRNA was increased in the lungs of Sftpc(-/-) mice relative to Sftpc(+/+) mice before and after RSV infection. Consistent with the increased TLR3 expression, BAL inflammatory cells were increased in the Sftpc(-/-) mice after exposure to a TLR3-specific ligand, poly(I:C). Preparations of purified SP-C and synthetic phospholipids blocked poly(I:C)-induced TLR3 signaling in vitro. SP-C deficiency increases the severity of RSV-induced pulmonary inflammation through regulation of TLR3 signaling. PMID:19304906

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  20. Pulmonary surfactant and lung transplantation

    OpenAIRE

    Erasmus, Michiel Elardus

    1997-01-01

    Pulmonary surfactant lowers the surface tension at the air-water interface inside the alveolus. This is achieved by adsorption of surfactant phospholipids at the air-water interface, a process controlled by surfactant-associated proteins, such as SP-A. In this way, surfactant prevents collapse of the alveolus at end expiration, prevents formation of alveolar edema and increases the compliance of the lung. In chapter 1a an overview is given how the normal function of surfactant can be affected...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    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...

  2. Exposure of surfactant protein A to ozone in vitro and in vivo impairs its interactions with alveolar cells

    Energy Technology Data Exchange (ETDEWEB)

    Oosting, R.S.; Van Iwaarden, J.F.; Van Bree, L.; Verhoef, J.; Van Golde, L.M.; Haagsman, H.P. (Laboratory of Veterinary Biochemistry, Utrecht University (Netherlands))

    1992-01-01

    This study focused on the question of whether exposure of surfactant protein A (SP-A) to ozone affected properties of this protein that may be involved in regulating alveolar type II cell and alveolar macrophage functions. In vitro exposure of human or canine SP-A to ozone reduced the ability of this protein to inhibit phorbol-ester induced secretion of (3H)phosphatidylcholine by alveolar type II cells in culture. Ozone-exposed human SP-A showed a decreased ability to enhance phagocytosis of herpes simplex virus and to stimulate superoxide anion production by alveolar macrophages. Experiments with elastase showed that ozone-exposed canine SP-A was more susceptible to proteolysis. A conformational change of the protein could underlie this phenomenon. Surfactant isolated from ozone-exposed rats (0.4 ppm ozone for 12 h) was also less able to stimulate superoxide anion production by alveolar macrophages than surfactant from control rats, which suggested that SP-A in vivo was also susceptible to ozone. The results of this study suggest that SP-A-alveolar cell interactions can be inhibited by ozone exposure, which may contribute to the toxicity of ozone in the lungs.

  3. The Pulmonary Surfactant: Impact of Tobacco Smoke and Related Compounds on Surfactant and Lung Development

    Directory of Open Access Journals (Sweden)

    Scott J Elliott

    2004-03-01

    Full Text Available Abstract Cigarette smoking, one of the most pervasive habits in society, presents many well established health risks. While lung cancer is probably the most common and well documented disease associated with tobacco exposure, it is becoming clear from recent research that many other diseases are causally related to smoking. Whether from direct smoking or inhaling environmental tobacco smoke (ETS, termed secondhand smoke, the cells of the respiratory tissues and the lining pulmonary surfactant are the first body tissues to be directly exposed to the many thousands of toxic chemicals in tobacco. Considering the vast surface area of the lung and the extreme attenuation of the blood-air barrier, it is not surprising that this organ is the primary route for exposure, not just to smoke but to most environmental contaminants. Recent research has shown that the pulmonary surfactant, a complex mixture of phospholipids and proteins, is the first site of defense against particulates or gas components of smoke. However, it is not clear what effect smoke has on the surfactant. Most studies have demonstrated that smoking reduces bronchoalveolar lavage phospholipid levels. Some components of smoke also appear to have a direct detergent-like effect on the surfactant while others appear to alter cycling or secretion. Ultimately these effects are reflected in changes in the dynamics of the surfactant system and, clinically in changes in lung mechanics. Similarly, exposure of the developing fetal lung through maternal smoking results in postnatal alterations in lung mechanics and higher incidents of wheezing and coughing. Direct exposure of developing lung to nicotine induces changes suggestive of fetal stress. Furthermore, identification of nicotinic receptors in fetal lung airways and corresponding increases in airway connective tissue support a possible involvement of nicotine in postnatal asthma development. Finally, at the level of the alveoli of the lung

  4. 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;

    2006-01-01

    Surfactant protein D (SP-D) is a collectin that plays an important role in the innate immune system and takes part in the surfactant homeostasis by regulating the surfactant pool size. The aims of this study were to investigate the values of SP-D in umbilical cord blood and capillary blood of...... premature infants and to relate the levels to perinatal conditions. A total of 254 premature infants were enrolled in the present study. Umbilical cord blood was drawn at the time of birth and capillary blood at regular intervals throughout the admission. The concentration of SP-D in umbilical cord blood...... concentration 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...

  5. Dynamic changes in expression of clara cell protein and surfactant protein-D expressions in lung tissues and bronchaoalveolar lavage fluid of silica-treated rats

    Institute of Scientific and Technical Information of China (English)

    张海鹏

    2014-01-01

    Objective To investigate the dynamic changes in the expression of clara cell protein(CC16)and surfactant protein D(SP-D)in the lung tissues and bronchoalveolar lavage fluid(BALF)of silicatreated rats.Methods Eighty-four Wistar rats were randomly divided into control group(n=42)and silica group(n=42).The silica group was subsequently divided into 3,7,14,21,28,

  6. Plasma levels of surfactant protein D and KL-6 for evaluation of lung injury in critically ill mechanically ventilated patients

    OpenAIRE

    Slutsky Arthur S; Zhang Haibo; Haitsma Jack J; Royakkers Annick ANM; Determann Rogier M; Ranieri V Marco; Schultz Marcus J

    2010-01-01

    Abstract Background Preventing ventilator-associated lung injury (VALI) has become pivotal in mechanical ventilation of patients with acute lung injury (ALI) or its more severe form, acute respiratory distress syndrome (ARDS). In the present study we investigated whether plasma levels of lung-specific biological markers can be used to evaluate lung injury in patients with ALI/ARDS and patients without lung injury at onset of mechanical ventilation. Methods Plasma levels of surfactant protein ...

  7. Surfactant Protein D as a Novel Therapy for Periventricular Leukomalacia: Is It the Missing Piece of the Puzzle?

    OpenAIRE

    Engür, Defne; Kumral, Abdullah

    2012-01-01

    Activation of microglia with an inflammatory insult, which plays a central role in periventricular leukomalacia (PVL), results in premyelinating oligodendrocyte death via release of certain cytokines, reactive oxygen and nitrogen species. Toll-like receptor (TLR) 4 is necessary for lipopolysaccharide (LPS) induced oligodenrocyte injury in the CNS. Having an ability to bind TLR 2, 4, and LPS receptor CD14, surfactant protein D (spD) may be a promising agent to counteract the pathways associate...

  8. Circulating surfactant protein D is associated to mortality in elderly women

    DEFF Research Database (Denmark)

    Johansson, Helle Wulf; Thinggaard, M.; Tan, Q.;

    2013-01-01

    BACKGROUND: Surfactant protein D (SP-D) is produced in the lungs and additional mucosal surfaces. Systemic SP-D levels are previously associated to aging-related- and lifestyle-related disorders and predicts mortality in cardiovascular and lung diseases. However, the association between higher...... investigated after a 13-year follow-up period. Survival analysis showed that increasing quartiles of serum SP-D levels were associated to mortality in 70+ year old women (hazard ratio [HR], 1.29; 95% confidence interval [CI], 0.93-1.78; p=0.032) adjusted for age, smoking and BMI. Women with SP-D levels above...... 2100ng/ml had significantly increased mortality when compared to elderly women with SP-D levels equal to or below 2100ng/ml (HR, 1.45; 95% CI, 1.12-1.88; p=0.005). The likelihood that the female twin with the highest SP-D level died first increased with increasing SP-D levels (p=0.031) - that is, the...

  9. Surfactant Protein-D Is Essential for Immunity to Helminth Infection.

    Directory of Open Access Journals (Sweden)

    Sumaiyya Thawer

    2016-02-01

    Full Text Available Pulmonary epithelial cell responses can enhance type 2 immunity and contribute to control of nematode infections. An important epithelial product is the collectin Surfactant Protein D (SP-D. We found that SP-D concentrations increased in the lung following Nippostrongylus brasiliensis infection; this increase was dependent on key components of the type 2 immune response. We carried out loss and gain of function studies of SP-D to establish if SP-D was required for optimal immunity to the parasite. N. brasiliensis infection of SP-D-/- mice resulted in profound impairment of host innate immunity and ability to resolve infection. Raising pulmonary SP-D levels prior to infection enhanced parasite expulsion and type 2 immune responses, including increased numbers of IL-13 producing type 2 innate lymphoid cells (ILC2, elevated expression of markers of alternative activation by alveolar macrophages (alvM and increased production of the type 2 cytokines IL-4 and IL-13. Adoptive transfer of alvM from SP-D-treated parasite infected mice into naïve recipients enhanced immunity to N. brasiliensis. Protection was associated with selective binding by the SP-D carbohydrate recognition domain (CRD to L4 parasites to enhance their killing by alvM. These findings are the first demonstration that the collectin SP-D is an essential component of host innate immunity to helminths.

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

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    Bracken Michael B

    2006-08-01

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

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

    Science.gov (United States)

    Nejati Moshtaghin, Mahboubeh

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

  12. Critical structural and functional roles for the N-terminal insertion sequence in surfactant protein B analogs.

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    Frans J Walther

    Full Text Available BACKGROUND: Surfactant protein B (SP-B; 79 residues belongs to the saposin protein superfamily, and plays functional roles in lung surfactant. The disulfide cross-linked, N- and C-terminal domains of SP-B have been theoretically predicted to fold as charged, amphipathic helices, suggesting their participation in surfactant activities. Earlier structural studies with Mini-B, a disulfide-linked construct based on the N- and C-terminal regions of SP-B (i.e., approximately residues 8-25 and 63-78, confirmed that these neighboring domains are helical; moreover, Mini-B retains critical in vitro and in vivo surfactant functions of the native protein. Here, we perform similar analyses on a Super Mini-B construct that has native SP-B residues (1-7 attached to the N-terminus of Mini-B, to test whether the N-terminal sequence is also involved in surfactant activity. METHODOLOGY/RESULTS: FTIR spectra of Mini-B and Super Mini-B in either lipids or lipid-mimics indicated that these peptides share similar conformations, with primary alpha-helix and secondary beta-sheet and loop-turns. Gel electrophoresis demonstrated that Super Mini-B was dimeric in SDS detergent-polyacrylamide, while Mini-B was monomeric. Surface plasmon resonance (SPR, predictive aggregation algorithms, and molecular dynamics (MD and docking simulations further suggested a preliminary model for dimeric Super Mini-B, in which monomers self-associate to form a dimer peptide with a "saposin-like" fold. Similar to native SP-B, both Mini-B and Super Mini-B exhibit in vitro activity with spread films showing near-zero minimum surface tension during cycling using captive bubble surfactometry. In vivo, Super Mini-B demonstrates oxygenation and dynamic compliance that are greater than Mini-B and compare favorably to full-length SP-B. CONCLUSION: Super Mini-B shows enhanced surfactant activity, probably due to the self-assembly of monomer peptide into dimer Super Mini-B that mimics the functions and

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

    Science.gov (United States)

    AKIKI, ZEINA; FAKIH, DALIA; JOUNBLAT, RANIA; CHAMAT, SOULAIMA; WAKED, MIRNA; HOLMSKOV, UFFE; SORENSEN, GRITH L.; NADIF, RACHEL; SALAMEH, PASCALE

    2016-01-01

    Biological markers can help to better identify a disease or refine its diagnosis. In the present study, the association between surfactant protein D (SP-D) and chronic obstructive pulmonary disease (COPD) was studied among subjects consulting for respiratory diseases or symptoms and was compared with C-reactive protein (CRP) and fibrinogen. A further aim of this study was to identify the optimal cut-off point of SP-D able to discriminate COPD patients. A case-control study including 90 COPD patients, 124 asthma patients and 180 controls was conducted. Standardized questionnaires were administered and lung function tests were performed. Biological markers were measured in blood samples according to standardized procedures. The association between SP-D and COPD was investigated using logistic regression models. Receiver-operating characteristic curves were used for threshold identification. SP-D levels above the median value were positively associated with COPD [adjusted odds ratio (OR)=3.86, 95% confidence interval (CI): 1.51–9.85, P=0.005). No associations with COPD or asthma were found for CRP or fibrinogen levels. Scores for COPD diagnosis in all COPD patients or ever-smoker COPD patients were identified (sensitivity, 76.4 and 77.8%; specificity, 89.3 and 88.5%, respectively). The results indicate that SP-D can differentiate COPD from other respiratory symptoms or diseases. Used with socio-demographic characteristics and respiratory symptoms, SP-D is able to discriminate COPD patients from controls, particularly among smokers. PMID:26997985

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

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    Chang-Jiang Guo

    2008-11-01

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

  15. Alveolar type II cells express a high-affinity receptor for pulmonary surfactant protein A

    International Nuclear Information System (INIS)

    Primary cultures of rat alveolar type II cells bind radiolabeled pulmonary surfactant protein A (SP-A) with high affinity. The binding of 125I-labeled SP-A is time- and temperature-dependent and is not accompanied by significant degradation. The binding process is saturable at low concentrations of SP-A, and unlabeled SP-A readily competes with labeled SP-A for cellular binding sites. Subsequent to binding, two pools of cell-associated 125I-labeled SP-A can be identified based upon sensitivity to trypsin at 0 degree C. It is likely that the trypsin-sensitive pool comprises 125I-labeled SP-A bound to the cell surface and the trypsin-insensitive pool comprises the internalized protein. Scatchard analysis of cell surface binding of SP-A at 0.1-10 μg/ml shows positive cooperativity at concentrations between 0.1 and 1 μg/ml. Hill plots give nH = 1.34 ± 0.08 with an apparent dissociation constant K'd = 1.02 ± 0.32 μg/ml. The binding of SP-A to type II cells shows an absolute requirement for Ca2+. The putative receptor for SP-A is unaffected by treatment of type II cells with a variety of proteases and N-Glycanase. Alveolar macrophages also exhibit high-affinity binding of SP-A, but rat lung fibroblasts and the alveolar epithelial cell line L2 exhibit only nonspecific binding

  16. Purifying selection drives the evolution of surfactant protein C (SP-C) independently of body temperature regulation in mammals.

    Science.gov (United States)

    Potter, Sally; Orgeig, Sandra; Donnellan, Stephen; Daniels, Christopher B

    2007-06-01

    The pulmonary surfactant system of heterothermic mammals must be capable of dealing with the effect of low body temperatures on the physical state of the lipid components. We have shown previously that there is a modest increase in surfactant cholesterol during periods of torpor, however these changes do not fully explain the capacity of surfactant to function under the wide range of physical conditions imposed by torpor. Here we examine indirectly the role of surfactant protein C (SP-C) in adapting to variable body temperatures by testing for the presence of positive (adaptive) selection during evolutionary transitions between heterothermy and homeothermy. We sequenced SP-C from genomic DNA of 32 mammalian species from groups of closely related heterothermic and homeothermic species (contrasts). We used phylogenetic analysis by maximum likelihood estimates of rates of non-synonymous to synonymous substitutions and fully Bayesian inference of these sequences to determine whether the mode of body temperature regulation exerts a selection pressure driving the molecular adaptation of SP-C. The protein sequence of SP-C is highly conserved with synonymous or highly conservative amino acid substitutions being predominant. The evolution of SP-C among mammals is characterised by high codon usage bias and high rates of transition/transversion. The only contrast to show evidence of positive selection was that of the bears (Ursus americanus and U. maritimus). The significance of this result is unclear. We show that SP-C is under strong evolutionary constraints, driven by purifying selection, presumably to maintain protein function despite variation in the mode of body temperature regulation. PMID:20483290

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-08-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...

  19. Ranaspumin-2: Structure and Function of a Surfactant Protein from the Foam Nests of a Tropical Frog

    OpenAIRE

    Mackenzie, Cameron D.; Smith, Brian O; Meister, Annette; Blume, Alfred; Zhao, Xiubo; Jian R Lu; Kennedy, Malcolm W.; Cooper, Alan

    2009-01-01

    Ranaspumin-2 (Rsn-2) is a monomeric, 11 kDa surfactant protein identified as one of the major foam nest components of the túngara frog (Engystomops pustulosus), with an amino acid sequence unlike any other protein described so far. We report here on its structure in solution as determined by high-resolution NMR analysis, together with investigations of its conformation and packing at the air-water interface using a combination of infrared and neutron reflectivity techniques. Despite the lack ...

  20. Budesonide/formoterol enhances the expression of pro Surfactant Protein-B in lungs of COPD patients.

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    Soo Jung Um

    Full Text Available RATIONALE & AIM: Pulmonary surfactants are essential components of lung homeostasis. In chronic obstructive pulmonary disease (COPD, surfactant expression decreases in lungs whereas, there is a paradoxical increase in protein expression in plasma. The latter has been associated with poor health outcomes in COPD. The purpose of this study was to determine the relationship of surfactants and other pneumoproteins in bronchoalveolar lavage (BAL fluid and plasma to airflow limitation and the effects of budesonide/formoterol on this relationship. METHODS: We recruited (clinical trials.gov identifier: NCT00569712 7 smokers without COPD and 30 ex and current smokers with COPD who were free of exacerbations for at least 4 weeks. All subjects were treated with budesonide/formoterol 400/12 µg twice a day for 4 weeks. BAL fluid and plasma samples were obtained at baseline and the end of the 4 weeks. We measured lung-predominant pneumoproteins: pro-Surfactant Protein-B (pro-SFTPB, Surfactant Protein-D (SP-D, Club Cell Secretory Protein-16 (CCSP-16 and Pulmonary and Activation-Regulated Chemokine (PARC/CCL-18 in BAL fluid and plasma. RESULTS: BAL Pro-SFTPB concentrations had the strongest relationship with airflow limitation as measured by FEV1/FVC (Spearman rho=0.509; p=0.001 and FEV1% of predicted (Spearman rho= 0.362; p=0.028. Plasma CCSP-16 concentrations were also significantly related to airflow limitation (Spearman rho=0.362; p=0.028 for FEV1% of predicted. The other biomarkers in BAL fluid or plasma were not significantly associated with airflow limitation. In COPD subjects, budesonide/formoterol significantly increased the BAL concentrations of pro-SFTPB by a median of 62.46 ng/ml (p=0.022 or 48.7% from baseline median value. CONCLUSION: Increased severity of COPD is associated with reduced Pro-SFTPB levels in BAL fluid. Short-term treatment with budesonide/formoterol increases these levels in BAL fluid. Long term studies will be needed to determine

  1. Crystallization and preliminary X-ray diffraction of the surfactant protein Lv-ranaspumin from the frog Leptodactylus vastus

    International Nuclear Information System (INIS)

    The purification, crystallization and MS analysis of a natural surfactant protein from the frog L. vastus are described. Lv-ranaspumin is a natural surfactant protein with a molecular mass of 23.5 kDa which was isolated from the foam nest of the frog Leptodactylus vastus. Only a partial amino-acid sequence is available for this protein and it shows it to be distinct from any protein sequence reported to date. The protein was purified from the natural source by ion-exchange and size-exclusion chromatography and was crystallized by sitting-drop vapour diffusion using the PEG/Ion screen at 293 K. A complete data set was collected to 3.5 Å resolution. The crystal belonged to the orthorhombic space group P212121, with unit-cell parameters a = 51.96, b = 89.99, c = 106.00 Å. Assuming the presence of two molecules in the asymmetric unit, the solvent content was estimated to be 54%

  2. Innate immunity of surfactant proteins A and D in urinary tract infection with uropathogenic Escherichia coli.

    Science.gov (United States)

    Hu, Fengqi; Ding, Guohua; Zhang, Zhiyong; Gatto, Louis A; Hawgood, Samuel; Poulain, Francis R; Cooney, Robert N; Wang, Guirong

    2016-01-01

    To investigate the effects of surfactant proteins A and D (SP-A and SP-D, respectively) in urinary tract infection (UTI), SP-A and SP-D double knockout (SP-A/D KO) and wild type (WT) C57BL/6 female mice were infected with uropathogenic Escherichia coli by intravesical inoculation. Compared with WT mice SP-A/D KO mice showed increased susceptibility to UTI, as evidenced by higher bacterial CFU, more infiltrating neutrophils and severe pathological changes. Keratinocyte-derived chemokine increased in the kidney of WT mice but not in SP-A/D KO mice 24 h post-infection. Compared with control, the level of IL-17 was elevated in the kidney of infected WT and SP-A/D KO mice and the level of IL-17 was higher in the infected SP-A/D KO mice than in infected WT mice 24 and 48 h post-infection. The basal level of p38 MAPK phosphorylation in SP-A/D KO mice was higher than in WT mice. The phosphorylated p38 level was elevated in the kidney of WT mice post infection but not in SP-A/D KO mice. Furthermore, in vitro growth of uropathogenic E. coli was inhibited by SP-A and SP-D. We conclude that SP-A and SP-D function as mediators of innate immunity by inhibiting bacterial growth and modulating renal inflammation in part by regulating p38 MAPK-related pathway in murine UTI. PMID:26511057

  3. Surfactant-derived proteins as markers of alveolar membrane damage in heart failure.

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    Paola Gargiulo

    Full Text Available In heart failure (HF alveolar-capillary membrane is abnormal. Surfactant-derived proteins (SPs and plasma receptor for advanced-glycation-end-products (RAGE have been proposed as lung damage markers.Eighty-nine chronic HF and 17 healthy subjects were evaluated by echocardiography, blood parameters, carbon monoxide lung diffusion (DLCO and cardiopulmonary exercise test. We measured immature SP-B, mature SP-B, SP-A, SP-D and RAGE plasma levels.Immature SP-B (arbitrary units, mature SP-A (ng/ml and SP-D (ng/ml, but not mature SP-B (ng/ml and RAGE (pg/ml levels, were higher in HF than in controls [immature SP-B: 15.6 (13.1, 75th-25th interquartile range Vs. 11.1 (6.4, p<0.01; SP-A, 29.6 (20.1 Vs. 18.3 (13.5, p = 0.01; SP-D: 125 (90 Vs. 78 (58, p<0.01]. Immature SP-B, SP-A, SP-D and RAGE values were related to DLCO, peak oxygen consumption, ventilatory efficiency, and brain natriuretic peptide (BNP, whereas plasma mature SP-B was not. The DLCO Vs. immature SP-B correlation was the strongest one. At multivariate analysis, RAGE was associated to age and creatinine, SP-A to DLCO and BNP, SP-D to BNP, mature SP-B to DLCO and creatinine, and immature SP-B only but strongly to DLCO.Immature SP-B is the most reliable biological marker of alveolar-capillary membrane function in HF.

  4. Respiratory symptoms among infants at risk for asthma: association with surfactant protein A haplotypes

    Directory of Open Access Journals (Sweden)

    Bracken Michael B

    2007-04-01

    Full Text Available Abstract Background We examined the association between single nucleotide polymorphisms (SNPs in loci encoding surfactant protein A (SFTPA and risk of wheeze and persistent cough during the first year of life among a cohort of infants at risk for developing asthma. Methods Between September 1996 and December 1998, mothers of newborn infants were invited to participate if they had an older child with clinician-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. Due to the association of SFTPA polymorphisms and race/ethnicity, analyses were restricted to 221 white infants for whom whole blood and respiratory data were available. Ordered logistic regression models were used to examine the association between respiratory symptom frequency and SFTPA haplotypes. Results The 6A allele haplotype of SFTPA1, with an estimated frequency of 6% among our study infants, was associated with an increased risk of persistent cough (OR 3.69, 95% CI 1.71, 7.98 and wheeze (OR 4.72, 95% CI 2.20, 10.11. The 6A/1A haplotype of SFTPA, found among approximately 5% of the infants, was associated with an increased risk of persistent cough (OR 3.20, 95% CI 1.39, 7.36 and wheeze (OR 3.25, 95% CI 1.43, 7.37. Conclusion Polymorphisms within SFTPA loci may be associated with wheeze and persistent cough in white infants at risk for asthma. These associations require replication and exploration in other ethnic/racial groups.

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    P.P.R. Lyra

    2011-01-01

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

  7. Surfactant protein (SP-A suppresses preterm delivery and inflammation via TLR2.

    Directory of Open Access Journals (Sweden)

    Varkha Agrawal

    Full Text Available Toll like receptors (TLRs are pattern-recognition molecules that initiate the innate immune response to pathogens. Pulmonary surfactant protein (SP-A is an endogenously produced ligand for TLR2 and TLR4. SP-A has been proposed as a fetally produced signal for the onset of parturition in the mouse. We examined the effect of interactions between SP-A and the pathogenic TLR agonists lipopolysaccharide (LPS, peptidoglycan (PGN and polyinosinic:cytidylic acid (poly(I:C (ligands for TLR4, TLR2 and TLR3, respectively on the expression of inflammatory mediators and preterm delivery. Three types of mouse macrophages (the cell line RAW 264.7, and fresh amniotic fluid and peritoneal macrophages, including macrophages from TLR4 and TLR2 knockout mice were treated for up to 7 hours with pathogenic TLR agonists with or without SP-A. SP-A alone had no effect upon inflammatory mediators in mouse macrophages and did not independently induce preterm labor. SP-A significantly suppressed TLR ligand-induced expression of inflammatory mediators (interleukin (IL-1β, tumor necrosis factor (TNF-α and the chemokine CCL5 via a TLR2 dependent mechanism. In a mouse inflammation-induced preterm delivery model, intrauterine administration of SP-A significantly inhibited preterm delivery, suppressed the expression of proinflammatory mediators and enhanced the expression of the CXCL1 and anti-inflammatory mediator IL-10. We conclude that SP-A acts via TLR2 to suppress TLR ligand-induced preterm delivery and inflammatory responses.

  8. 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.

  9. POLYMERIC SURFACTANT STRUCTURE

    Institute of Scientific and Technical Information of China (English)

    P.M. Saville; J.W. White

    2001-01-01

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

  10. Anionic Pulmonary Surfactant Phospholipids Inhibit Inflammatory Responses from Alveolar Macrophages and U937 Cells by Binding the Lipopolysaccharide-interacting Proteins CD14 and MD-2*♦

    OpenAIRE

    Kuronuma, Koji; Mitsuzawa, Hiroaki; Takeda, Katsuyuki; Nishitani, Chiaki; Chan, Edward D.; Kuroki, Yoshio; Nakamura, Mari; Voelker, Dennis R.

    2009-01-01

    Lipopolysaccharide (LPS), derived from Gram-negative bacteria, is a major cause of acute lung injury and respiratory distress syndrome. Pulmonary surfactant is secreted as a complex mixture of lipids and proteins onto the alveolar surface of the lung. Surfactant phospholipids are essential in reducing surface tension at the air-liquid interface and preventing alveolar collapse at the end of the respiratory cycle. In the present study, we determined that palmitoyl-oleoyl-phosphatidylglycerol a...

  11. Expression of p53 protein, Jaagsiekte sheep retrovirus matrix protein, and surfactant protein in the lungs of sheep with pulmonary adenomatosis.

    Science.gov (United States)

    İlhan, Fatma; Vural, Sevil A; Yıldırım, Serkan; Sözdutmaz, İbrahim; Alcigir, Mehmet E

    2016-05-01

    Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring cancer in sheep that is caused by the Jaagsiekte sheep retrovirus (JSRV). Because the pathologic and epidemiologic features of OPA are similar to those of bronchoalveolar carcinoma in humans, OPA is considered a useful animal model for pulmonary carcinogenesis. In this study, 3,512 lungs from various breeds of sheep were collected and macroscopically examined. OPA was identified in 30 sheep, and samples of these animals were further examined by histologic, immunohistochemical (p53 protein, surfactant protein A [SP-A], proliferating cell nuclear antigen [PCNA], JSRV matrix protein [MA]), and PCR methods. Papillary or acinar adenocarcinomas were detected microscopically in the affected areas. Immunoreactivity for p53 PAb240 was detected in 13 sheep, whereas p53 DO-1 was not detected in any of the OPA animals. PCNA immunoreactivity was recorded in 27 animals. SP-A and JSRV MA protein was immunopositive in all 30. JSRV proviral DNA was detected by PCR analysis in all of the lung samples collected from OPA animals. In addition, the pulmonary SP-A levels were increased in tumor cells. The results of this study suggest that PCNA and p53 protein expression may be useful indicators in monitoring malignancy of pulmonary tumors. PMID:27016721

  12. Non Invasive Surfactant Application

    Directory of Open Access Journals (Sweden)

    Hacer Yapicioglu

    2013-08-01

    Full Text Available Surfactant replacement therapy has been the mainstay of treatment for preterm infants with respiratory distress syndrome for more than twenty years. In recent years, the growing interest in noninvasive ventilation has led to novel approaches of administration. Non-invasive techniques of respiratory support were developed in order to reduce the adverse effects associated with ventilation via an endotracheal tube. Noninvasive surfactant administration technique during spontaneous breathing along with nasal continous positive airway pressure support successfully reduces the need for further respiratory support and bronchopulmonary dysplasia rate in very low birth weight infants. Here we reviewed the new approches ton surfactant administration. [Archives Medical Review Journal 2013; 22(4.000: 634-644

  13. The Wurst protein: A novel endocytosis regulator involved in airway clearance and respiratory tube size control

    OpenAIRE

    Wingen, Christian; Aschenbrenner, Anna C; Stümpges, Birgit; Hoch, Michael; Behr, Matthias

    2009-01-01

    The mammalian lung and the Drosophila airways are composed of an intricate network of epithelial tubes that transports fluids or gases and converts during late embryogenesis from liquid- to air-filling. Conserved growth factor pathways have been characterized in model organisms such as Drosophila or the mouse that control patterning and branching of tubular networks. In contrast, knowledge of the coordination of respiratory tube size and physiology is still limited. Latest studies have shown ...

  14. Surfactant protein C peptides with salt-bridges (“ion-locks” promote high surfactant activities by mimicking the α-helix and membrane topography of the native protein

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    Frans J. Walther

    2014-07-01

    Full Text Available Background. Surfactant protein C (SP-C; 35 residues in lungs has a cationic N-terminal domain with two cysteines covalently linked to palmitoyls and a C-terminal region enriched in Val, Leu and Ile. Native SP-C shows high surface activity, due to SP-C inserting in the bilayer with its cationic N-terminus binding to the polar headgroup and its hydrophobic C-terminus embedded as a tilted, transmembrane α-helix. The palmitoylcysteines in SP-C act as ‘helical adjuvants’ to maintain activity by overriding the β-sheet propensities of the native sequences. Objective. We studied SP-C peptides lacking palmitoyls, but containing glutamate and lysine at 4-residue intervals, to assess whether SP-C peptides with salt-bridges (“ion-locks” promote surface activity by mimicking the α-helix and membrane topography of native SP-C. Methods. SP-C mimics were synthesized that reproduce native sequences, but without palmitoyls (i.e., SP-Css or SP-Cff, with serines or phenylalanines replacing the two cysteines. Ion-lock SP-C molecules were prepared by incorporating single or double Glu−–Lys+ into the parent SP-C’s. The secondary structures of SP-C mimics were studied with Fourier transform infrared (FTIR spectroscopy and PASTA, an algorithm that predicts β-sheet propensities based on the energies of the various β-sheet pairings. The membrane topography of SP-C mimics was investigated with orientated and hydrogen/deuterium (H/D exchange FTIR, and also Membrane Protein Explorer (MPEx hydropathy analysis. In vitro surface activity was determined using adsorption surface pressure isotherms and captive bubble surfactometry, and in vivo surface activity from lung function measures in a rabbit model of surfactant deficiency. Results. PASTA calculations predicted that the SP-Css and SP-Cff peptides should each form parallel β-sheet aggregates, with FTIR spectroscopy confirming high parallel β-sheet with ‘amyloid-like’ properties. The enhanced

  15. Macrophage Dysfunction and Susceptibility to Pulmonary Pseudomonas aeruginosa Infection in Surfactant Protein C-Deficient Mice1

    OpenAIRE

    Glasser, Stephan W.; Senft, Albert P; Jeffrey A Whitsett; Melissa D. Maxfield; Ross, Gary F.; Richardson, Theresa R.; Prows, Daniel R.; Xu, Yan; Korfhagen, Thomas R.

    2008-01-01

    To determine the role of surfactant protein C (SP-C) in host defense, SP-C-deficient (Sftpc−/−) mice were infected with the pulmonary pathogen Pseudomonas aeruginosa by intratracheal injection. Survival of young, postnatal day 14 Sftpc−/−ice was decreased in comparison to Sftpc+/+ mice. The sensitivity to Pseudomonas bacteria was specific to the 129S6 strain of Sftpc−/− mice, a strain that spontaneously develops interstitial lung disease-like lung pathology with age. Pulmonary bacterial load ...

  16. Circulating surfactant protein -D is low and correlates negatively with systemic inflammation in early, untreated rheumatoid arthritis

    DEFF Research Database (Denmark)

    Christensen, Anne Friesgaard; Sørensen, Grith Lykke; Hørslev-Petersen, Kim; Holmskov, Uffe; Lindegaard, Hanne Merete; Junker, Kirsten; Hetland, Merete Lund; Stengaard-Pedersen, Kristian; Jacobsen, Søren; Lottenburger, Tine; Ellingsen, Torkell; Andersen, Lis Smedegaard; Hansen, Ib; Skjødt, Henrik; Pedersen, Jens Kristian; Lauridsen, Ulrik Birk; Svendsen, Anders; Tarp, Ulrik; Pødenphant, Jan; Vestergaard, Aage; Jurik, Anne Grethe; Østergaard, Mikkel; Junker, Peter

    2010-01-01

    Surfactant protein D (SP-D) is a collectin with immuno-regulatory functions, which may depend on oligomerization. Anti-microbial and anti-inflammatory properties have been attributed to multimeric SP-D variants, while trimeric subunits per se have been suggested to enhance inflammation. Previously......, we reported low circulating SP-D in early rheumatoid arthritis (RA), and the present investigation aims to extend these data by serial SP-D serum measurements, studies on synovial fluid, SP-D size distribution and genotyping in patients with early RA....

  17. Adsorption and transport of surfactant/protein onto a foam lamella within a foam fractionation column with reflux

    OpenAIRE

    Vitasari, Denny

    2014-01-01

    Foam fractionation is an economical and environmentally friendly separation method for surface active material using a rising column of foam. The system of foam fractionation column with reflux is selected since such a system can improve the enrichment of the product collected from the top of the column. Due to the reflux, it is assumed that there is more surface active material (surfactant and/or protein) in the Plateau border than that in the foam lamella, so that the Plateau border acts as...

  18. Surfactant Protein-A as an Anti-Inflammatory Component in the Amnion: Implications for Human Pregnancy1

    OpenAIRE

    Lee, Deug-Chan; Romero, Roberto; Kim, Chong Jai; Chaiworapongsa, Tinnakorn; Tarca, Adi L.; Lee, JoonHo; Suh, Yeon-Lim; Mazaki-Tovi, Shali; Vaisbuch, Edi; Mittal, Pooja; Draghici, Sorin; Erez, Offer; Kusanovic, Juan Pedro; Hassan, Sonia S; Kim, Jung-Sun

    2010-01-01

    The mechanism of mouse parturition is thought to involve myometrial infiltration by amniotic fluid (AF) macrophages, activated by surfactant protein-A (SP-A). In humans, the concentration of AF SP-A decreases during labor, and no fetal macrophages are found in the myometrium after labor. Therefore, it appears that the mechanisms of labor in mice and humans are different. We investigated a potential role for SP-A in human pregnancy and parturition by examining SP-A expression patterns in AF an...

  19. G-protein-coupled estrogen receptor agonist suppresses airway inflammation in a mouse model of asthma through IL-10.

    Science.gov (United States)

    Itoga, Masamichi; Konno, Yasunori; Moritoki, Yuki; Saito, Yukiko; Ito, Wataru; Tamaki, Mami; Kobayashi, Yoshiki; Kayaba, Hiroyuki; Kikuchi, Yuta; Chihara, Junichi; Takeda, Masahide; Ueki, Shigeharu; Hirokawa, Makoto

    2015-01-01

    Estrogen influences the disease severity and sexual dimorphism in asthma, which is caused by complex mechanisms. Besides classical nuclear estrogen receptors (ERαβ), G-protein-coupled estrogen receptor (GPER) was recently established as an estrogen receptor on the cell membrane. Although GPER is associated with immunoregulatory functions of estrogen, the pathophysiological role of GPER in allergic inflammatory lung disease has not been examined. We investigated the effect of GPER-specific agonist G-1 in asthmatic mice. GPER expression in asthmatic lung was confirmed by immunofluorescent staining. OVA-sensitized BALB/c and C57BL/6 mice were treated with G-1 by daily subcutaneous injections during an airway challenge phase, followed by histological and biochemical examination. Strikingly, administration of G-1 attenuated airway hyperresponsiveness, accumulation of inflammatory cells, and levels of Th2 cytokines (IL-5 and IL-13) in BAL fluid. G-1 treatment also decreased serum levels of anti-OVA IgE antibodies. The frequency of splenic Foxp3+CD4+ regulatory T cells and IL-10-producing GPER+CD4+ T cells was significantly increased in G-1-treated mice. Additionally, splenocytes isolated from G-1-treated mice showed greater IL-10 production. G-1-induced amelioration of airway inflammation and IgE production were abolished in IL-10-deficient mice. Taken together, these results indicate that extended GPER activation negatively regulates the acute asthmatic condition by altering the IL-10-producing lymphocyte population. The current results have potential importance for understanding the mechanistic aspects of function of estrogen in allergic inflammatory response. PMID:25826377

  20. G-protein-coupled estrogen receptor agonist suppresses airway inflammation in a mouse model of asthma through IL-10.

    Directory of Open Access Journals (Sweden)

    Masamichi Itoga

    Full Text Available Estrogen influences the disease severity and sexual dimorphism in asthma, which is caused by complex mechanisms. Besides classical nuclear estrogen receptors (ERαβ, G-protein-coupled estrogen receptor (GPER was recently established as an estrogen receptor on the cell membrane. Although GPER is associated with immunoregulatory functions of estrogen, the pathophysiological role of GPER in allergic inflammatory lung disease has not been examined. We investigated the effect of GPER-specific agonist G-1 in asthmatic mice. GPER expression in asthmatic lung was confirmed by immunofluorescent staining. OVA-sensitized BALB/c and C57BL/6 mice were treated with G-1 by daily subcutaneous injections during an airway challenge phase, followed by histological and biochemical examination. Strikingly, administration of G-1 attenuated airway hyperresponsiveness, accumulation of inflammatory cells, and levels of Th2 cytokines (IL-5 and IL-13 in BAL fluid. G-1 treatment also decreased serum levels of anti-OVA IgE antibodies. The frequency of splenic Foxp3+CD4+ regulatory T cells and IL-10-producing GPER+CD4+ T cells was significantly increased in G-1-treated mice. Additionally, splenocytes isolated from G-1-treated mice showed greater IL-10 production. G-1-induced amelioration of airway inflammation and IgE production were abolished in IL-10-deficient mice. Taken together, these results indicate that extended GPER activation negatively regulates the acute asthmatic condition by altering the IL-10-producing lymphocyte population. The current results have potential importance for understanding the mechanistic aspects of function of estrogen in allergic inflammatory response.

  1. Effect of cysteine 85 on biochemical properties and biological function of human surfactant protein A variants.

    Science.gov (United States)

    Wang, Guirong; Myers, Catherine; Mikerov, Anatoly; Floros, Joanna

    2007-07-17

    Four "core" amino acid differences within the collagen-like domain distinguish the human surfactant protein A1 (SP-A1) variants from the SP-A2 variants. One of these, cysteine 85 that could form intermolecular disulfide bonds, is present in SP-A1 (Cys85) and absent in SP-A2 (Arg85). We hypothesized that residue 85 affects both the structure and function of SP-A1 and SP-A2 variants. To test this, wild-type (WT) variants, 6A2 of SP-A1 and 1A0 of SP-A2, and their mutants (6A2(C85R) and 1A0(R85C)) were generated and studied. We found the following: (1) Residue 85 affected the binding ability to mannose and the oligomerization pattern of SP-As. The 1A0(R85C) and 6A2(C85R) patterns were similar and/or resembled those of WT 6A2 and 1A0, respectively. (2) Both SP-A WT and mutants differentially induced rough LPS and Pseudomonas aeruginosa aggregation in the following order: 1A0 > 6A2 > 6A2(C85R) > 1A0(R85C) for Re-LPS aggregation and 1A0 > 6A2 = 6A2(C85R) = 1A0(R85C) for bacterial aggregation. (3) SP-A WT and mutants enhanced phagocytosis of P. aeruginosa by rat alveolar macrophages. Their phagocytic index order was 6A2(C85R) > 1A0 > 6A2 = 1A0(R85C). The activity of mutant 1A0(C85R) was significantly lower than WT 1A0 but similar to 6A2. Compared to WT 6A2, the 6A2(C85R) mutant exhibited a significantly higher activity. These results indicate that the SP-A variant/mutant with Arg85 exhibits a higher ability to enhance bacterial phagocytosis than that with Cys85. Residue 85 plays an important role in the structure and function of SP-A and is a major factor for the differences between SP-A1 and SP-A2 variants. PMID:17580966

  2. A novel nanobody specific for respiratory surfactant protein A has potential for lung targeting

    Directory of Open Access Journals (Sweden)

    Wang SM

    2015-04-01

    Full Text Available Shan-Mei Wang,1,* Xian He,2,* Nan Li,1,* Feng Yu,3 Yang Hu,1 Liu-Sheng Wang,1 Peng Zhang,4 Yu-Kui Du,1 Shan-Shan Du,1 Zhao-Fang Yin,1 Ya-Ru Wei,1 Xavier Mulet,5 Greg Coia,6 Dong Weng,1 Jian-Hua He,3 Min Wu,7 Hui-Ping Li1 1Department of Respiratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 2School of Medicine, Suzhou University, SuZhou, 3Shanghai Institute of Applied Physics, Chinese Academy of Sciences, 4Department of Chest Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 5CSIRO (Commonwealth Scientific and Industrial Research Materials Science and Engineering, Clayton, 6CSIRO Materials Science and Engineering, Parkville, Melbourne, VIC, Australia; 7Department of Basic Sciences, University of North Dakota, Grand Forks, ND, USA *These authors contributed equally to this work Abstract: Lung-targeting drugs are thought to be potential therapies of refractory lung diseases by maximizing local drug concentrations in the lung to avoid systemic circulation. However, a major limitation in developing lung-targeted drugs is the acquirement of lung-specific ligands. Pulmonary surfactant protein A (SPA is predominantly synthesized by type II alveolar epithelial cells, and may serve as a potential lung-targeting ligand. Here, we generated recombinant rat pulmonary SPA (rSPA as an antigen and immunized an alpaca to produce two nanobodies (the smallest naturally occurring antibodies specific for rSPA, designated Nb6 and Nb17. To assess these nanobodies’ potential for lung targeting, we evaluated their specificity to lung tissue and toxicity in mice. Using immunohistochemistry, we demonstrated that these anti-rSPA nanobodies selectively bound to rat lungs with high affinity. Furthermore, we intravenously injected fluorescein isothiocyanate-Nb17 in nude mice and observed its preferential accumulation in the lung to other tissues, suggesting high

  3. Surfactant therapy in late preterm infants

    Directory of Open Access Journals (Sweden)

    Murat Yurdakök

    2013-06-01

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

  4. Immunomodulatory Effects of Ambroxol on Airway Hyperresponsiveness and Inflammation

    Science.gov (United States)

    Miyahara, Nobuaki; Matsubara, Shigeki; Taube, Christian; Kitamura, Kenichi; Hirano, Astushi; Tanimoto, Mitsune; Gelfand, Erwin W.

    2016-01-01

    Ambroxol is used in COPD and asthma to increase mucociliary clearance and regulate surfactant levels, perhaps through anti-oxidant and anti-inflammatory activities. To determine the role and effect of ambroxol in an experimental model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) followed by 3 days of challenge. Airway hyperresponsiveness (AHR), lung cell composition and histology, and cytokine and protein carbonyl levels in bronchoalveolar lavage (BAL) fluid were determined. Ambroxol was administered either before the first OVA challenge or was begun after the last allergen challenge. Cytokine production levels from lung mononuclear cells (Lung MNCs) or alveolar macrophages (AM) were also determined. Administration of ambroxol prior to challenge suppressed AHR, airway eosinophilia, goblet cell metaplasia, and reduced inflammation in subepithelial regions. When given after challenge, AHR was suppressed but without effects on eosinophil numbers. Levels of IL-5 and IL-13 in BAL fluid were decreased when the drug was given prior to challenge; when given after challenge, increased levels of IL-10 and IL-12 were detected. Decreased levels of protein carbonyls were detected in BAL fluid following ambroxol treatment after challenge. In vitro, ambroxol increased levels of IL-10, IFN-γ, and IL-12 from Lung MNCs and AM, whereas IL-4, IL-5, and IL-13 production was not altered. Taken together, ambroxol was effective in preventing AHR and airway inflammation through upregulation of Th1 cytokines and protection from oxidative stress in the airways. PMID:27340385

  5. Genetic Disorders of Surfactant Dysfunction

    OpenAIRE

    Wert, Susan E.; Whitsett, Jeffrey A.; Nogee, Lawrence M.

    2009-01-01

    Mutations in the genes encoding the surfactant proteins B and C (SP-B and SP-C) and the phospholipid transporter, ABCA3, are associated with respiratory distress and interstitial lung disease in the pediatric population. Expression of these proteins is regulated developmentally, increasing with gestational age, and is critical for pulmonary surfactant function at birth. Pulmonary surfactant is a unique mixture of lipids and proteins that reduces surface tension at the air-liquid interface, pr...

  6. Surfactant-free purification of membrane protein complexes from bacteria: application to the staphylococcal penicillin-binding protein complex PBP2/PBP2a

    International Nuclear Information System (INIS)

    Surfactant-mediated removal of proteins from biomembranes invariably results in partial or complete loss of function and disassembly of multi-protein complexes. We determined the capacity of styrene-co-maleic acid (SMA) co-polymer to remove components of the cell division machinery from the membrane of drug-resistant staphylococcal cells. SMA-lipid nanoparticles solubilized FtsZ-PBP2-PBP2a complexes from intact cells, demonstrating the close physical proximity of these proteins within the lipid bilayer. Exposure of bacteria to (-)-epicatechin gallate, a polyphenolic agent that abolishes β-lactam resistance in staphylococci, disrupted the association between PBP2 and PBP2a. Thus, SMA purification provides a means to remove native integral membrane protein assemblages with minimal physical disruption and shows promise as a tool for the interrogation of molecular aspects of bacterial membrane protein structure and function. (paper)

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

    International Nuclear Information System (INIS)

    Highlights: → Treatment with Clonorchis sinensis-derived total protein attenuates OVA-induced airway inflammation and AHR to methacholine. → Induction of CD4+CD25+Foxp3+ T cells and IL-10 along with suppression of splenocyte proliferation by C. sinensis-derived total protein. → 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+CD25+Foxp3+ 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 relationship between the allergic immune response and

  8. Effect of surfactant protein A (SP-A) on the production of cytokines by human pulmonary macrophages.

    Science.gov (United States)

    Arias-Diaz, J; Garcia-Verdugo, I; Casals, C; Sanchez-Rico, N; Vara, E; Balibrea, J L

    2000-09-01

    Surfactant protein A (SP-A) is thought to play a role in the modulation of lung inflammation during acute respiratory distress syndrome (ARDS). However, SP-A has been reported both to stimulate and to inhibit the proinflammatory activity of pulmonary macrophages (Mphi). Because of the interspecies differences and heterogeneity of Mphi subpopulations used may have influenced previous controversial results, in this study, we investigated the effect of human SP-A on the production of cytokines and other inflammatory mediators by two well-defined subpopulations of human pulmonary Mphi. Surfactant and both alveolar (aMphi) and interstitial (iMphi) macrophages were obtained from multiple organ donor lungs by bronchoalveolar lavage and enzymatic digestion. Donors with either recent history of tobacco smoking, more than 72 h on mechanical ventilation, or any radiological pulmonary infiltrate were discarded. SP-A was purified from isolated surfactant using sequential butanol and octyl glucoside extractions. After 24-h preculture, purified Mphi were cultured for 24 h in the presence or absence of LPS (10 microg/mL), SP-A (50 microg/mL), and combinations. Nitric oxide and carbon monoxide (CO) generation (pmol/microg protein), cell cGMP content (pmol/microg protein), and tumor necrosis factor alpha (TNFalpha), interleukin (IL)-1, and IL-6 release to the medium (pg/microg protein) were determined. SP-A inhibited the lipopolysaccharide (LPS)-induced TNFalpha response of both interstitial and alveolar human Mphi, as well as the IL-1 response in iMphi. The SP-A effect on TNFalpha production could be mediated by a suppression in the LPS-induced increase in intracellular cGMP. In iMphi but not in aMphi, SP-A also inhibited the LPS-induced IL-1 secretion and CO generation. These data lend further credit to a physiological function of SP-A in regulating alveolar host defense and inflammation by suggesting a fundamental role of this apoprotein in limiting excessive proinflammatory

  9. Effects of the conjugation of whey proteins with gellan polysaccharides on surfactant-induced competitive displacement from the air-water interface.

    Science.gov (United States)

    Cai, B; Ikeda, S

    2016-08-01

    Whey proteins can be used to stabilize foams and emulsions against coalescence because of their ability to form viscoelastic films at the interface that resist film rupture on collision between colloidal particles. However, whey proteins are competitively displaced from the interface if small-molecule surfactants are added, leading to destabilization of the entire system. This is because surfactants are more effective in molecular packing at the interface, and they lower interfacial tension to a greater degree than whey proteins do, but their interfacial films are poor in viscoelasticity. We hypothesized that whey proteins would become more resistant to surfactant-induced competitive displacement if they were conjugated with network-forming polysaccharides. The protein moiety of the conjugate would be expected to enable its adsorption to the interface, and the polysaccharide moiety would be expected to form self-assembled networks, strengthening the interfacial film as a whole. In this study, whey proteins were conjugated with gellan polysaccharides using the Maillard reaction. Atomic force microscopy images of interfacial films formed by the whey protein-gellan conjugate at the air-water interface and transferred onto mica sheets using the Langmuir-Blodgett method revealed that gellan did form self-assembled networks at the interface and that interfacial films also contained a large number of unconjugated whey protein molecules. Following the addition of a small-molecule surfactant (Tween 20) to the sub-phase, surface pressure increased, indicating spontaneous adsorption of surfactants to the interface. Atomic force microscopy images showed decreases in interfacial area coverage by whey proteins as surface pressure increased. At a given surface pressure, the interfacial area coverage by whey protein-gellan conjugates was greater than coverage by unconjugated whey proteins, confirming that whey proteins became more resistant to surfactant-induced displacement after

  10. Corticosteroids and surfactant change lung function and protein leaks in the lungs of ventilated premature rabbits.

    OpenAIRE

    Ikegami, M; Berry, D.(University of Illinois at Chicago (UIC), Chicago, USA); elKady, T; Pettenazzo, A; Seidner, S; Jobe, A

    1987-01-01

    Fetal rabbits were treated with corticosteroids by maternal administration for 48 h before delivery at 27 d gestational age. The treated and control rabbits were placed on ventilator-plethysmographs so that ventilation could be adjusted by regulation of tidal volumes to 10-13 ml/kg body wt. [125I]albumin was mixed with fetal lung fluid at birth, alternate rabbits from each litter were treated with Surfactant-TA, and [131I]albumin was injected intravascularly. The movement of the labeled album...

  11. Palmitoylation of Pulmonary Surfactant Protein SP-C Is Critical for Its Functional Cooperation with SP-B to Sustain Compression/Expansion Dynamics in Cholesterol-Containing Surfactant Films

    Science.gov (United States)

    Baumgart, Florian; Ospina, Olga L.; Mingarro, Ismael; Rodríguez-Crespo, Ignacio; Pérez-Gil, Jesús

    2010-01-01

    Recent data suggest that a functional cooperation between surfactant proteins SP-B and SP-C may be required to sustain a proper compression-expansion dynamics in the presence of physiological proportions of cholesterol. SP-C is a dually palmitoylated polypeptide of 4.2 kDa, but the role of acylation in SP-C activity is not completely understood. In this work we have compared the behavior of native palmitoylated SP-C and recombinant nonpalmitoylated versions of SP-C produced in bacteria to get a detailed insight into the importance of the palmitic chains to optimize interfacial performance of cholesterol-containing surfactant films. We found that palmitoylation of SP-C is not essential for the protein to promote rapid interfacial adsorption of phospholipids to equilibrium surface tensions (∼22 mN/m), in the presence or absence of cholesterol. However, palmitoylation of SP-C is critical for cholesterol-containing films to reach surface tensions ≤1 mN/m at the highest compression rates assessed in a captive bubble surfactometer, in the presence of SP-B. Interestingly, the ability of SP-C to facilitate reinsertion of phospholipids during expansion was not impaired to the same extent in the absence of palmitoylation, suggesting the existence of palmitoylation-dependent and -independent functions of the protein. We conclude that palmitoylation is key for the functional cooperation of SP-C with SP-B that enables cholesterol-containing surfactant films to reach very low tensions under compression, which could be particularly important in the design of clinical surfactants destined to replacement therapies in pathologies such as acute respiratory distress syndrome. PMID:21081071

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

    DEFF Research Database (Denmark)

    Plasencia, I; Rivas, L; Casals, C;

    2001-01-01

    Predictive studies suggest that the known sequences of the N-terminal segment of surfactant protein SP-C from animal species have an intrinsic tendency to form beta-turns, but there are important differences on the probable location of these motifs in different SP-C species. Our hypothesis is that......-C, and studied their structural behaviour in solution and in phospholipid bilayers and monolayers. In these peptides, leucine at position 1 of both sequences has been replaced by tryptophan in order to allow their study by fluorescence spectroscopy. Far-u.v. circular dichroism spectra of the peptides in...... perturbed the packing of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) monolayers, the effects being always higher in anionic than in zwitterionic lipids, and also substantially higher in films containing canine peptide in comparison to porcine peptide. Acylation of...

  13. 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; Garred, Peter; Jacobsen, Søren

    2014-01-01

    To investigate whether polymorphisms in genes coding for mannose-binding lectin (MBL) and surfactant protein-D (SP-D) are associated directly or by interaction with smoking with rheumatoid arthritis (RA), anti-citrullinated peptide antibody (ACPA) positive RA, and erosive RA. MBL2 genotypes, SFTPD...... genotype at codon 11, and HLA-shared epitope were determined in 456 patients with rheumatoid arthritis and 533 sex- and age-matched controls. Patients were grouped according to the presence of ACPA antibodies and RA-associated bone erosions and sub-stratified according to smoking status as never or ever...... with RA but with erosive RA by interaction with smoking. The genetic disposition for high MBL production was associated with ACPA positive RA irrespective of shared epitope. The findings need to be replicated but do as such offer further explanations for the clinical heterogeneity of RA....

  14. Interactions of the C-terminus of lung surfactant protein B with lipid bilayers are modulated by acyl chain saturation.

    Science.gov (United States)

    Antharam, Vijay C; Farver, R Suzanne; Kuznetsova, Anna; Sippel, Katherine H; Mills, Frank D; Elliott, Douglas W; Sternin, Edward; Long, Joanna R

    2008-11-01

    Lung surfactant protein B (SP-B) is critical to minimizing surface tension in the alveoli. The C-terminus of SP-B, residues 59-80, has much of the surface activity of the full protein and serves as a template for the development of synthetic surfactant replacements. The molecular mechanisms responsible for its ability to restore lung compliance were investigated with circular dichroism, differential scanning calorimetry, and (31)P and (2)H solid-state NMR spectroscopy. SP-B(59-80) forms an amphipathic helix which alters lipid organization and acyl chain dynamics in fluid lamellar phase 4:1 DPPC:POPG and 3:1 POPC:POPG MLVs. At higher levels of SP-B(59-80) in the POPC:POPG lipid system a transition to a nonlamellar phase is observed while DPPC:POPG mixtures remain in a lamellar phase. Deuterium NMR shows an increase in acyl chain order in DPPC:POPG MLVs on addition of SP-B(59-80); in POPC:POPG MLVs, acyl chain order parameters decrease. Our results indicate SP-B(59-80) penetrates deeply into DPPC:POPG bilayers and binds more peripherally to POPC:POPG bilayers. Similar behavior has been observed for KL(4), a peptide mimetic of SP-B which was originally designed using SP-B(59-80) as a template and has been clinically demonstrated to be successful in treating respiratory distress syndrome. The ability of these helical peptides to differentially partition into lipid lamellae based on their degree of monounsaturation and subsequent changes in lipid dynamics suggest a mechanism for lipid organization and trafficking within the dynamic lung environment. PMID:18694722

  15. Sequences of a hairpin structure in the 3′-untranslated region mediate regulation of human pulmonary surfactant protein B mRNA stability

    OpenAIRE

    Huang, Helen W.; Payne, David E.; Bi, Weizhen; Pan, Su; Bruce, Shirley R.; Alcorn, Joseph L.

    2012-01-01

    The ability of pulmonary surfactant to reduce alveolar surface tension requires adequate expression of surfactant protein B (SP-B). Dexamethasone (DEX, 10−7 M) increases human SP-B mRNA stability by a mechanism that requires a 126-nt-long segment (the 7.6S region) of the 3′-untranslated region (3′-UTR). The objective of this study was to identify sequences in the 7.6S region that mediate regulation of SP-B mRNA stability. The 7.6S region was found to be sufficient for DEX-mediated stabilizati...

  16. Cold-inducible RNA binding protein regulates mucin expression induced by cold temperatures in human airway epithelial cells.

    Science.gov (United States)

    Ran, DanHua; Chen, LingXiu; Xie, WenYue; Xu, Qing; Han, Zhong; Huang, HuaPing; Zhou, XiangDong

    2016-08-01

    Mucus overproduction is an important manifestation of chronic airway inflammatory diseases, however, the mechanisms underlying the association between cold air and mucus overproduction remain unknown. We found that the expression of the cold-inducible RNA binding protein (CIRP) was increased in patients with chronic obstructive pulmonary disease (COPD). In the present study, we tested whether CIRP was involved in inflammatory factors and mucin5AC (MUC5AC) expression after cold stimulation and investigated the potential signaling pathways involved in this process. We found that CIRP was highly expressed in the bronchi of COPD patients. The expression of CIRP, interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) were increased, and the CIRP was localized in cytoplasm after cold stimulation. MUC5AC mRNA and protein expression levels were elevated in a temperature- and time-dependent manner after cold stimulation and were associated with the phosphorylation of ERK and NF-κB, which reflected their activation. These responses were suppressed by knockdown of CIRP with a specific siRNA or the ERK and NF-κB inhibitors. These results demonstrated that CIRP was expressed in the bronchi of human COPD patients and was involved in inflammatory factors and MUC5AC expression after cold stimulation through the ERK and NF-κB pathways. PMID:27184164

  17. Preparation of protein based surfactants from leather waste fleshings and their reutilization in leather as a water resisting agent

    International Nuclear Information System (INIS)

    Summary: Tanneries generate a huge amount of highly polluting solid and liquid wastes during leather processing at different stages such as fleshings, shavings, tanning, finishing etc. approximately, 250 kg of finished leather product is obtained from 1 ton of raw salted hide while other protein goes into wastes. leather fleshings are about 50-60% of the total solid waste generated in leather processing. three different surfactants have been prepared from soft wax, long chain fatty acid chlorides and leather waste protein isolated from alkaline hydrolysis of fleshings. products are milky in color and have been applied in goat leathers as a replacement of fat liquor and water resisting agent .the resulted crust leathers have been characterized for various physical parameters such as tensile strength, thickness, softness, tear strength, bursting load, water absorption etc, as per their standard test methods. leathers have also been evaluated for grain smoothness, fullness and feeling. leathers have shown satisfactory results as per international requirement specially for water resisting. thus a leather waste protein is converted into a useful product and reutilized in leather making. (author)

  18. NCPAP联合PS治疗早产儿肺透明膜病的临床效果研究%Effect of nasal continuous positive airway pressure and pulmonary surfactant on hyaline membrane disease in premuture infant

    Institute of Scientific and Technical Information of China (English)

    郑莉

    2013-01-01

    Objective To discuss the clinical effects of nasal continuous positive airway pressure and pulmonary surfactant on hyaline membrane disease in premuture infant. Methods 108 premature infant with hyaline membrane disease were selected from Janauary 2010 to March 2013 in our hospital. And they were randomly divided into three group,A group were received NCPAP and PS , B group were just received NCPAP,C group were only recived PS.Breath,heart rate,blood pressure and blood gas were analyzed. Results Premature infants in all groups showed significantly therapeutically effect on breath,heart rate,blood pressure and blood gas analysis after therapy(P<0.05). While premature infants in A group showed significantly therapeutically effect on breath, heart rate,PaO2, PaCO2 and SaO2 than other groups(P < 0.05). Conclusion NCPAP and PS presented significant therapeutically effect,and improved life quality and reduce adverse effect,which should be worth to extend in clinical.%  目的探讨NCPAP联合PS治疗早产儿肺透明膜病的临床效果。方法收集我院2010年1月~2013年3月治疗的肺透明膜病早产儿108例,随机分为三组,A组给予鼻塞持续气道正压通气(NCPAP)、肺表明活性物质(PS)治疗,B组给予NCPAP治疗,C组给予肺表面活性物质(PS)治疗。观察各组患儿治疗前后呼吸、心率、血压及血气分析等。结果各组患儿治疗后的呼吸、心率、PaO2均与治疗前比较,差异有统计学意义(P<0.05)。其中A组患儿治疗后呼吸、心率及PaO2、PaCO2、SaO2与C组治疗后比较,差异有统计学意义(P<0.05)。结论NCPAP联合PS具有较好的临床治疗效果,提高患儿生存质量,减少不良反应的发生,值得临床广泛推广。

  19. Differential susceptibility of transgenic mice expressing human surfactant protein B genetic variants to Pseudomonas aeruginosa induced pneumonia.

    Science.gov (United States)

    Ge, Lin; Liu, Xinyu; Chen, Rimei; Xu, Yongan; Zuo, Yi Y; Cooney, Robert N; Wang, Guirong

    2016-01-01

    Surfactant protein B (SP-B) is essential for lung function. Previous studies have indicated that a SP-B 1580C/T polymorphism (SNP rs1130866) was associated with lung diseases including pneumonia. The SNP causes an altered N-linked glycosylation modification at Asn129 of proSP-B, e.g. the C allele with this glycosylation site but not in the T allele. This study aimed to generate humanized SP-B transgenic mice carrying either SP-B C or T allele without a mouse SP-B background and then examine functional susceptibility to bacterial pneumonia in vivo. A total of 18 transgenic mouse founders were generated by the DNA microinjection method. These founders were back-crossed with SP-B KO mice to eliminate mouse SP-B background. Four founder lines expressing similar SP-B levels to human lung were chosen for further investigation. After intratracheal infection with 50 μl of Pseudomonas aeruginosa solution (1 × 10(6) CFU/mouse) or saline in SP-B-C, SP-B-T mice the mice were sacrificed 24 h post-infection and tissues were harvested. Analysis of surfactant activity revealed differential susceptibility between SP-B-C and SP-B-T mice to bacterial infection, e.g. higher minimum surface tension in infected SP-B-C versus infected SP-B-T mice. These results demonstrate for the first time that human SP-B C allele is more susceptible to bacterial pneumonia than SP-B T allele in vivo. PMID:26620227

  20. Immunohistochemical characteristics of surfactant proteins a, B, C and d in inflammatory and tumorigenic lung lesions of f344 rats.

    Science.gov (United States)

    Yokohira, Masanao; Yamakawa, Keiko; Nakano, Yuko; Numano, Takamasa; Furukawa, Fumio; Kishi, Sosuke; Ninomiya, Fumiko; Kanie, Shohei; Hitotsumachi, Hiroko; Saoo, Kousuke; Imaida, Katsumi

    2014-10-01

    Surfactant proteins (SPs), originally known as human lung surfactants, are essential to respiratory structure and function. There are 4 subtypes, SP-A, SP-B, SP-C and SP-D, with SP-A and SP-D having immunological functions, and SP-B and SP-C having physicochemical properties that reduce the surface tension at biological interfaces. In this experiment, the expressions of SP-A, SP-B, SP-C and SP-D in lung neoplastic lesions induced by N-bis (2-hydroxypropyl) nitrosamine (DHPN) and inflammatory lesions due to quartz instillation were examined and compared immunohistochemically. Formalin fixed paraffin embedded (FFPE) lung samples featuring inflammation were obtained with a rat quartz instillation model, and neoplastic lesions, hyperplasias and adenomas, were obtained with the rat DHPN-induced lung carcinogenesis model. In the rat quartz instillation model, male 10-week old F344 rats were exposed by intratracheal instillation (IT) to quartz at a dose of 2 mg/rat suspended in saline (0.2 ml) on day 0, and sacrificed on day 28. Lung tumorigenesis in F344 male rats was initiated by DHPN in drinking water for 2 weeks, and the animals were then sacrificed in week 30. Lung proliferative lesions, hyperplasias and adenomas, were observed with DHPN, and inflammation was observed with quartz. The expressions of SP-A, SP-B, SP-C and SP-D were examined immunohistochemically. SP-B and SP-C showed strong expression in lung hyperplasias and adenomas, while SP-A and SP-D were observed in mucus or exudates in inflammatory alveoli. These results suggest the possibility that SP-B and SP-C are related to lung tumorigenesis. PMID:25378802

  1. The impact of surfactant protein-A on ozone-induced changes in the mouse bronchoalveolar lavage proteome

    Directory of Open Access Journals (Sweden)

    Floros Joanna

    2009-03-01

    Full Text Available Abstract Background Ozone is a major component of air pollution. Exposure to this powerful oxidizing agent can cause or exacerbate many lung conditions, especially those involving innate immunity. Surfactant protein-A (SP-A plays many roles in innate immunity by participating directly in host defense as it exerts opsonin function, or indirectly via its ability to regulate alveolar macrophages and other innate immune cells. The mechanism(s responsible for ozone-induced pathophysiology, while likely related to oxidative stress, are not well understood. Methods We employed 2-dimensional difference gel electrophoresis (2D-DIGE, a discovery proteomics approach, coupled with MALDI-ToF/ToF to compare the bronchoalveolar lavage (BAL proteomes in wild type (WT and SP-A knockout (KO mice and to assess the impact of ozone or filtered air on the expression of BAL proteins. Using the PANTHER database and the published literature most identified proteins were placed into three functional groups. Results We identified 66 proteins and focused our analysis on these proteins. Many of them fell into three categories: defense and immunity; redox regulation; and protein metabolism, modification and chaperones. In response to the oxidative stress of acute ozone exposure (2 ppm; 3 hours there were many significant changes in levels of expression of proteins in these groups. Most of the proteins in the redox group were decreased, the proteins involved in protein metabolism increased, and roughly equal numbers of increases and decreases were seen in the defense and immunity group. Responses between WT and KO mice were similar in many respects. However, the percent change was consistently greater in the KO mice and there were more changes that achieved statistical significance in the KO mice, with levels of expression in filtered air-exposed KO mice being closer to ozone-exposed WT mice than to filtered air-exposed WT mice. Conclusion We postulate that SP-A plays a role

  2. 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

    2015-06-01

    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.

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

    Science.gov (United States)

    van 't Wout, Emily F A; van Schadewijk, Annemarie; van Boxtel, Ria; Dalton, Lucy E; Clarke, Hanna J; Tommassen, Jan; Marciniak, Stefan J; Hiemstra, Pieter S

    2015-06-01

    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. PMID:26083346

  4. 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: ondalgl@cdc.go.kr [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of)

    2011-04-22

    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

  5. Diseases of Pulmonary Surfactant Homeostasis

    OpenAIRE

    Jeffrey A Whitsett; Wert, Susan E.; Weaver, Timothy E.

    2015-01-01

    Advances in physiology and biochemistry have provided fundamental insights into the role of pulmonary surfactant in the pathogenesis and treatment of preterm infants with respiratory distress syndrome. Identification of the surfactant proteins, lipid transporters, and transcriptional networks regulating their expression has provided the tools and insights needed to discern the molecular and cellular processes regulating the production and function of pulmonary surfactant prior to and after bi...

  6. Antiviral activity of recombinant porcine surfactant protein A against porcine reproductive and respiratory syndrome virus in vitro.

    Science.gov (United States)

    Li, Lan; Zheng, Qisheng; Zhang, Yuanpeng; Li, Pengcheng; Fu, Yanfeng; Hou, Jibo; Xiao, Xilong

    2016-07-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) has caused significant economic losses in the swine industry worldwide. However, there is not an ideal vaccine to provide complete protection against PRRSV. Thus, the need for new antiviral strategies to control PRRSV still remains. Surfactant protein A (SP-A) belongs to the family of C-type lectins, which can exert antiviral activities. In this present study, we assessed the antiviral properties of recombinant porcine SP-A (RpSP-A) on PRRSV infection in Marc 145 cells and revealed its antiviral mechanism using a plaque assay, real-time qPCR, western blotting analysis and an attachment and penetration assay. Our results showed that RpSP-A could inhibit the infectivity of PRRSV in Marc 145 cells and could reduce the total RNA and protein level. The attachment assay indicated that RpSP-A in the presence of Ca(2+) could largely inhibit Marc 145 cell attachment; however, in the penetration assay, it was relatively inactive. Furthermore, our study suggested that virus progeny released from infected Marc145 cells were blocked by RpSP-A from infecting other cells. We conclude that RpSP-A has antiviral activity against PRRSV, most probably by blocking viral attachment and the cell-to-cell transmission pathway, and therefore, RpSP-A holds promise as a novel antiviral agent against PRRSV. PMID:27101074

  7. Surface properties and sensitivity to protein-inhibition of a recombinant apoprotein C-based phospholipid mixture in vitro--comparison to natural surfactant.

    Science.gov (United States)

    Seeger, W; Thede, C; Günther, A; Grube, C

    1991-01-01

    Surfactant alterations due to protein leakage are implicated in the pathogenesis of the adult respiratory distress syndrome. In the present study, surface properties of a palmitic acid containing phospholipid mixture (DPPC: PG: PA/68.5:22.5:9) supplemented with 2% recombinant human surfactant apoprotein C (PLM-Crec) were compared to those of the lipids alone (PLM) and to those of calf lung surfactant extract (CLSE). Experiments were performed in a Wilhelmy balance and in a pulsating bubble surfactometer. Adsorption facilities and dynamic surface tension-lowering properties of the surfactants alone, their sensitivity to the inhibitory effect of fibrinogen (fbg), and their capacity to restore surface properties of fbg-inhibited CLSE were investigated. PLM revealed limited surface activity, was very sensitive to inhibition by fbg and had moderate effect on the surface properties of fbg-inhibited CLSE. In contrast, PLM-Crec and CLSE revealed similar excellent adsorption kinetics and dynamic surface tension lowering properties. Higher percentage of SP-C within the synthetic mixture (up to 10%) or additional admixture of human purified or recombinant SP-A (up to 10%) did not further improve these surface properties. However, PLM-Crec was markedly more sensitive to inactivation by fbg than CLSE. The surface activity of fbg-inhibited CLSE was fully restored by additional admixture of CLSE or PLM-Crec in both the Wilhelmy and the bubble system, with slight superiority of the natural surfactant extract. We conclude that the surface properties of PLM-Crec are clearly superior to those of the apoprotein-free lipid mixture and are similar to those of the natural surfactant extract CLSE. PLM-Crec is markedly more sensitive to inhibition by fibrinogen than CLSE, but possesses nearly equivalent efficacy in restoring the surface properties of fbg-inhibited CLSE as compared to the natural material. PMID:1991155

  8. Sex differences in the response of the alveolar macrophage proteome to treatment with exogenous surfactant protein-A

    Directory of Open Access Journals (Sweden)

    Phelps David S

    2012-07-01

    Full Text Available Abstract Background Male wild type (WT C57BL/6 mice are less capable of clearing bacteria and surviving from bacterial pneumonia than females. However, if an oxidative stress (acute ozone exposure occurs before infection, the advantage shifts to males who then survive at higher rates than females. We have previously demonstrated that survival in surfactant protein-A (SP-A knockout (KO mice compared to WT was significantly reduced. Because the alveolar macrophage (AM is pivotal in host defense we hypothesized that SP-A and circulating sex hormones are responsible for these sex differences. We used 2D-DIGE to examine the relationship of sex and SP-A on the AM proteome. The role of SP-A was investigated by treating SP-A KO mice with exogenous SP-A for 6 and 18 hr and studying its effects on the AM proteome. Results We found: 1 less variance between KO males and females than between the WT counterparts by principal component analysis, indicating that SP-A plays a role in sex differences; 2 fewer changes in females when the total numbers of significantly changing protein spots or identified whole proteins in WT or 18 hr SP-A-treated males or females were compared to their respective KO groups; 3 more proteins with functions related to chaperones or protease balance and Nrf2-regulated proteins changed in response to SP-A in females than in males; and 4 the overall pattern of SP-A induced changes in actin-related proteins were similar in both sexes, although males had more significant changes. Conclusions Although there seems to be an interaction between sex and the effect of SP-A, it is unclear what the responsible mechanisms are. However, we found that several of the proteins that were expressed at significantly higher levels in females than in males in WT and/or in KO mice are known to interact with the estrogen receptor and may thus play a role in the SP-A/sex interaction. These include major vault protein, chaperonin subunit 2 (beta (CCT2, and Rho

  9. Surfactant gene polymorphisms and interstitial lung diseases

    Directory of Open Access Journals (Sweden)

    Pantelidis Panagiotis

    2001-11-01

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

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

    Science.gov (United States)

    Jeong, Young-Il; Kim, Seung Hyun; Ju, Jung Won; Cho, Shin Hyeong; Lee, Won Ja; Park, Jin Wook; Park, Yeong-Min; Lee, Sang Eun

    2011-04-22

    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(+)CD25(+)Foxp3(+) 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 naïve T cells. These data demonstrate the capacity of C. sinensis to ameliorate allergic asthma and broaden our understanding of the paradoxical relationship between the allergic immune response and helminth infection. PMID:21440530

  11. Acute chlorine gas exposure produces transient inflammation and a progressive alteration in surfactant composition with accompanying mechanical dysfunction

    International Nuclear Information System (INIS)

    Acute Cl2 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 Cl2 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 Cl2 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. Cl2 exposure had no effect on NOS2 mRNA or iNOS protein expression, nor on BAL NO3− or NO2−. 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. Cl2 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 Cl2 inhalation. - Highlights: • Effect of 60 ppm*hr Cl2 gas on lung inflammation and mechanical function examined. • Pulmonary inflammation is transient and minor. • Alterations in surfactant homeostasis and pulmonary mechanics

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    seen to recombinant SP-A composed of the neck region and carbohydrate recognition domain of SP-A indicating that the interaction between MFAP4 and SP-A is mediated via the collagen domain of SP-A. Monoclonal antibodies directed against MFAP4 and SP-A were used for immunohistochemical analysis, which......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...... 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...

  13. Three-dimensional model of surfactant replacement therapy

    OpenAIRE

    Filoche, Marcel; Tai, Cheng-Feng; Grotberg, James B.

    2015-01-01

    To our knowledge, this paper presents the first structural model of surfactant replacement therapy (SRT), the delivery of liquid bolus surfactant mixtures into the lung airways. SRT has succeeded in premature neonates with surfactant deficiency but mostly failed in adults with acute respiratory distress syndrome, which claims ∼74,500 lives annually in the United States at a 39% mortality rate. Our model incorporates the fluid mechanics of the liquid bolus propagating through a branching airwa...

  14. Surfactant administration in neonates: A review of delivery methods

    OpenAIRE

    Nouraeyan, Nina; Lambrinakos-Raymond, Alicia; Leone, Marisa; Sant’Anna, Guilherme

    2014-01-01

    Surfactant has revolutionized the treatment of respiratory distress syndrome and some other respiratory conditions that affect the fragile neonatal lung. Despite its widespread use, the optimal method of surfactant administration in preterm infants has yet to be clearly determined. The present article reviews several aspects of administration techniques that can influence surfactant delivery into the pulmonary airways: the bolus volume, injection rate, gravity and orientation, ventilation str...

  15. Comparative nasal effects of bradykinin and histamine: influence on nasal airways resistance and plasma protein exudation.

    OpenAIRE

    Rajakulasingam, K.; Polosa, R; Lau, L.C.; Church, M. K.; Holgate, S T; Howarth, P. H.

    1993-01-01

    BACKGROUND--Bradykinin may contribute to the pathogenesis of allergic rhinitis. Like histamine, nasal challenge with bradykinin induces rhinorrhoea, nasal blockage, and plasma protein leakage. Their comparative nasal potencies have not, however, been fully elucidated. METHODS--Three double blind, randomised, placebo controlled and cross-over studies were undertaken to compare objectively the nasal effects of bradykinin, histamine, and vehicle. RESULTS--Both bradykinin and histamine produced d...

  16. Level of Fatty Acid Binding Protein 5 (FABP5 Is Increased in Sputum of Allergic Asthmatics and Links to Airway Remodeling and Inflammation.

    Directory of Open Access Journals (Sweden)

    Hille Suojalehto

    Full Text Available The inflammatory processes in the upper and lower airways in allergic rhinitis and asthma are similar. Induced sputum and nasal lavage fluid provide a non-invasive way to examine proteins involved in airway inflammation in these conditions.We conducted proteomic analyses of sputum and nasal lavage fluid samples to reveal differences in protein abundances and compositions between the asthma and rhinitis patients and to investigate potential underlying mechanisms.Induced sputum and nasal lavage fluid samples were collected from 172 subjects with 1 allergic rhinitis, 2 asthma combined with allergic rhinitis, 3 nonallergic rhinitis and 4 healthy controls. Proteome changes in 21 sputum samples were analysed with two-dimensional difference gel electrophoresis (2D-DIGE, and the found differentially regulated proteins identified with mass spectrometry. Immunological validation of identified proteins in the sputum and nasal lavage fluid samples was performed with Western blot and ELISA.Altogether 31 different proteins were identified in the sputum proteome analysis, most of these were found also in the nasal lavage fluid. Fatty acid binding protein 5 (FABP5 was up-regulated in the sputum of asthmatics. Immunological validation in the whole study population confirmed the higher abundance levels of FABP5 in asthmatic subjects in both the sputum and nasal lavage fluid samples. In addition, the vascular endothelial growth factor (VEGF level was increased in the nasal lavage fluid of asthmatics and there were positive correlations between FABP5 and VEGF levels (r=0.660, p<0.001 and concentrations of FABP5 and cysteinyl leukotriene (CysLT (r=0.535, p<0.001 in the nasal lavage fluid.FABP5 may contribute to the airway remodeling and inflammation in asthma by fine-tuning the levels of CysLTs, which induce VEGF production.

  17. Cry1Ab protein from Bacillus thuringiensis and MON810 cry1Ab-transgenic maize exerts no adjuvant effect after airway exposure.

    Science.gov (United States)

    Andreassen, M; Bøhn, T; Wikmark, O-G; Van den Berg, J; Løvik, M; Traavik, T; Nygaard, U C

    2015-03-01

    The genetically modified (GM) maize event MON810 has been inserted with a processed version of the transgene, cry1Ab, derived from the soil bacterium Bacillus thuringiensis (Bt) to express proteins with insecticidal properties. Such proteins may introduce new allergens and also act as adjuvants that promote allergic responses. While focus has been on safe consumption and hence the oral exposure to GM food and feed, little is known regarding inhalation of pollen and desiccated airborne plant material from GM crops. The aim of this study was to investigate whether plant material from the Cry1Ab-expressing maize variety MON810, or trypsin-activated Cry1Ab (trypCry1Ab) protein produced in recombinant bacteria, may act as adjuvants against the allergen ovalbumin (OVA) in a mouse model of airway allergy. A clear proallergic adjuvant effect of the mucosal adjuvant cholera toxin (CT) was demonstrated, determined as increased specific IgE, eosinophils and Th2 cytokines in MLN cell supernates, while no elevation in OVA-specific antibodies or cytokine release from MLN cells after stimulation with OVA were observed in mice receiving Cry1Ab-containing plant materials or the trypCry1Ab protein. Our data suggest that Cry1Ab proteins had no detectable systemic adjuvant effect in mice after airway exposure. Further experiments with purified plant proteins, as well as long-term exposures needs be conducted to further evaluate exposures experienced in real-life situations. PMID:25564738

  18. Selective adsorption of proteins on single-wall carbon nanotubes by using a protective surfactant.

    Science.gov (United States)

    Knyazev, Anton; Louise, Loïc; Veber, Michèle; Langevin, Dominique; Filoramo, Arianna; Prina-Mello, Adriele; Campidelli, Stéphane

    2011-12-16

    The dispersion of highly hydrophobic carbon materials such as carbon nanotubes in biological media is a challenging issue. Indeed, the nonspecific adsorption of proteins occurs readily when the nanotubes are introduced in biological media; therefore, a methodology to control adsorption is in high demand. To address this issue, we developed a bifunctional linker derived from pyrene that selectively enables or prevents the adsorption of proteins on single-wall carbon nanotubes (SWNTs). We demonstrated that it is possible to decrease or completely suppress the adsorption of proteins on the nanotube sidewall by using proper functionalization (either covalent or noncovalent). By subsequently activating the functional groups on the nanotube derivatives, protein adsorption can be recovered and, therefore, controlled. Our approach is simple, straightforward, and potentially suitable for other biomolecules that contain thio or amino groups available for coupling. PMID:22095560

  19. Clouding behaviour in surfactant systems.

    Science.gov (United States)

    Mukherjee, Partha; Padhan, Susanta K; Dash, Sukalyan; Patel, Sabita; Mishra, Bijay K

    2011-02-17

    A study on the phenomenon of clouding and the applications of cloud point technology has been thoroughly discussed. The phase behaviour of clouding and various methods adopted for the determination of cloud point of various surfactant systems have been elucidated. The systems containing anionic, cationic, nonionic surfactants as well as microemulsions have been reviewed with respect to their clouding phenomena and the effects of structural variation in the surfactant systems have been incorporated. Additives of various natures control the clouding of surfactants. Electrolytes, nonelectrolytes, organic substances as well as ionic surfactants, when present in the surfactant solutions, play a major role in the clouding phenomena. The review includes the morphological study of clouds and their applications in the extraction of trace inorganic, organic materials as well as pesticides and protein substrates from different sources. PMID:21296314

  20. Interdependent TTF1 - ErbB4 interactions are critical for surfactant protein-B homeostasis in primary mouse lung alveolar type II cells

    OpenAIRE

    Marten, Elger; Nielsen, Heber C.; Dammann, Christiane E. L.

    2015-01-01

    ErbB4 receptor and thyroid transcription factor (TTF)-1 are important modulators of fetal alveolar type II (ATII) cell development and injury. ErbB4 is an upstream regulator of TTF-1, promoting its expression in MLE-12 cells, an ATII cell line. Both proteins are known to promote surfactant protein-B gene (SftpB) and protein (SP-B) expression, but their feedback interactions on each other are not known. We hypothesized that TTF-1 expression has a feedback effect on ErbB4 expression in an in-vi...

  1. Genetic disorders of surfactant homeostasis.

    Science.gov (United States)

    Whitsett, Jeffrey A; Wert, Susan E; Xu, Yan

    2005-01-01

    Adaptation to air breathing at birth requires the precise orchestration of cellular processes to initiate fluid clearance, enhance pulmonary blood flow, and to synthesize and secrete pulmonary surfactant needed to reduce surface tension at the air-liquid interface in the alveoli. Genetic programs regulating the synthesis of the surfactant proteins and lipids required for the production and function of pulmonary surfactant are highly conserved across vertebrates, and include proteins that regulate the synthesis and packaging of pulmonary surfactant proteins and lipids. Surfactant proteins B and C (SP-B and -C) are small, uniquely hydrophobic proteins that play important roles in the stability and spreading of surfactant lipids in the alveolus. Deletion or mutations in SP-B and -C cause acute and chronic lung disease in neonates and infants. SP-B and -C are synthesized and packaged with surfactant phospholipids in lamellar bodies. Normal lamellar body formation requires SP-B and a member of the ATP-binding cassette (ABC) family of ATP-dependent membrane-associated transport proteins, ABCA3. Mutations in ABCA3 cause fatal respiratory disease in newborns and severe chronic lung disease in infancy. Expression of SP-B, -C, and ABCA3 are coregulated during late gestation by transcriptional programs influenced by thyroid transcription factor-1 and forkhead box a2, transcription factors that regulate both differentiation of the respiratory epithelium and transcription of genes required for perinatal adaptation to air breathing. PMID:15985750

  2. Elevation of Serum KL-6 Glycoprotein or Surfactant Protein-D in Adult T-cell Leukemia with Distinct Pulmonary Complications

    OpenAIRE

    Osaka, Akemi; Yanagihara, Katsunori; Yamada, Yasuaki; Hasegawa, Hiroo; Inokuchi, Naoko; Hayashi, Tomayoshi; Komoda, Minori; Nakamura, Shigeki; Aoyama, Muneo; Sawada, Takashi; Kamihira, Shimeru

    2009-01-01

    Patients with hematological malignancies frequently suffer from lung diseases as a complication. However, it is difficult to discriminate leukemic invasion into the lung from infectious pulmonary complications. The serum level of Krebs von den Lungen-6 (KL-6), which is a mucin-like glycoprotein, is increased in more than 70% of patients with interstitial pneumonia. Surfactant protein-D (SP-D) is produced mainly in the lung by alveolar type II and bronchiolar epithelial cells and is a useful s...

  3. Epithelial expression of mRNA and protein for IL-6, IL-10 and TNF-α in endobronchial biopsies in horses with recurrent airway obstruction

    Directory of Open Access Journals (Sweden)

    Art Tatiana

    2008-02-01

    Full Text Available Abstract Background The aim of this study was to evaluate the contribution of bronchial epithelium to airway inflammation, with focus on mRNA and protein expression of cytokines of innate immunity IL-6, IL-10 and TNF-α, in horses with Recurrent Airway Obstruction (RAO during exacerbation and in remission. Results Despite marked clinical and physiologic alterations between exacerbation and after remission in the RAO horses no differences were detected in either cytokine mRNA or protein levels. Moreover, the expression of investigated cytokines in RAO horses on pasture did not differ from controls. In comparing real-time PCR analysis to results of immunohistochemistry only IL-10 mRNA and protein levels in RAO horses on pasture were significantly correlated (rs = 0.893, p = 0.007. Curiously, in controls examined on pasture the TNF-α protein level was positively correlated to IL-10 mRNA expression (rs = 0.967, p = 0.007 and negatively correlated to IL-6 mRNA expression (rs = -0.971, p = 0.001. Conclusion Given the complementary relationship of assessing cytokines directly by immunohistochemistry, or indirectly by PCR to mRNA, the lack of significant changes in either mRNA or protein levels of IL-6, IL-10 or TNF-α mRNA in RAO horses in exacerbation suggests that these particular cytokines in bronchial tissue may not play a substantive role in the active inflammation of this disease. To support this contention further studies examining time dependency of expression of IL-6, IL-10 or TNF-α are needed, as is expansion of the range of cytokines to include other key regulators of airway inflammation.

  4. Surfactant Protein B Deficiency Caused by Homozygous C248X Mutation—A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Stefan Kurath-Koller

    2015-04-01

    Full Text Available Objective - Surfactant protein B (SP-B deficiency is a rare autosomal recessive disorder that is usually rapidly fatal. The c.397delCinsGAA mutation (121ins2 in exon 4 is found in more than two-thirds of patients. Design - We report on a fatal case of SP-B deficiency caused by a homozygous C248X mutation in exon 7 of the SP-B gene. In addition, we provide an update of the current literature. The EMBASE, MEDLINE, and CINAHL databases were systematically searched to identify all papers published in the English and German literature on SP-B deficiency between 1989 and 2013. Results - SP-B deficiency is characterized by progressive hypoxemic respiratory failure generally in full-term infants. They present with symptoms of respiratory distress and hypoxemia; chest X-ray resembles hyaline membrane disease. Prenatal diagnosis is possible from amniotic fluid or chorionic villi sampling. Conclusion - Thirty-four mutations have been published in the literature. Treatment options are scarce. Gene therapy is hoped to be an option in the future.

  5. Effects of the Biomolecules: Vitamins, Proteins, Amino Acids, and Surfactants: DTAB, MTOAC, TMSOI, Orcinol on Upper Critical Solution Temperatures

    Directory of Open Access Journals (Sweden)

    Vinod Kumar

    2007-09-01

    Full Text Available Upper critical solution temperatures (UCSTS ± 0.05 K and mutual solubilities of phenol + water systems are reported separately with 0.5 millimol kg-1 (mm kg-1 proteins (casein, pepsin, egg-albumin, vitamins (B1-thiamine, B2-riboflavin, B6-pyridoxine, amino acids (glycine, β-alanine, L-leucine and surfactants (dodecyl trimethylammonium bromide- DTAB, trimethylsulphoxonium iodide-TMSOI, methyltrioctylammonium chloride- MTOAC, orcinol. The additives decrease the UCSTs by about 0.50-2 0C with slight enhancement in mutual solubilities but the leucine with two –CH3 (methyl and two - CH2- (methylene groups produce negligible increase in the solubilities. The –CH3 and - CH2- groups develop stronger hydrophobic interactions but the glycine develops stronger hydrophilic interactions due to –N+H3 (amino and –COO- (carboxylic groups and weaker hydrophobic due to single –CH2- group. The leucine increases the solubility by 0.009 mole fractions with a 0.7 0C decrease in USCT as compared to phenol-water. The mole fractions of additives restricted to 0.002 to 0.005 range, the conjugations of casein and vitamins in place of –CH3 groups of amino acids enhance the solubility with lower UCST values.

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

    Directory of Open Access Journals (Sweden)

    Planellas Marta

    2012-08-01

    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.

  7. Antigenicity of low molecular weight surfactant species.

    OpenAIRE

    Strayer, D. S.; Merritt, T A; Makunike, C.; Hallman, M

    1989-01-01

    The authors tested the antigenicity of human lung surfactant isolated from amniotic fluid. Mice and rabbits were immunized. Rabbit polyclonal antisera to these surfactant preparations were absorbed with normal human plasma proteins. Polyclonal antisera reacted with both high molecular weight (35 kd) surfactant apoprotein and to lower molecular weight species, both 18 kd and 9 kd. Mice were used to generate monoclonal antibodies to surfactant. Enzyme-linked immunosorbant assay was used to iden...

  8. 肺泡表面活性物质联合气道正压通气治疗新生儿呼吸窘迫综合症的相关护理%The nursing care effects of pulmonary surfactant combined with continuous positive airway pressure in the treatment of NRDS

    Institute of Scientific and Technical Information of China (English)

    袁春梅

    2014-01-01

    目的:探讨肺泡表面活性物质联合气道正压通气治疗新生儿呼吸窘迫综合症的相关护理。方法选择我院100例患有新生儿呼吸窘迫综合症(NRDS)的早产儿,予患儿肺表面活性物理联合气道正压通气(NCPAP)进行治疗。在患儿治疗期间,注意药物的用法用量,病情监测,患儿的保暖,呼吸道管理等综合护理措施。结果经过治疗后36例患儿症状与体征有明显改善。患儿治疗后6h PaO2明显上升(P<0.05),PaCO2明显下降(P<0.05)。结论肺泡表面活性物质联合气道正压通气治疗新生儿呼吸窘迫综合症临床疗效显著,有效降低并发症的发病率,改善了患儿预后情况。%Objective: To explore the nursing care effect of pulmonary surfactant combined with continuous positive airway pressure in the treatment of NRDS. Methods: 100 premature infants enroled in this study were treated with pulmonary surfactant and continuous positive airway pressure. And during the treatment,be aware of the medicine use,monitoring the infants ‘condition and etc. Results: The infants’ condition were greatly improved after the combined treatment. The 6h PaO2 were increased with PaCO2 decreasing. Conclusion:Pulmonary surfactant combined with continuous positive airway pressure have a significant effect in the treatment of NRDS.

  9. Surfactant deficiency in rats without a decreased amount of extracellular surfactant.

    OpenAIRE

    Massaro, D; Clerch, L; Temple, D.; Baier, H.

    1983-01-01

    Low volume ventilation without periodic large inflations leads to diminished alveolar stability and to the accumulation of increased amounts of airway disaturated phosphatidylcholine (DSPC) in large aggregates that sediment at 1,000 g; surfactant in this form lowers surface tension less rapidly than surfactant present in the 1,000-g supernatant fraction. These observations led to the present work in which we tested the notion that alveolar instability may develop in the presence of an undimin...

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

    Directory of Open Access Journals (Sweden)

    Georgios Sotiriadis

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

  11. Long-acting β2-agonists increase fluticasone propionate-induced mitogen-activated protein kinase phosphatase 1 (MKP-1 in airway smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Melanie Manetsch

    Full Text Available Mitogen-activated protein kinase phosphatase 1 (MKP-1 represses MAPK-driven signalling and plays an important anti-inflammatory role in asthma and airway remodelling. Although MKP-1 is corticosteroid-responsive and increased by cAMP-mediated signalling, the upregulation of this critical anti-inflammatory protein by long-acting β2-agonists and clinically-used corticosteroids has been incompletely examined to date. To address this, we investigated MKP-1 gene expression and protein upregulation induced by two long-acting β2-agonists (salmeterol and formoterol, alone or in combination with the corticosteroid fluticasone propionate (abbreviated as fluticasone in primary human airway smooth muscle (ASM cells in vitro. β2-agonists increased MKP-1 protein in a rapid but transient manner, while fluticasone induced sustained upregulation. Together, long-acting β2-agonists increased fluticasone-induced MKP-1 and modulated ASM synthetic function (measured by interleukin 6 (IL-6 and interleukin 8 (IL-8 secretion. As IL-6 expression (like MKP-1 is cAMP/adenylate cyclase-mediated, the long-acting β2-agonist formoterol increased IL-6 mRNA expression and secretion. Nevertheless, when added in combination with fluticasone, β2-agonists significantly repressed IL-6 secretion induced by tumour necrosis factor α (TNFα. Conversely, as IL-8 is not cAMP-responsive, β2-agonists significantly inhibited TNFα-induced IL-8 in combination with fluticasone, where fluticasone alone was without repressive effect. In summary, long-acting β2-agonists increase fluticasone-induced MKP-1 in ASM cells and repress synthetic function of this immunomodulatory airway cell type.

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

    Directory of Open Access Journals (Sweden)

    Kajiki Akira

    2011-03-01

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

  13. Surfactant metabolism in the newborn : The impact of ventilation strategy and lung disease

    OpenAIRE

    Bohlin, Kajsa

    2005-01-01

    Developmental deficiency in pulmonary surfactant leads to respiratory distress syndrome (RDS) in preterm infants, but all newborns may have impaired surfactant metabolism secondary to lung disease or ventilator induced lung injury. Exogenous surfactant treatment is usually administered in conjunction with mechanical ventilation. If instead surfactant administration is followed by nasal continuous positive airway pressure (nCPAP), the treatment response appears to be more sus...

  14. 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; Hansen, Søren; Stenvang, Jan; Thorsen, Stine Buch; Meldgaard, Michael; Kristensen, Bjarne Winther; Hansen, Pernille B. Lærkegaard; Sørensen, Grith Lykke; Finsen, Bente

    2014-01-01

    -induced increase in TNF mRNA production one day after induction of ischemia; however the TNF response to the ischemic insult was affected at five days. SP-D mRNA was not detected in parenchymal brain cells in either naïve mice or in mice subjected to focal cerebral ischemia. However, SP-D mRNA was detected in...... middle cerebral artery cells in WT mice and SP-D protein in vascular cells both in normal appearing and ischemic human brain tissue. Measurements of the levels of SP-D and TNF in plasma in mice suggested that levels were unaffected by the ischemic insult. Microglial-leukocyte and astroglial responses...

  15. Combined Application of 17-Estradiol and Progesterone Enhance Vascular Endothelial Growth Factor and Surfactant Protein Expression in Cultured Embryonic Lung Cells of Mice

    Directory of Open Access Journals (Sweden)

    Andreas Trotter

    2009-01-01

    Full Text Available Preterm delivery is associated with disruption of the placental supply with 17-estradiol (E2 and progesterone (P. The aim is to evaluate the role of E2 and P on the regulation of key proteins in lung development in embryonic lung cells. Alveolar cell type II (AT-II and central lung fibroblast cultures were established from mouse embryos. Cells were exposed for 24 hours to E2 and/or P, the estrogen receptor antagonist ICI 182.780 (ICI and the progesterone receptor antagonist mifepristone (RU 486. The mRNA expression of vascular endothelial growth factor (VEGF and surfactant protein B and C (SB-B, SB-C was determined, and protein levels of VEGF were measured. Only the combined treatment with E2 and P increased mRNA expression and VEGF protein in AT-II cells and lung fibroblasts. Combined treatment also promoted SP-B and SP-C expression in AT-II cells. Pretreatment with ICI and RU 486 completely abolished the E2 and P induced effects. E2 and P enhanced expression of VEGF and surfactant proteins in primary embryonic lung cells and may be involved in regulating expression of key molecules for the prenatal lung development and postnatal lung function.

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

    Directory of Open Access Journals (Sweden)

    Jacob V Stidsen

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

  17. Surfactant Protein B 1580 Polymorphism Is Associated with Susceptibility to Chronic Obstructive Pulmonary Disease in Chinese Han Population

    Institute of Scientific and Technical Information of China (English)

    胡瑞成; 徐永健; 张珍祥

    2004-01-01

    Summary: Whether surfactant protein B (SP-B)-18A/C and 1580C/T polymorphism were associated with susceptibility to chronic obstructive pulmonary disease (COPD) in Chinese Han population was investigated. After genomic DNA was isolated from blood of COPD smokers and control smokers, the genotypes of SP-B-18A/C and SP-B1580C/T polymorphism loci were determined by polymerase chain reaction restriction fragment length polymorphism analysis (PCR-RFLP) respectively.The results showed that there was significant difference in genotypes distribution frequency of SPB1580C/T polymorphism locus between COPD smokers and control smokers. C→T mutation rate (including TT homozygote and CT heterozygote) in COPD smokers was higher than in control smokers (57.9 % vs 41.7 %, x2 =4.93, P<0.05), whereas there was no significant difference in genotypes distribution frequency of SP-B1580-18A/C locus between COPD smokers and control smokers. The allele frequency (29.1 %) of SP-B1580-18A/C locus is lower than T allele (70.9 %)in Chinese Han Population, and the distribution was different from that in Mexican, in which, the A and T allele frequencies were 85 % and 15 % respectively. It was concluded that SP-B1580 T allele was probably associated with increased susceptibility to COPD in Chinese Han population;The polymorphism of SP-B-18A/C locus maybe varied with race.

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

    Science.gov (United States)

    Zheng, Yi; Pan, Zhongli; Zhang, Ruihong; Wang, Donghai; Jenkins, Bryan

    Our previous research has shown that saline Creeping Wild Ryegrass (CWR), Leymus triticoides, has a great potential to be used for bioethanol production because of its high fermentable sugar yield, up to 85% cellulose conversion of pretreated CWR. However, the high cost of enzyme is still one of the obstacles making large-scale lignocellulosic bioethanol production economically difficult. It is desirable to use reduced enzyme loading to produce fermentable sugars with high yield and low cost. To reduce the enzyme loading, the effect of addition of non-ionic surfactants and non-catalytic protein on the enzymatic hydrolysis of pretreated CWR was investigated in this study. Tween 20, Tween 80, and bovine serum albumin (BSA) were used as additives to improve the enzymatic hydrolysis of dilute sulfuric-acid-pretreated CWR. Under the loading of 0.1 g additives/g dry solid, Tween 20 was the most effective additive, followed by Tween 80 and BSA. With the addition of Tween 20 mixed with cellulase loading of 15 FPU/g cellulose, the cellulose conversion increased 14% (from 75 to 89%), which was similar to that with cellulase loading of 30 FPU/g cellulose and without additive addition. The results of cellulase and BSA adsorption on the Avicel PH101, pretreated CWR, and lignaceous residue of pretreated CWR support the theory that the primary mechanism behind the additives is prevention of non-productive adsorption of enzymes on lignaceous material of pretreated CWR. The addition of additives could be a promising technology to improve the enzymatic hydrolysis by reducing the enzyme activity loss caused by non-productive adsorption.

  19. Expression of surfactant proteins SP-A and SP-D in murine decidua and immunomodulatory effects on decidual macrophages.

    Science.gov (United States)

    Madhukaran, Shanmuga Priyaa; Koippallil Gopalakrishnan, Aghila Rani; Pandit, Hrishikesh; Marri, Eswari Dodagatta-; Kouser, Lubna; Jamil, Kaiser; Alhamlan, Fatimah S; Kishore, Uday; Madan, Taruna

    2016-02-01

    Surfactant proteins SP-A and SP-D are pattern recognition innate immune molecules that belong to the C-type lectin family. In lungs, they play an important role in the clearance of pathogens and control of inflammation. SP-A and SP-D are also expressed in the female reproductive tract where they play an important role in pregnancy and parturition. However, the role of SP-A and SP-D expressed at the feto-maternal interface (decidua) remains unclear. Here, we have examined the expression of SP-A and SP-D in the murine decidua at 17.5 (pre-parturition) and 19.5dpc (near parturition) and their effect on lipopolysaccharide (LPS)-treated decidual macrophages. SP-A and SP-D were localized to stromal cells in the murine decidua at 17.5 and 19.5dpc in addition to cells lining the maternal spiral artery. Purified pre-parturition decidual cells were challenged with LPS with and without SP-A or SP-D, and expression of F4/80 and TNF-α were measured by flow cytometry. On their own, SP-A or SP-D did not affect the percentage of F4/80 positive cells while they suppressed the percentage of TNF-α positive cells. However, simultaneous addition of SP-A or SP-D, together with LPS, reduced TNF-α secreting F4/80 positive cells. It is likely that exogenous administration of SP-A and SP-D in decidua can potentially control infection and inflammation mediators during spontaneous term labor and infection-induced preterm labor. Thus, the presence of SP-A and SP-D in the murine decidua is likely to play a protective role against intrauterine infection during pregnancy. PMID:26421960

  20. Comparison of surfactant protein B polymorphisms of healthy term newborns with preterm newborns having respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    P.P.R. Lyra

    2007-06-01

    Full Text Available Polymorphisms and mutations in the surfactant protein B (SP-B gene have been associated with the pathogenesis of respiratory distress syndrome (RDS. The objective of the present study was to compare the frequencies of SP-B gene polymorphisms between preterm babies with RDS and healthy term newborns. We studied 50 preterm babies with RDS (inclusion criteria - newborns with RDS and gestational age between 28 and 33 weeks and 6 days, and 100 healthy term newborns. Four SP-B gene polymorphisms were analyzed: A/C at nucleotide -18, C/T at nucleotide 1580, A/G at nucleotide 9306, and G/C at nucleotide 8714, by PCR amplification of genomic DNA and genotyping by cRFLP. The healthy newborns comprised 42 female and 58 male neonates; 39 were white and 61 non-white. The RDS group comprised 21 female and 29 male preterm neonates; 28 were white and 22 non-white. Weight ranged from 640 to 2080 g (mean: 1273 g; mean gestational age was 31 weeks and 2 days (range: 28-33 weeks and 6 days. When white children were analyzed separately, a statistically significant difference in the G/C polymorphism at 8714 was observed between groups (P = 0.028. All other genotype frequencies were similar for both groups when sex and race were analyzed together. Analysis of the SP-B polymorphism G/C at nucleotide 8714 showed that among white neonates the GG genotype was found only in the RDS group at a frequency of 17% and the GC genotype was more frequently found in healthy term newborns. These data demonstrate an association of GG genotype with RDS.

  1. 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: wseum@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Choi, Soo Young, E-mail: sychoi@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of)

    2012-01-20

    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.

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

    International Nuclear Information System (INIS)

    Highlights: ► We construct a cell permeable Tat-ANX1 fusion protein. ► We examined the protective effects of Tat-ANX1 protein on OVA-induced asthma in animal models. ► Transduced Tat-ANX1 protein protects from the OVA-induced production of cytokines and eosinophils in BAL fluid. ► Tat-ANX1 protein markedly reduced OVA-induced MAPK in lung tissues. ► 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.

  3. Neutralizing inhibitors in the airways of naïve ferrets do not play a major role in modulating the virulence of H3 subtype influenza A viruses.

    Science.gov (United States)

    Job, Emma R; Pizzolla, Angela; Nebl, Thomas; Short, Kirsty R; Deng, Yi-Mo; Carolan, Louise; Laurie, Karen L; Brooks, Andrew G; Reading, Patrick C

    2016-07-01

    Many insights regarding the pathogenesis of human influenza A virus (IAV) infections have come from studies in mice and ferrets. Surfactant protein (SP)-D is the major neutralizing inhibitor of IAV in mouse airway fluids and SP-D-resistant IAV mutants show enhanced virus replication and virulence in mice. Herein, we demonstrate that sialylated glycoproteins, rather than SP-D, represent the major neutralizing inhibitors against H3 subtype viruses in airway fluids from naïve ferrets. Moreover, while resistance to neutralizing inhibitors is a critical factor in modulating virus replication and disease in the mouse model, it does not appear to be so in the ferret model, as H3 mutants resistant to either SP-D or sialylated glycoproteins in ferret airway fluids did not show enhanced virulence in ferrets. These data have important implications for our understanding of pathogenesis and immunity to human IAV infections in these two widely used animal models of infection. PMID:27110707

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

    Science.gov (United States)

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

    2016-08-01

    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. PMID:27209195

  5. Pulmonary Surfactant Surface Tension Influences Alveolar Capillary Shape and Oxygenation

    OpenAIRE

    Ikegami, Machiko; Weaver, Timothy E.; Grant, Shawn N.; Whitsett, Jeffrey A.

    2009-01-01

    Alveolar capillaries are located in close proximity to the alveolar epithelium and beneath the surfactant film. We hypothesized that the shape of alveolar capillaries and accompanying oxygenation are influenced by surfactant surface tension in the alveolus. To prove our hypothesis, surfactant surface tension was regulated by conditional expression of surfactant protein (SP)-B in Sftpb−/− mice, thereby inhibiting surface tension–lowering properties of surfactant in vivo within 24 hours after d...

  6. Stable isotope tracers to estimate lung surfactant metabolism in vivo

    OpenAIRE

    Lamonica, Giulia

    2013-01-01

    Aim of this thesis was to apply the stable isotopes technique to study pulmonary surfactant kinetics. Lung surfactant is essential to live, because it prevents the alveoli to collapse during normal breathing. Lung surfactant is composed of lipids and specific proteins, and nowadays it is well known that alterations on the composition and amount of surfactant are involved in acute and chronic lung diseases. This work presents two studies about lung surfactant kinetics. The first one i...

  7. Combined effect of synthetic protein, Mini-B, and cholesterol on a model lung surfactant mixture at the air-water interface.

    Science.gov (United States)

    Chakraborty, Aishik; Hui, Erica; Waring, Alan J; Dhar, Prajnaparamita

    2016-04-01

    The overall goal of this work is to study the combined effects of Mini-B, a 34 residue synthetic analog of the lung surfactant protein SP-B, and cholesterol, a neutral lipid, on a model binary lipid mixture containing dipalmitolphosphatidylcholine (DPPC) and palmitoyl-oleoyl-phosphatidylglycerol (POPG), that is often used to mimic the primary phospholipid composition of lung surfactants. Using surface pressure vs. mean molecular area isotherms, fluorescence imaging and analysis of lipid domain size distributions; we report on changes in the structure, function and stability of the model lipid-protein films in the presence and absence of varying composition of cholesterol. Our results indicate that at low cholesterol concentrations, Mini-B can prevent cholesterol's tendency to lower the line tension between lipid domain boundaries, while maintaining Mini-B's ability to cause reversible collapse resulting in the formation of surface associated reservoirs. Our results also show that lowering the line tension between domains can adversely impact monolayer folding mechanisms. We propose that small amounts of cholesterol and synthetic protein Mini-B can together achieve the seemingly opposing requirements of efficient LS: fluid enough to flow at the air-water interface, while being rigid enough to oppose irreversible collapse at ultra-low surface tensions. PMID:26775740

  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. Induction of regulator of G-protein signaling 2 expression by long-acting β2-adrenoceptor agonists and glucocorticoids in human airway epithelial cells.

    Science.gov (United States)

    Holden, Neil S; George, Tresa; Rider, Christopher F; Chandrasekhar, Ambika; Shah, Suharsh; Kaur, Manminder; Johnson, Malcolm; Siderovski, David P; Leigh, Richard; Giembycz, Mark A; Newton, Robert

    2014-01-01

    In asthma and chronic obstructive pulmonary disease (COPD) multiple mediators act on Gαq-linked G-protein-coupled receptors (GPCRs) to cause bronchoconstriction. However, acting on the airway epithelium, such mediators may also elicit inflammatory responses. In human bronchial epithelial BEAS-2B cells (bronchial epithelium + adenovirus 12-SV40 hybrid), regulator of G-protein signaling (RGS) 2 mRNA and protein were synergistically induced in response to combinations of long-acting β2-adrenoceptor agonist (LABA) (salmeterol, formoterol) plus glucocorticoid (dexamethasone, fluticasone propionate, budesonide). Equivalent responses occurred in primary human bronchial epithelial cells. Concentrations of glucocorticoid plus LABA required to induce RGS2 expression in BEAS-2B cells were consistent with the levels achieved therapeutically in the lungs. As RGS2 is a GTPase-activating protein that switches off Gαq, intracellular free calcium ([Ca(2+)]i) flux was used as a surrogate of responses induced by histamine, methacholine, and the thromboxane receptor agonist U46619 [(Z)-7-[(1S,4R,5R,6S)-5-[(E,3S)-3-hydroxyoct-1-enyl]-3-oxabicyclo[2.2.1]heptan-6-yl]hept-5-enoic acid]. This was significantly attenuated by salmeterol plus dexamethasone pretreatment, or RGS2 overexpression, and the protective effect of salmeterol plus dexamethasone was abolished by RGS2 RNA silencing. Although methacholine and U46619 induced interleukin-8 (IL-8) release and this was inhibited by RGS2 overexpression, the repression of U46619-induced IL-8 release by salmeterol plus dexamethasone was unaffected by RGS2 knockdown. Given a role for Gαq-mediated pathways in inducing IL-8 release, we propose that RGS2 acts redundantly with other effector processes to repress IL-8 expression. Thus, RGS2 expression is a novel effector mechanism in the airway epithelium that is induced by glucocorticoid/LABA combinations. This could contribute to the efficacy of glucocorticoid/LABA combinations in asthma and

  10. Emergency airway puncture

    Science.gov (United States)

    Emergency airway puncture is the placement of a hollow needle through the throat into the airway. It ... Emergency airway puncture is done in an emergency situation, when someone is choking and all other efforts ...

  11. 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

  12. The effect of interleukin-13 (IL-13 and interferon-γ (IFN-γ on expression of surfactant proteins in adult human alveolar type II cells in vitro

    Directory of Open Access Journals (Sweden)

    Mason Robert J

    2010-11-01

    Full Text Available Abstract Background Surfactant proteins are produced predominantly by alveolar type II (ATII cells, and the expression of these proteins can be altered by cytokines and growth factors. Th1/Th2 cytokine imbalance is suggested to be important in the pathogenesis of several adult lung diseases. Recently, we developed a culture system for maintaining differentiated adult human ATII cells. Therefore, we sought to determine the effects of IL-13 and IFN-γ on the expression of surfactant proteins in adult human ATII cells in vitro. Additional studies were done with rat ATII cells. Methods Adult human ATII cells were isolated from deidentified organ donors whose lungs were not suitable for transplantation and donated for medical research. The cells were cultured on a mixture of Matrigel and rat-tail collagen for 8 d with differentiation factors and human recombinant IL-13 or IFN-γ. Results IL-13 reduced the mRNA and protein levels of surfactant protein (SP-C, whereas IFN-γ increased the mRNA level of SP-C and proSP-C protein but not mature SP-C. Neither cytokine changed the mRNA level of SP-B but IFN-γ slightly decreased mature SP-B. IFN-γ reduced the level of the active form of cathepsin H. IL-13 also reduced the mRNA and protein levels of SP-D, whereas IFN-γ increased both mRNA and protein levels of SP-D. IL-13 did not alter SP-A, but IFN-γ slightly increased the mRNA levels of SP-A. Conclusions We demonstrated that IL-13 and IFN-γ altered the expression of surfactant proteins in human adult ATII cells in vitro. IL-13 decreased SP-C and SP-D in human ATII cells, whereas IFN-γ had the opposite effect. The protein levels of mature SP-B were decreased by IFN-γ treatment, likely due to the reduction in active form cathpesin H. Similarly, the active form of cathepsin H was relatively insufficient to fully process proSP-C as IFN-γ increased the mRNA levels for SP-C and proSP-C protein, but there was no increase in mature SP-C. These observations

  13. 应用肺表面活性物质联合NCPAP治疗早产儿呼吸窘迫综合征的对照研究%Randomized controlled trial on treatment of respiratory distress syndrome with preterm infants by pulmonary surfactant combined with nasal continuous positive airways pressure

    Institute of Scientific and Technical Information of China (English)

    刘光辉; 张健; 卢林阳

    2012-01-01

    目的 探讨应用肺表面活性物质(PS)联合NCPAP治疗早产儿呼吸窘迫综合征(RDS)的效果.方法 将82例呼吸窘迫综合征的早产儿随机分为两组,观察组早期给予气管滴注肺表面活性物质,随后立即进行NCPAP治疗;对照组不予肺表面活性物质处理,比较两组患儿治疗效果、住院时间、氧疗时间、机械通气使用以及并发症等情况.结果 两组患儿治疗后血气结果较治疗前有显著改善,差异有统计学意义(P<0.05);观察组患儿的机械通气使用情况、呼吸机相关肺炎的发生率、氧疗时间以及住院时间均较对照组低,差异有统计学意义(P<0.05).结论 早期应用PS联合NCPAP是治疗早产儿RDS的有效方式,能快速有效地改善肺功能,缩短氧疗时间及住院时间,减少相关并发症的发生.%Objective To evaluate the therapeutic effect of pulmonary surfactant administration combined with nasal continuous positive airways pressure in preterrn infants with neonatal respiratory distress syndrome (NRDS). Methods A randomized control trial was conducted in 82 preterm infants with NRDS, which were randomized to the observation group ( received pulmonary surfactant combined with NCPAP) and control group (without pulmonary surfactant). Treatment effect and group comparisons were made on the measures of days of staying in the intensive care unit, time receiving oxygen therapy, undergoing mechanical ventilation and complication. Results Blood gas improved significantly after treatment in the two groups (P < 0. 05). The need for mechanical ventilation, incidence of ventilato-rassociated pneumonia , time receiving oxygen therapy, and days of staying in the intensive care unit were less in the observation group than those in the control group ( P < 0. 05). Conclusions The early application of NCPAP after pulmonary surfactant administration for preterm infants with RDS is beneficial to improve therapeutic effect.

  14. 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.

    Directory of Open Access Journals (Sweden)

    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.

  15.  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)

    Sørensen, Grith Lykke; Hjelmborg, Jacob v. B.; Leth-Larsen, Rikke;

    2006-01-01

    Surfactant protein D (SP-D) is a key regulator of pathogen-induced inflammation. SP-D is further involved in lipid homeostasis in mouse lung and circulation and recent data have demonstrated that the body mass index (BMI; in kg/m(2)) is influenced by genes in common with SP-D. The objective of th...... 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.......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 the...... present study was to describe the association between serum SP-D and weight, waist circumference or BMI, and furthermore to observe body weight development in SP-D-deficient (Spd-/-) mice. As a part of the Danish population-based twin study (GEMINAKAR) on the metabolic syndrome, we analysed 1476 Danish...

  16. Surfactant protein D of the innate immune defence is inversely associated with human obesity and SP-D deficiency infers increased body weight in mice

    DEFF Research Database (Denmark)

    Sorensen, G L; Hjelmborg, J V B; Leth-Larsen, R;

    2006-01-01

    Surfactant protein D (SP-D) is a key regulator of pathogen-induced inflammation. SP-D is further involved in lipid homeostasis in mouse lung and circulation and recent data have demonstrated that the body mass index (BMI; in kg/m(2)) is influenced by genes in common with SP-D. The objective of th...... 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.......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 the...... present study was to describe the association between serum SP-D and weight, waist circumference or BMI, and furthermore to observe body weight development in SP-D-deficient (Spd-/-) mice. As a part of the Danish population-based twin study (GEMINAKAR) on the metabolic syndrome, we analysed 1476 Danish...

  17. Sequences of a hairpin structure in the 3'-untranslated region mediate regulation of human pulmonary surfactant protein B mRNA stability.

    Science.gov (United States)

    Huang, Helen W; Payne, David E; Bi, Weizhen; Pan, Su; Bruce, Shirley R; Alcorn, Joseph L

    2012-05-15

    The ability of pulmonary surfactant to reduce alveolar surface tension requires adequate expression of surfactant protein B (SP-B). Dexamethasone (DEX, 10(-7) M) increases human SP-B mRNA stability by a mechanism that requires a 126-nt-long segment (the 7.6S region) of the 3'-untranslated region (3'-UTR). The objective of this study was to identify sequences in the 7.6S region that mediate regulation of SP-B mRNA stability. The 7.6S region was found to be sufficient for DEX-mediated stabilization of mRNA. Sequential substitution mutagenesis of the 7.6S region indicates that a 90-nt region is required for DEX-mediated stabilization and maintenance of intrinsic stability. In this region, one 30-nt-long element (002), predicted to form a stem-loop structure, is sufficient for DEX-mediated stabilization of mRNA and intrinsic mRNA stability. Cytosolic proteins specifically bind element 002, and binding activity is unaffected whether proteins are isolated from cells incubated in the absence or presence of DEX. While loop sequences of element 002 have no role in regulation of SP-B mRNA stability, the proximal stem sequences are required for DEX-mediated stabilization and specific binding of proteins. Mutation of the sequences that comprise the proximal or distal arm of the stem negates the destabilizing activity of element 002 on intrinsic SP-B mRNA stability. These results indicate that cytosolic proteins bind a single hairpin structure that mediates intrinsic and hormonal regulation of SP-B mRNA stability via mechanisms that involve sequences of the stems of the hairpin structure. PMID:22367784

  18. Endotoxin-induced nitric oxide production rescues airway growth and maturation in atrophic fetal rat lung explants

    International Nuclear Information System (INIS)

    Inflammation induces premature maturation of the fetal lung but the signals causing this effect remain unclear. We determined if nitric oxide (NO) synthesis, evoked by Escherichia coli lipopolysaccharide (LPS, 2 μg ml-1), participated in this process. Fetal rat lung airway surface complexity rose 2.5-fold over 96 h in response to LPS and was associated with increased iNOS protein expression and activity. iNOS inhibition by N6-(1-iminoethyl)-L-lysine-2HCl (L-NIL) abolished this and induced airway atrophy similar to untreated explants. Surfactant protein-C (SP-C) expression was also induced by LPS and abolished by L-NIL. As TGFβ suppresses iNOS activity, we determined if feedback regulation modulated NO-dependent maturation. LPS induced TGFβ1 release and SMAD4 nuclear translocation 96 h after treatment. Treatment of explants with a blocking antibody against TGFβ1 sustained NO production and airway morphogenesis whereas recombinant TGFβ1 antagonized these effects. Feedback regulation of NO synthesis by TGFβ may, thus, modulate airway branching and maturation of the fetal lung

  19. The role of surfactant protein A and B genes in heritable susceptibility to neonatal respiratory distress syndrome

    OpenAIRE

    Haataja, R.

    2001-01-01

    Abstract Respiratory distress syndrome (RDS) is a disease characterized by neonatal respiratory failure. It is principally caused by a deficiency of pulmonary surfactant, which is a lipoprotein mixture essential for reducing surface tension at the air-liquid interface of the alveolus. Prematurity is the major risk factor predisposing to RDS. Several pieces of evidence suggest the role of genetic factors in the susceptibility to this multifactorial disease. The pres...

  20. A small key unlocks a heavy door: The essential function of the small hydrophobic proteins SP-B and SP-C to trigger adsorption of pulmonary surfactant lamellar bodies.

    Science.gov (United States)

    Hobi, Nina; Giolai, Michael; Olmeda, Bárbara; Miklavc, Pika; Felder, Edward; Walther, Paul; Dietl, Paul; Frick, Manfred; Pérez-Gil, Jesus; Haller, Thomas

    2016-08-01

    The molecular basis involving adsorption of pulmonary surfactant at the respiratory air-liquid interface and the specific roles of the surfactant proteins SP-B and SP-C in this process have not been completely resolved. The reasons might be found in the largely unknown structural assembly in which surfactant lipids and proteins are released from alveolar type II cells, and the difficulties to sample, manipulate and visualize the adsorption of these micron-sized particles at an air-liquid interface under appropriate physiological conditions. Here, we introduce several approaches to overcome these problems. First, by immunofluorescence we could demonstrate the presence of SP-B and SP-C on the surface of exocytosed surfactant particles. Second, by sampling the released particles and probing their adsorptive capacity we could demonstrate a remarkably high rate of interfacial adsorption, whose rate and extent was dramatically affected by treatment with antibodies against SP-B and SP-C. The effect of both antibodies was additive and specific. Third, direct microscopy of an inverted air-liquid interface revealed that the blocking effect is due to a stabilization of the released particles when contacting the air-liquid interface, precluding their transformation and the formation of surface films. We conclude that SP-B and SP-C are acting as essential, preformed molecular keys in the initial stages of surfactant unpacking and surface film formation. We further propose that surfactant activation might be transduced by a conformational change of the surfactant proteins upon contact with surface forces acting on the air-liquid interface. PMID:27155084

  1. Lung surfactant in subacute pulmonary disease

    OpenAIRE

    Spragg Roger G; Devendra Gehan

    2002-01-01

    Abstract Pulmonary surfactant is a surface active material composed of both lipids and proteins that is produced by alveolar type II pneumocytes. Abnormalities of surfactant in the immature lung or in the acutely inflamed mature lung are well described. However, in a variety of subacute diseases of the mature lung, abnormalities of lung surfactant may also be of importance. These diseases include chronic obstructive pulmonary disease, asthma, cystic fibrosis, interstitial lung disease, pneumo...

  2. The Molecular Era of Surfactant Biology

    OpenAIRE

    Jeffrey A Whitsett

    2014-01-01

    Advances in the physiology, biochemistry, molecular and cell biology of the pulmonary surfactant system transformed the clinical care and outcome of preterm infants with respiratory distress syndrome. The molecular era of surfactant biology provided genetic insights into the pathogenesis of pulmonary disorders, previously termed “idiopathic” that affect newborn infants, children and adults. Knowledge related to the structure and function of the surfactant proteins and their roles in alveolar ...

  3. Surfactant therapy in late preterm infants

    OpenAIRE

    Murat Yurdakök

    2013-01-01

    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 ...

  4. Airway management in trauma

    Directory of Open Access Journals (Sweden)

    Rashid M Khan

    2011-01-01

    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.

  5. Positive end-expiratory pressure and surfactant decrease lung injury during initiation of ventilation in fetal sheep

    OpenAIRE

    Hillman, Noah H.; Nitsos, Ilias; Berry, Clare; Jane Pillow, J.; Suhas G Kallapur; Alan H Jobe

    2011-01-01

    The initiation of ventilation in preterm, surfactant-deficient sheep without positive end-expiratory pressure (PEEP) causes airway injury and lung inflammation. We hypothesized that PEEP and surfactant treatment would decrease the lung injury from initiation of ventilation with high tidal volumes. Fetal sheep at 128-day gestational age were randomized to ventilation with: 1) no PEEP, no surfactant; 2) 8-cmH2O PEEP, no surfactant; 3) no PEEP + surfactant; 4) 8-cmH2O PEEP + surfactant; or 5) co...

  6. Experimental Study on How Human Lung Surfactant Protein SP-B1-25 is Oxidized by Ozone in the Presence of Fe(II) and Ascorbic Acid

    Science.gov (United States)

    Colussi, A. J.; Enami, S.; Hoffmann, M. R.

    2014-12-01

    We will report the results of experiments on the chemical fate of the human lung surfactant protein SP-B1-25 upon exposure to gaseous ozone in realistic aqueous media simulating the conditions prevalent in epithelial lining fluids in polluted ambient air. Our experiments consist of exposing aqueous microjets containing SP-B1-25, the natural antioxidant ascorbic acid, and the Fe2+ carried by most atmospheric fine particulates, under mild acidic conditions, such as those created by the innate lung host defense response. Reactants and the products of such interactions are detected via online electrospray ionization mass spectrometry. We will show that ascorbic acid largely inhibits the ozonation of SP-B1-25 in the absence of Fe2+, leading to the formation of an ascorbic acid ozonide (Enami et al., PNAS 2008). In the presence of Fe2+, however, the ozonide decomposes into reactive intermediates that result in the partial oxidation of SP-B1-25, presumable affecting its function as surfactant. We infer that these experimental results establish a plausible causal link for the observed synergic adverse health effects of ambient ozone and fine particulates

  7. Absorption-enhancing effects of gemini surfactant on the intestinal absorption of poorly absorbed hydrophilic drugs including peptide and protein drugs in rats.

    Science.gov (United States)

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

    2016-02-29

    In general, the intestinal absorption of small hydrophilic molecules and macromolecules like peptides, after oral administration is very poor. Absorption enhancers are considered to be one of the most promising agents to enhance the intestinal absorption of drugs. In this research, we focused on a gemini surfactant, a new type of absorption enhancer. The intestinal absorption of drugs, with or without sodium dilauramidoglutamide lysine (SLG-30), a gemini surfactant, was examined by an in situ closed-loop method in rats. The intestinal absorption of 5(6)-carboxyfluorescein (CF) and fluorescein isothiocyanate-dextrans (FDs) was significantly enhanced in the presence of SLG-30, such effect being reversible. Furthermore, the calcium levels in the plasma significantly decreased when calcitonin was co-administered with SLG-30, suggestive of the increased intestinal absorption of calcitonin. In addition, no significant increase in the of lactate dehydrogenase (LDH) activity or in protein release from the intestinal epithelium was observed in the presence of SLG-30, suggestive of the safety of this compound. These findings indicate that SLG-30 is an effective absorption-enhancer for improving the intestinal absorption of poorly absorbed drugs, without causing serious damage to the intestinal epithelium. PMID:26707414

  8. Prediction markers for respiratory distress syndrome: evaluation of the stable microbubble test, surfactant protein-A and hepatocyte growth factor levels in amniotic fluid.

    Directory of Open Access Journals (Sweden)

    Kumazawa K

    2003-02-01

    Full Text Available Surfactant treatment in infants with respiratory distress syndrome (RDS has decreased neonatal mortality. With the advent of this therapy, it has become important to predict accurately the fetal lung maturity of a fetus before delivery. We evaluated the stable microbubble test (SMT, surfactant protein-A (SP-A and hepatocyte growth factor (HGF in amniotic fluid as predicting markers for RDS. Of 55 amniotic fluid samples obtained by amniocentesis from women less than 37 weeks pregnant, the SMT values were as follows: sensitivity 76.5%, specificity 84.2%, positive predictive value 68.4%, negative predictive value 88.9% and overall accuracy 81.8%. For SP-A, the values were 88.2%, 65.8%, 53.6%, 92.6% and 72.7%, respectively. If we used both SMT and SP-A, we could diagnose with 100% accuracy that a case with measurements of SMT > or = 2 and SP-A > or = 420 ng/ml would not complicate with RDS (24/24. However, the RDS diagnostic accuracy of HGF does not equal to those of SMT and SP-A levels. We concluded that the rapidity, simplicity and reliability of SMT was very useful during 24-36 weeks of gestation as a bedside procedure to predict fetuses likely to develop RDS. We also noted the additive effect of SP-A in improving the accuracy of lung maturity diagnosis.

  9. Nanoparticles in the lung and their protein corona: the few proteins that count.

    Science.gov (United States)

    Whitwell, Harry; Mackay, Rose-Marie; Elgy, Christine; Morgan, Cliff; Griffiths, Mark; Clark, Howard; Skipp, Paul; Madsen, Jens

    2016-11-01

    The formation of protein coronae on nanoparticles (NPs) has been investigated almost exclusively in serum, despite the prevailing route of exposure being inhalation of airborne particles. In addition, an increasing number of nanomedicines, that exploit the airways as the site of delivery, are undergoing medical trials. An understanding of the effects of NPs on the airways is therefore required. To further this field, we have described the corona formed on polystyrene (PS) particles with different surface modifications and on titanium dioxide particles when incubated in human bronchoalveolar lavage fluid (BALF) from patients with pulmonary alveolar proteinosis (PAP). We show, using high-resolution quantitative mass spectrometry (MS(E)), that a large number of proteins bind with low copy numbers but that a few "core" proteins bind to all particles tested with high fidelity, averaging the surface properties of the different particles independent of the surface properties of the specific particle. The averaging effect at the particle surface means that differing cellular effects may not be due to the protein corona but due to the surface properties of the nanoparticle once inside the cell. Finally, the adherence of surfactant associated proteins (SP-A, B and D) suggests that there may be interactions with lipids and pulmonary surfactant (PSf), which could have potential in vivo health effects for people with chronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), or those who have increased susceptibility toward other respiratory diseases. PMID:27465202

  10. Effect of a bovine lung surfactant protein isolate (SP-B/C) on egg phosphatidylglycerol acyl chain order in a lipid mixture with dipalmitoylphosphatidylcholine and palmitic acid.

    Science.gov (United States)

    Krill, S L; Gupta, S L

    1994-04-01

    Dynamic surface tension measurements of films of a d62 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine:L-alpha-phosphatidyl-DL - glycerol:d31 palmitic acid (d62-DPPC:EggPG:d31-PA) lipid matrix in the presence of a bovine pulmonary surfactant protein isolate (SP-B/C) demonstrate the improved surface activity over that of the lipids alone. Thus, significant interaction of the proteins with the lipid matrix is demonstrated. The effect of SP-B/C on the acyl chain order of the negatively charged EggPG within a d62-DPPC:EggPG:d31-PA lipid matrix in D2O saline was investigated in thermal perturbation Fourier transform IR spectroscopic studies. The EggPG thermotropic phase behavior was determined independently of the other lipid components with perdeuterated lipids and D2O. The data demonstrate the high degree of EggPG acyl chain disorder in the absence of the protein isolate. A broad transition occurs between 30 and 40 degrees C. The addition of the protein isolate did not alter the acyl chain order at 0.281 and 1.46 mg/mL of protein. However, alterations in the lipid carbonyl vibrational mode were observed. PMID:8046609

  11. Lung surfactant in subacute pulmonary disease

    Directory of Open Access Journals (Sweden)

    Spragg Roger G

    2002-04-01

    Full Text Available Abstract Pulmonary surfactant is a surface active material composed of both lipids and proteins that is produced by alveolar type II pneumocytes. Abnormalities of surfactant in the immature lung or in the acutely inflamed mature lung are well described. However, in a variety of subacute diseases of the mature lung, abnormalities of lung surfactant may also be of importance. These diseases include chronic obstructive pulmonary disease, asthma, cystic fibrosis, interstitial lung disease, pneumonia, and alveolar proteinosis. Understanding of the mechanisms that disturb the lung surfactant system may lead to novel rational therapies for these diseases.

  12. In vitro effect of meconium on the physical surface properties and morphology of exogenous pulmonary surfactant.

    OpenAIRE

    Park, K. H.; Bae, C. W.; Chung, S. J.

    1996-01-01

    The pathophysiology of meconium aspiration syndrome(MAS) is related to mechanical obstruction of the airways and to chemical pneumonitis. Meconium is also suggested to cause functional deterioration of pulmonary surfactant. Recent studies have reported that meconium inhibits the physical surface properties of pulmonary surfactant, and that administration of exogenous surfactant may provide therapeutic benefits in animal models or infants with respiratory distress due to MAS. To assess the eff...

  13. Quasi-Immiscible Spreading of Aqueous Surfactant Solutions on Entangled Aqueous Polymer Solution Subphases

    OpenAIRE

    Sharma, Ramankur; Corcoran, Timothy E.; Garoff, Stephen; Przybycien, Todd M.; Swanson, Ellen R.; Tilton, Robert D.

    2013-01-01

    Motivated by the possibility of enhancing aerosol drug delivery to mucus-obstructed lungs, the spreading of a drop of aqueous surfactant solution on a physically entangled aqueous poly(acrylamide) solution subphase that mimics lung airway surface liquid was investigated. Sodium dodecyl sulfate was used as the surfactant. To visualize spreading of the drop and mimic the inclusion of a drug substance, fluorescein, a hydrophilic and non-surface active dye, was added to the surfactant solution. T...

  14. Use of therapeutic surfactant lavage in a preterm infant with massive pulmonary hemorrhage

    OpenAIRE

    Ino Kanavaki; Laszlo Vutskits; Rimensberger, Peter C

    2012-01-01

    We report a case of a premature infant presenting with recurrent pulmonary hemorrhage in which we performed a therapeutic lavage with diluted surfactant after an acute episode of bleeding with severe intractable hypoxemia. Repeated small aliquots of diluted surfactant (10x2 mL) allowed rapid improvement in oxygenation and reduction of required mean airway pressures during high frequency oscillatory ventilation. This observation may suggest that surfactant lavage could be beneficial in massive...

  15. Pharmacogenetics, pharmacogenomics and airway disease

    Directory of Open Access Journals (Sweden)

    Hall Ian P

    2001-11-01

    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.

  16. Airway Gland Structure and Function.

    Science.gov (United States)

    Widdicombe, Jonathan H; Wine, Jeffrey J

    2015-10-01

    Submucosal glands contribute to airway surface liquid (ASL), a film that protects all airway surfaces. Glandular mucus comprises electrolytes, water, the gel-forming mucin MUC5B, and hundreds of different proteins with diverse protective functions. Gland volume per unit area of mucosal surface correlates positively with impaction rate of inhaled particles. In human main bronchi, the volume of the glands is ∼ 50 times that of surface goblet cells, but the glands diminish in size and frequency distally. ASL and its trapped particles are removed from the airways by mucociliary transport. Airway glands have a tubuloacinar structure, with a single terminal duct, a nonciliated collecting duct, then branching secretory tubules lined with mucous cells and ending in serous acini. They allow for a massive increase in numbers of mucus-producing cells without replacing surface ciliated cells. Active secretion of Cl(-) and HCO3 (-) by serous cells produces most of the fluid of gland secretions. Glands are densely innervated by tonically active, mutually excitatory airway intrinsic neurons. Most gland mucus is secreted constitutively in vivo, with large, transient increases produced by emergency reflex drive from the vagus. Elevations of [cAMP]i and [Ca(2+)]i coordinate electrolyte and macromolecular secretion and probably occur together for baseline activity in vivo, with cholinergic elevation of [Ca(2+)]i being mainly responsive for transient increases in secretion. Altered submucosal gland function contributes to the pathology of all obstructive diseases, but is an early stage of pathogenesis only in cystic fibrosis. PMID:26336032

  17. Analysis of Therapeutic Effect of Calf Pulmonary Surfactant for Injection Combined with Nasal Continuous Positive Airway Pressure on Premature Infants with Respiratory Distress Syndrome%肺表面活性剂联合持续气道正压通气治疗新生儿呼吸窘迫综合征疗效观察

    Institute of Scientific and Technical Information of China (English)

    葛标; 张翔

    2013-01-01

    目的:观察注射用牛肺表面活性剂(珂立苏)联合鼻塞持续气道正压通气(nCPAP)治疗新生儿呼吸窘迫综合征(NRDS)的疗效.方法:选取2009年6月至2012年6月太和县中医院新生儿科收治的NRDS患儿60例,随机分为治疗组和对照组各30例.治疗组经气管内滴入牛肺表面活性剂后拔管给予nCPAP支持治疗,对照组单纯应用nCPAP支持治疗,比较两组患儿治疗24h后的疗效及治疗前后的血气分析、X线胸片情况.结果:治疗24h后,治疗组总有效率86.66%,对照组70.00%,两组比较差异有统计学意义(P<0.05);治疗1h、12h、24h后,治疗组血气分析指标均好于对照组(P均<0.05).结论:注射用牛肺表面活性剂联合nCPAP治疗NRDS疗效确切,可提高抢救成功率.%Objective:To observe the effect of calf pulmonary surfactant for injection combined with nasal continuous positive airway pressure (nCPAP) in the treatment of neonatal respiratory distress syndrome (NRDS).Methods:Thirty cases in the treatment group were given calf pulmonary surfactant for injection by intratracheal instillation,and then followed by nasal continuous positive airway pressure(nCPAP).30 cases in the control group were only treated by nCPAP.Clinical effects,blood gas analysis and chest X-ray changes before and after treatment were compared.Results:The clinical effect of the treatment group was better than that of the control group.The total effective rate of the treatment group (86.66%) was significantly higher than that of the control group (70.00%) after treatment for 24 hours (P<0.05).Blood gas analysis result was improved markedly at the time of 1,12,24 hours after treatment in the treatment group; there were significant differences between the two groups (P<0.05).Conclusions:The application of calf pulmonary surfactant for injection combined with nCPAP in the treatment of NRDS has good effects and raises the rescue success rate significantly.

  18. μ-PIV/Shadowgraphy measurements to elucidate dynamic physicochemical interactions in a multiphase model of pulmonary airway reopening

    Science.gov (United States)

    Yamaguchi, Eiichiro

    2010-10-01

    We employ micro-particle image velocimetry (μ-PIV) and shadowgraphy to measure the ensemble-averaged fluid-phase velocity field and interfacial geometry during pulsatile bubble propagation that includes a reverse-flow phase under influence of exogenous lung surfactant (Infasurf). Disease states such as respiratory distress syndrome (RDS) are characterized by insufficient pulmonary surfactant concentrations that enhance airway occlusion and collapse. Subsequent airway reopening, driven by mechanical ventilation, may generate damaging stresses that cause ventilator-induced lung injury (VILI). It is hypothesized that reverse flow may enhance surfactant uptake and protect the lung from VILI. The microscale observations conducted in this study will provide us with a significant understanding of dynamic physicochemical interactions that can be manipulated to reduce the magnitude of this damaging mechanical stimulus during airway reopening. Bubble propagation through a liquid-occluded fused glass capillary tube is controlled by linear-motor-driven syringe pumps that provide mean and sinusoidal velocity components. A translating microscope stage mechanically subtracts the mean velocity of the bubble tip in order to hold the progressing bubble tip in the microscope field of view. To optimize the signal-to-noise ratio near the bubble tip, μ-PIV and shadow images are recorded in separate trials then combined during post-processing with help of a custom-designed micro scale marker. Non-specific binding of Infasurf proteins to the channel wall is controlled by oxidation and chemical treatment of the glass surface. The colloidal stability and dynamic/static surface properties of the Infasurf-PIV particle solution are carefully adjusted based on Langmuir trough measurements. The Finite Time Lyapunov Exponent (FTLE) is computed to provide a Lagrangian perspective for comparison with our boundary element predictions.

  19. Protective Effects of Surfactant Protein D (SP-D) Treatment in 1,3-β-glucan-modulated Allergic Inflammation

    DEFF Research Database (Denmark)

    Fakih, Dalia; Pilecki, Bartosz; Schlosser, Anders;

    2015-01-01

    -γ production. rfhSP-D treatment further reduced mucous metaplasia and Th2 cytokine secretion to background levels. In summary, rfhSP-D treatment resulted in attenuation of both allergic inflammation and 1,3-β-glucan mediated neutrophilic inflammation. Our data suggest that treatment with high dose SP......SP-D is a pulmonary collectin important in lung immunity. SP-D-deficient mice (Sftpd(-/-)) are reported to be susceptible to ovalbumin (OVA)- and fungal allergen-induced pulmonary inflammation, while treatment with exogenous SP-D has therapeutic effects in such disease models. β-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...

  20. Surfactant administration in neonates: A review of delivery methods.

    Science.gov (United States)

    Nouraeyan, Nina; Lambrinakos-Raymond, Alicia; Leone, Marisa; Sant'Anna, Guilherme

    2014-01-01

    Surfactant has revolutionized the treatment of respiratory distress syndrome and some other respiratory conditions that affect the fragile neonatal lung. Despite its widespread use, the optimal method of surfactant administration in preterm infants has yet to be clearly determined. The present article reviews several aspects of administration techniques that can influence surfactant delivery into the pulmonary airways: the bolus volume, injection rate, gravity and orientation, ventilation strategies, alveolar recruitment, and viscosity and surface tension of the fluid instilled. Based on the present review, knowledge gaps regarding the best way to administer surfactant to neonates remain. From the available evidence, however, the most effective way to optimize surfactant delivery and obtain a more homogeneous distribution of the drug is by using rapid bolus instillation in combination with appropriate alveolar recruitment techniques. PMID:26078618

  1. Surfactant abnormalities in infants with severe viral bronchiolitis.

    OpenAIRE

    Dargaville, P A; South, M; McDougall, P N

    1996-01-01

    To determine whether abnormalities of pulmonary surfactant occur in infants with acute viral bronchiolitis, surfactant indices were measured in lung lavage fluid from 12 infants with severe bronchiolitis and eight infants without lung disease. Compared with controls, the bronchiolitis group showed deficiency of surfactant protein A (1.02 v 14.4 micrograms/ml) and disaturated phosphatidylcholine (35 v 1060 micrograms/ml) which resolved as the disease improved. Surfactant functional activity wa...

  2. Pulmonary surfactants and their role in pathophysiology of lung disorders.

    Science.gov (United States)

    Akella, Aparna; Deshpande, Shripad B

    2013-01-01

    Surfactant is an agent that decreases the surface tension between two media. The surface tension between gaseous-aqueous interphase in the lungs is decreased by the presence of a thin layer of fluid known as pulmonary surfactant. The pulmonary surfactant is produced by the alveolar type-II (AT-II) cells of the lungs. It is essential for efficient exchange of gases and for maintaining the structural integrity of alveoli. Surfactant is a secretory product, composed of lipids and proteins. Phosphatidylcholine and phosphatidylglycerol are the major lipid constituents and SP-A, SP-B, SP-C, SP-D are four types of surfactant associated proteins. The lipid and protein components are synthesized separately and are packaged into the lamellar bodies in the AT-II cells. Lamellar bodies are the main organelle for the synthesis and metabolism of surfactants. The synthesis, secretion and recycling of the surfactant lipids and proteins is regulated by complex genetic and metabolic mechanisms. The lipid-protein interaction is very important for the structural organization of surfactant monolayer and its functioning. Alterations in surfactant homeostasis or biophysical properties can result in surfactant insufficiency which may be responsible for diseases like respiratory distress syndrome, lung proteinosis, interstitial lung diseases and chronic lung diseases. The biochemical, physiological, developmental and clinical aspects of pulmonary surfactant are presented in this article to understand the pathophysiological mechanisms of these diseases. PMID:23441475

  3. Acute chlorine gas exposure produces transient inflammation and a progressive alteration in surfactant composition with accompanying mechanical dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Massa, Christopher B.; Scott, Pamela; Abramova, Elena; Gardner, Carol; Laskin, Debra L.; Gow, Andrew J., E-mail: Gow@rci.rutgers.edu

    2014-07-01

    Acute Cl{sub 2} exposure following industrial accidents or military/terrorist activity causes pulmonary injury and severe acute respiratory distress. Prior studies suggest that antioxidant depletion is important in producing dysfunction, however a pathophysiologic mechanism has not been elucidated. We propose that acute Cl{sub 2} inhalation leads to oxidative modification of lung lining fluid, producing surfactant inactivation, inflammation and mechanical respiratory dysfunction at the organ level. C57BL/6J mice underwent whole-body exposure to an effective 60 ppm-hour Cl{sub 2} dose, and were euthanized 3, 24 and 48 h later. Whereas pulmonary architecture and endothelial barrier function were preserved, transient neutrophilia, peaking at 24 h, was noted. Increased expression of ARG1, CCL2, RETLNA, IL-1b, and PTGS2 genes was observed in bronchoalveolar lavage (BAL) cells with peak change in all genes at 24 h. Cl{sub 2} exposure had no effect on NOS2 mRNA or iNOS protein expression, nor on BAL NO{sub 3}{sup −} or NO{sub 2}{sup −}. Expression of the alternative macrophage activation markers, Relm-α and mannose receptor was increased in alveolar macrophages and pulmonary epithelium. Capillary surfactometry demonstrated impaired surfactant function, and altered BAL phospholipid and surfactant protein content following exposure. Organ level respiratory function was assessed by forced oscillation technique at 5 end expiratory pressures. Cl{sub 2} exposure had no significant effect on either airway or tissue resistance. Pulmonary elastance was elevated with time following exposure and demonstrated PEEP refractory derecruitment at 48 h, despite waning inflammation. These data support a role for surfactant inactivation as a physiologic mechanism underlying respiratory dysfunction following Cl{sub 2} inhalation. - Highlights: • Effect of 60 ppm*hr Cl{sub 2} gas on lung inflammation and mechanical function examined. • Pulmonary inflammation is transient and minor.

  4. Transforming Growth Factor-β Induces Airway Smooth Muscle Hypertrophy

    OpenAIRE

    Goldsmith, Adam M.; Bentley, J. Kelley; Zhou, Limei; Jia, Yue; Bitar, Khalil N; Fingar, Diane C.; Hershenson, Marc B.

    2005-01-01

    Although smooth muscle hypertrophy is present in asthmatic airways, little is known about the biochemical pathways regulating airway smooth muscle protein synthesis, cell size, or accumulation of contractile apparatus proteins. We sought to develop a model of airway smooth muscle hypertrophy in primary cells using a physiologically relevant stimulus. We hypothesized that transforming growth factor (TGF)-β induces hypertrophy in primary bronchial smooth muscle cells. Primary human bronchial sm...

  5. The influence of surfactant on the propagation of a semi-infinite bubble through a liquid-filled compliant channel

    OpenAIRE

    Halpern, David; Gaver, Donald P.

    2012-01-01

    We investigate the influence of a soluble surfactant on the steady-state motion of a finger of air through a compliant channel. This study provides a basic model from which to understand the fluid–structure interactions and physicochemical hydrodynamics of pulmonary airway reopening. Airway closure occurs in lung diseases such as respiratory distress syndrome and acute respiratory distress syndrome as a result of fluid accumulation and surfactant insufficiency. This results in ‘compliant coll...

  6. Abnormal SDS-PAGE migration of cytosolic proteins can identify domains and mechanisms that control surfactant binding

    OpenAIRE

    Shi, Yunhua; Mowery, Richard A; Ashley, Jonathan; Hentz, Michelle; Ramirez, Alejandro J; Bilgicer, Basar; Slunt-Brown, Hilda; David R Borchelt; Bryan F Shaw

    2012-01-01

    The amino acid substitution or post-translational modification of a cytosolic protein can cause unpredictable changes to its electrophoretic mobility during SDS-PAGE. This type of “gel shifting” has perplexed biochemists and biologists for decades. We identify a mechanism for “gel shifting” that predominates among a set of ALS (amyotrophic lateral sclerosis) mutant hSOD1 (superoxide dismutase) proteins, post-translationally modified hSOD1 proteins, and homologous SOD1 proteins from different ...

  7. 经鼻持续气道正压通气联合肺表面活性物质治疗新生儿呼吸窘迫综合征%Therapeutics of neonatal respiratory distress syndrome with nasal continuous positive airways pressure combined with pulmonary surfactant

    Institute of Scientific and Technical Information of China (English)

    王朝海; 魏光宇; 马荣伟

    2010-01-01

    目的 探讨经鼻持续气道正压通气联合肺表面活性物质治疗新生儿呼吸窘迫综合征的效果.方法 <32周的早产儿合并新生儿呼吸窘迫综合征早产儿33例随机分入2组进行对照研究:应用肺表面活性物质后立即拔管继以经鼻持续气道正压通气(S-N组)16例和应用肺表面活性物质后接受机械通气治疗(S-M组)17例.比较2组主要终点和次要终点是否需要机械通气及通气时间,以及其他相关临床特征.结果 生后7 d时,S-N组有1例(6.25%)接受机械通气,S-M组有8例(47.00%)仍不能脱离呼吸机.S-M组与S-N组相比较,用氧时间[(11.4±4.6)d与(7.0±1.9)d]、经鼻持续气道正压通气时间[(6.5±2.9)d与(3.5±2.3)d)]、机械通气时间[(5.9±3.3)d与(2.2±1.2)d]、重症监护室住院时间[(29.9±8.0)d与(21.7±10.1)d]、再次使用肺表面活性物质的概率[(12.5%,2/16)与(53.0%,9/17)],S-M组均显著高于S-N组,差异有统计学意义(P均<0.05).结论 应用肺表面活性物质后立即继以经鼻持续气道正压通气有利于新生儿呼吸窘迫综合征的治疗.%Objective To evaluate the clinical effects of nasal continuous positive airway pressure (NC-PAP) and surfactant administration in preterm infants with neonatal respiratory distress syndrome(NRDS) Methods A prospective randomized study was conducted, in which infants <32 weeks' gestation with NRDS were random-ized to the aurfactant-NCPAP (S-N) group or the surfactant-mechanical ventialtion (S-M) group. Results At 7 days after birth, 1 infant (6.25%) in the S-N group and 8 infants (47.00%) in the S-M group were still undergo-ing mechanical ventilation. The duration of oxygen therapy, NCPAP and mechanical ventilation,the need for a sec-ond dose of surfactant, and the days of staying in the intensive care unit were significantly greater in the S-M group. Conclusions The immediate application of NCPAP after surfactant administration for infants with NRDS is safe and beneficial.

  8. Upper airway test (image)

    Science.gov (United States)

    An upper airway biopsy is obtained by using a flexible scope called a bronchoscope. The scope is passed down through ... may be performed when an abnormality of the upper airway is suspected. It may also be performed as ...

  9. Pulmonary surfactant coating of multi-walled carbon nanotubes (MWCNTs influences their oxidative and pro-inflammatory potential in vitro

    Directory of Open Access Journals (Sweden)

    Gasser Michael

    2012-05-01

    Full Text Available Abstract Background Increasing concern has been expressed regarding the potential adverse health effects that may be associated with human exposure to inhaled multi-walled carbon nanotubes (MWCNTs. Thus it is imperative that an understanding as to the underlying mechanisms and the identification of the key factors involved in adverse effects are gained. In the alveoli, MWCNTs first interact with the pulmonary surfactant. At this interface, proteins and lipids of the pulmonary surfactant bind to MWCNTs, affecting their surface characteristics. Aim of the present study was to investigate if the pre-coating of MWCNTs with pulmonary surfactant has an influence on potential adverse effects, upon both (i human monocyte derived macrophages (MDM monocultures, and (ii a sophisticated in vitro model of the human epithelial airway barrier. Both in vitro systems were exposed to MWCNTs either pre-coated with a porcine pulmonary surfactant (Curosurf or not. The effect of MWCNTs surface charge was also investigated in terms of amino (−NH2 and carboxyl (−COOH surface modifications. Results Pre-coating of MWCNTs with Curosurf affects their oxidative potential by increasing the reactive oxygen species levels and decreasing intracellular glutathione depletion in MDM as well as decreases the release of Tumour necrosis factor alpha (TNF-α. In addition, an induction of apoptosis was observed after exposure to Curosurf pre-coated MWCNTs. In triple cell-co cultures the release of Interleukin-8 (IL-8 was increased after exposure to Curosurf pre-coated MWCNTs. Effects of the MWCNTs functionalizations were minor in both MDM and triple cell co-cultures. Conclusions The present study clearly indicates that the pre-coating of MWCNTs with pulmonary surfactant more than the functionalization of the tubes is a key factor in determining their ability to cause oxidative stress, cytokine/chemokine release and apoptosis. Thus the coating of nano-objects with pulmonary

  10. Role of surfactant protein-A (SP-A) in lung injury in response to acute ozone exposure of SP-A deficient mice

    International Nuclear Information System (INIS)

    Millions are exposed to ozone levels above recommended limits, impairing lung function, causing epithelial damage and inflammation, and predisposing some individuals to pneumonia, asthma, and other lung conditions. Surfactant protein-A (SP-A) plays a role in host defense, the regulation of inflammation, and repair of tissue damage. We tested the hypothesis that the lungs of SP-A(-/-) (KO) mice are more susceptible to ozone-induced damage. We compared the effects of ozone on KO and wild type (WT) mice on the C57BL/6 genetic background by exposing them to 2 parts/million of ozone for 3 or 6 h and sacrificing them 0, 4, and 24 h later. Lungs were subject to bronchoalveolar lavage (BAL) or used to measure endpoints of oxidative stress and inflammation. Despite more total protein in BAL of KO mice after a 3 h ozone exposure, WT mice had increased oxidation of protein and had oxidized SP-A dimers. In KO mice there was epithelial damage as assessed by increased LDH activity and there was increased phospholipid content. In WT mice there were more BAL PMNs and elevated macrophage inflammatory protein (MIP)-2 and monocyte chemoattractant protein (MCP)-1. Changes in MIP-2 and MCP-1 were observed in both KO and WT, however mRNA levels differed. In KO mice MIP-2 mRNA levels changed little with ozone, but in WT levels they were significantly increased. In summary, several aspects of the inflammatory response differ between WT and KO mice. These in vivo findings appear to implicate SP-A in regulating inflammation and limiting epithelial damage in response to ozone exposure

  11. INHIBITION OF PROTEIN TYROSINE PHOSPHATASE ACTIVITY MEDIATES EPIDERMAL GROWTH FACTOR RECEPTOR SIGNALING IN HUMAN AIRWAY EPITHELIAL CELLS

    Science.gov (United States)

    Epidemiological studies have implicated zinc in the toxicity of ambient particulate matter (PM) inhalation. We previously showed that exposure to metal-laden PM inhibits protein tyrosine phosphatase (PTP) activity in human primary bronchial epithelial cells (HAEC) and leads t...

  12. Theophylline Represses IL-8 Secretion from Airway Smooth Muscle Cells Independently of Phosphodiesterase Inhibition. Novel Role as a Protein Phosphatase 2A Activator.

    Science.gov (United States)

    Patel, Brijeshkumar S; Rahman, Md Mostafizur; Rumzhum, Nowshin N; Oliver, Brian G; Verrills, Nicole M; Ammit, Alaina J

    2016-06-01

    Theophylline is an old drug experiencing a renaissance owing to its beneficial antiinflammatory effects in chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Multiple modes of antiinflammatory action have been reported, including inhibition of the enzymes that degrade cAMP-phosphodiesterase (PDE). Using primary cultures of airway smooth muscle (ASM) cells, we recently revealed that PDE4 inhibitors can potentiate the antiinflammatory action of β2-agonists by augmenting cAMP-dependent expression of the phosphatase that deactivates mitogen-activated protein kinase (MAPK)-MAPK phosphatase (MKP)-1. Therefore, the aim of this study was to address whether theophylline repressed cytokine production in a similar, PDE-dependent, MKP-1-mediated manner. Notably, theophylline did not potentiate cAMP release from ASM cells treated with the long-acting β2-agonist formoterol. Moreover, theophylline (0.1-10 μM) did not increase formoterol-induced MKP-1 messenger RNA expression nor protein up-regulation, consistent with the lack of cAMP generation. However, theophylline (at 10 μM) was antiinflammatory and repressed secretion of the neutrophil chemoattractant cytokine IL-8, which is produced in response to TNF-α. Because theophylline's effects were independent of PDE4 inhibition or antiinflammatory MKP-1, we then wished to elucidate the novel mechanisms responsible. We investigated the impact of theophylline on protein phosphatase (PP) 2A, a master controller of multiple inflammatory signaling pathways, and show that theophylline increases TNF-α-induced PP2A activity in ASM cells. Confirmatory results were obtained in A549 lung epithelial cells. PP2A activators have beneficial effects in ex vivo and in vivo models of respiratory disease. Thus, our study is the first to link theophylline with PP2A activation as a novel mechanism to control respiratory inflammation. PMID:26574643

  13. Clinical assessment and C-reactive protein (CRP), haptoglobin (Hp), and cardiac troponin I (cTnI) values of brachycephalic dogs with upper airway obstruction before and after surgery

    OpenAIRE

    Planellas, Marta; Cuenca, Rafaela; Tabar, Maria-Dolores; Bertolani, Coralie; Poncet, Cyrill; Closa, Josep M; Lorente, Juan; Cerón, José J.; Pastor, Josep

    2015-01-01

    Brachycephalic dogs have unique upper respiratory anatomy with abnormal breathing patterns that are similar to those in humans with obstructive sleep apnea syndrome (OSAS). The objectives of this multicenter prospective study were to assess the effects of surgical correction on clinical signs in dogs with brachycephalic airway obstructive syndrome (BAOS) and to evaluate the levels of several biomarkers [C-reactive protein (CRP); haptoglobin (Hp), and cardiac troponin I (cTnI)] used to determi...

  14. Leukocyte trafficking in alveoli and airway passages

    Directory of Open Access Journals (Sweden)

    Doerschuk Claire M

    2000-10-01

    Full Text Available Abstract Many pulmonary diseases preferentially affect the large airways or the alveoli. Although the mechanisms are often particular to each disease process, site-specific differences in leukocyte trafficking and the regulation of inflammation also occur. Differences in the process of margination, sequestration, adhesion, and migration occur that can be attributed to differences in anatomy, hemodynamics, and the expression of proteins. The large airways are nourished by the bronchial circulation, whereas the pulmonary circulation feeds the distal lung parenchyma. The presence of different cell types in large airways from those in alveoli might contribute to site-specific differences in the molecular regulation of the inflammatory process.

  15. Angiotensin I-Converting Enzyme inhibitory and antioxidant activities and surfactant properties of protein hydrolysates as obtained of Amaranthus hypochondriacus L. grain.

    Science.gov (United States)

    Soriano-Santos, J; Escalona-Buendía, H

    2015-04-01

    Even though some research has been carried out on surfactant properties of amaranth protein hydrolysates, their bio-functionality has not been studied yet. In this work amaranth grain Alb 1 and Glob were hydrolyzed (Alb 1H, Glob H) and foams and emulsions at optimal conditions (t, E/S, pH5) were prepared in order to assess techno-functional properties such as foaming (F) and emulsifying (E) (capacity (C) and stability (S)). FC and EC were much better for Glob H than for Alb H. Angiotensin I-converting enzyme-inhibitory activity was higher for Alb 1H (roughly 50 %) than that of Glob H (roughly 30 %). Scavenging of radicals activity (DPPH· or ABTS· (+) ) of Alb 1H and Glob H, at 2 mg/mL, was similar (approx. 40 %), but lower than Alb 1 (approx. 70 %), which was the best antioxidant. The low reducing power showed that hydrolysates barely donate an electron or hydrogen. Chelating activity on Cu(2+) was lower than that exhibited by Fe(2+,) which was remarkable, approx. 80 % as long as DH% > 10 %, where hydrolysates displayed high solubility (Alb 1H = 85 %, Glob H = 70 %) because of occurrence of 1-10 kDa peptides. Amaranth foams and emulsions prepared with protein hydrolysates have a potential as a nutraceutical food. PMID:25829587

  16. Leukocyte trafficking in alveoli and airway passages

    OpenAIRE

    Doerschuk Claire M

    2000-01-01

    Abstract Many pulmonary diseases preferentially affect the large airways or the alveoli. Although the mechanisms are often particular to each disease process, site-specific differences in leukocyte trafficking and the regulation of inflammation also occur. Differences in the process of margination, sequestration, adhesion, and migration occur that can be attributed to differences in anatomy, hemodynamics, and the expression of proteins. The large airways are nourished by the bronchial circula...

  17. 3D Model of Surfactant Replacement Therapy

    Science.gov (United States)

    Grotberg, James; Tai, Cheng-Feng; Filoche, Marcel

    2015-11-01

    Surfactant Replacement Therapy (SRT) involves instillation of a liquid-surfactant mixture directly into the lung airway tree. Though successful in neonatal applications, its use in adults had early success followed by failure. We present the first mathematical model of 3D SRT where a liquid plug propagates through the tree from forced inspiration. In two separate modeling steps, the plug first deposits a coating film on the airway wall which subtracts from its volume, a ``coating cost''. Then the plug splits unevenly at the airway bifurcation due to gravity. The steps are repeated until a plug ruptures or reaches the tree endpoint alveoli/acinus. The model generates 3D images of the resulting acinar distribution and calculates two global indexes, efficiency and homogeneity. Simulating published literature, the earlier successful adult SRT studies show comparatively good index values, while the later failed studies do not. Those unsuccessful studies used smaller dose volumes with higher concentration mixtures, apparently assuming a well mixed compartment. The model shows that adult lungs are not well mixed in SRT due to the coating cost and gravity effects. Returning to the higher dose volume protocols could save many thousands of lives annually in the US. Supported by NIH Grants HL85156, HL84370 and Agence Nationale de la Recherche, ANR no. 2010-BLAN-1119-05.

  18. The Physiologically Difficult Airway

    Directory of Open Access Journals (Sweden)

    Jarrod M. Mosier

    2015-12-01

    Full Text Available Airway management in critically ill patients involves the identification and management of the potentially difficult airway in order to avoid untoward complications. This focus on difficult airway management has traditionally referred to identifying anatomic characteristics of the patient that make either visualizing the glottic opening or placement of the tracheal tube through the vocal cords difficult. This paper will describe the physiologically difficult airway, in which physiologic derangements of the patient increase the risk of cardiovascular collapse from airway management. The four physiologically difficult airways described include hypoxemia, hypotension, severe metabolic acidosis, and right ventricular failure. The emergency physician should account for these physiologic derangements with airway management in critically ill patients regardless of the predicted anatomic difficulty of the intubation.

  19. Thermally cleavable surfactants

    Science.gov (United States)

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

    2006-04-04

    Two new surfactant molecules are reported which contain thermally labile Diels-Alder adducts connecting the polar and non-polar sections of each molecule. The two surfactants possess identical non-polar dodecyl tail segments but exhibit different polar headgroups. The surfactants become soluble in water when anionic salts are formed through the deprotonation of the surfactant headgroups by the addition of potassium hydroxide. When either surfactant is exposed to temperature above about 60.degree. C., the retro Diels-Alder reaction occurs, yielding hydrophilic and hydrophobic fragments and the aqueous solutions of the surfactants subsequently exhibit loss of all surface-active behavior.

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

    OpenAIRE

    Emily F A van 't Wout; Annemarie van Schadewijk; Ria van Boxtel; Dalton, Lucy E.; Clarke, Hanna J.; Jan Tommassen; Marciniak, Stefan J; Hiemstra, Pieter S.

    2015-01-01

    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 pr...

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

    OpenAIRE

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

    2005-01-01

    Control of surface chemistry and protein adsorption is important for using microfluidic devices for biochemical analysis and high-throughput screening assays. This paper describes the control of protein adsorption at the liquid-liquid interface in a plug-based microfluidic system. The microfluidic system uses multiphase flows of immiscible fluorous and aqueous fluids to form plugs, which are aqueous droplets that are completely surrounded by fluorocarbon oil and do not come into direct contac...

  2. Vacuolar ATPase Regulates Surfactant Secretion in Rat Alveolar Type II Cells by Modulating Lamellar Body Calcium

    OpenAIRE

    Chintagari, Narendranath Reddy; Mishra, Amarjit; Su, Lijing; Wang, Yang; Ayalew, Sahlu; Hartson, Steven D; Liu, Lin

    2010-01-01

    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 alveol...

  3. Structure and potential C-terminal dimerization of a recombinant mutant of surfactant-associated protein C in chloroform/methanol.

    Science.gov (United States)

    Luy, Burkhard; Diener, Alexander; Hummel, Rolf-Peter; Sturm, Ernst; Ulrich, Wolf-Rüdiger; Griesinger, Christian

    2004-06-01

    The solution structure of a recombinant mutant [rSP-C (FFI)] of the human surfactant-associated protein C (hSP-C) in a mixture of chloroform and methanol was determined by high-resolution NMR spectroscopy. rSP-C (FFI) contains a helix from Phe5 to the C-terminal Leu34 and is thus longer by two residues than the helix of porcine SP-C (pSP-C), which is reported to start at Val7 in the same solvent. Two sets of resonances at the C-terminus of the peptide were observed, which are explained by low-order oligomerization, probably dimerization of rSP-C (FFI) in its alpha-helical form. The dimerization may be induced by hydrogen bonding of the C-terminal carboxylic groups or by the strictly conserved C-terminal heptapeptide segment with a motif similar to the GxxxG dimerization motif of glycophorin A. Dimerization at the heptapeptide segment would be consistent with findings based on electrospray ionization MS data, chemical cross-linking studies, and CNBr cleavage data. PMID:15153097

  4. Absorption of PCB126 by upper airways impairs G protein-coupled receptor-mediated immune response

    Science.gov (United States)

    Shimada, Ana Lúcia B.; Cruz, Wesley S.; Loiola, Rodrigo A.; Drewes, Carine C.; Dörr, Fabiane; Figueiredo, Natália G.; Pinto, Ernani; Farsky, Sandra H. P.

    2015-10-01

    PCB126 is a dioxin-like polychlorinated biphenyl (PCB) environmental pollutant with a significant impact on human health, as it bioaccumulates and causes severe toxicity. PCB126-induced immune toxicity has been described, although the mechanisms have not been fully elucidated. In this study, an in vivo protocol of PCB126 intoxication into male Wistar rats by intranasal route was used, which has not yet been described. The intoxication was characterised by PCB126 accumulation in the lungs and liver, and enhanced aryl hydrocarbon receptor expression in the liver, lungs, kidneys, and adipose tissues. Moreover, an innate immune deficiency was characterised by impairment of adhesion receptors on blood leukocytes and by reduced blood neutrophil locomotion and oxidative burst activation elicited by ex vivo G protein-coupled receptor (GPCR) activation. Specificity of PCB126 actions on the GPCR pathway was shown by normal burst oxidative activation evoked by Toll-like receptor 4 and protein kinase C direct activation. Moreover, in vivo PCB180 intoxication did not alter adhesion receptors on blood leukocytes either blood neutrophil locomotion, and only partially reduced the GPCR-induced burst oxidative activation on neutrophils. Therefore, a novel mechanism of in vivo PCB126 toxicity is described which impairs a pivotal inflammatory pathway to the host defence against infections.

  5. Central airways remodeling in COPD patients

    Directory of Open Access Journals (Sweden)

    Pini L

    2014-09-01

    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

  6. Serum Levels of Vascular Endothelial Growth Factor and Insulin-like Growth Factor Binding Protein-3 in Obstructive Sleep Apnea Patients: Effect of Continuous Positive Airway Pressure Treatment

    Science.gov (United States)

    Archontogeorgis, Kostas; Nena, Evangelia; Papanas, Nikolaos; Xanthoudaki, Maria; Hatzizisi, Olga; Kyriazis, Georgios; Tsara, Venetia; Maltezos, Efstratios; Froudarakis, Marios; Steiropoulos, Paschalis

    2015-01-01

    Background and Aim: Hypoxia, a major feature of obstructive sleep apnea (OSA), modifies Vascular Endothelial Growth Factor (VEGF) and Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) levels, which contribute to atherogenesis and occurrence of cardiovascular (CV) events. We assessed and compared serum levels of VEGF and IGFBP-3 in newly diagnosed OSA patients and controls, to explore associations with anthropometric and sleep parameters and to study the effect of continuous positive airway pressure (CPAP) treatment on these levels. Materials and Methods: Serum levels of VEGF and IGFBP-3 were measured in 65 OSA patients and 31 age- and body mass index- matched controls. In OSA patients, measurements were repeated after 6 months of CPAP therapy. All participants were non-smokers, without any comorbidities or systemic medication use. Results: At baseline, serum VEGF levels in OSA patients were higher compared with controls (p<0.001), while IGFBP-3 levels were lower (1.41±0.56 vs. 1.61±0.38 μg/ml, p=0.039). VEGF levels correlated with apnea-hypopnea index (r=0.336, p=0.001) and oxygen desaturation index (r=0.282, p=0.007). After 6 months on CPAP treatment, VEGF levels decreased in OSA patients (p<0.001), while IGFBP-3 levels increased (p<0.001). Conclusion: In newly diagnosed OSA patients, serum levels of VEGF are elevated, while IGFBP-3 levels are low. After 6 months of CPAP treatment these levels change. These results may reflect an increased CV risk in untreated OSA patients, which is ameliorated after CPAP therapy. PMID:27006717

  7. Engineering Airway Epithelium

    Directory of Open Access Journals (Sweden)

    John P. Soleas

    2012-01-01

    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.

  8. Engineering Airway Epithelium

    OpenAIRE

    John P. Soleas; Paz, Ana; Marcus, Paula; McGuigan, Alison; Waddell, Thomas K.

    2012-01-01

    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 fun...

  9. Conquering the difficult airway.

    Science.gov (United States)

    Gandy, William E

    2008-01-01

    Every medic should practice regularly for the inevitable difficult airway case. Practice should include review of the causes of difficult airways, as well as skill practice. Having a preassembled airway kit can make your response to an unexpected difficult situation easier. Of all the devices mentioned, the bougie is the airway practitioner's best friend. Using the BURP technique, if not contraindicated, together with the bougie will enable you to intubate many difficult patients with confidence. Remember, "If your patient cannot breathe, nothing else matters. PMID:18251307

  10. Genetic Complexity of the Human Innate Host Defense Molecules, Surfactant Protein A1 (SP-A1) and SP-A2—Impact on Function

    OpenAIRE

    Floros, Joanna; Wang, Guirong; Mikerov, Anatoly N.

    2009-01-01

    Innate immunity mechanisms play a critical role in the primary response to invading pathogenic microorganisms and other insulting agents. The innate lung immune system includes lung surfactant, a lipoprotein complex that carries out a function essential for life, that is, reduction of the surface tension at the air–liquid interphase of the alveolar space. By means of this function, pulmonary surfactant prevents lung collapse, therefore ensuring normal lung function and lung health. Pulmonary ...

  11. CX3CR1 Is Expressed in Differentiated Human Ciliated Airway Cells and Co-Localizes with Respiratory Syncytial Virus on Cilia in a G Protein-Dependent Manner.

    Directory of Open Access Journals (Sweden)

    Kwang-Il Jeong

    Full Text Available Respiratory syncytial virus (RSV is the principal cause of bronchiolitis in infants and a significant healthcare problem. The RSV Glycoprotein (G mediates attachment of the virus to the cell membrane, which facilitates interaction of the RSV Fusion (F protein with nucleolin, thereby triggering fusion of the viral and cellular membranes. However, a host protein ligand for G has not yet been identified. Here we show that CX3CR1 is expressed in the motile cilia of differentiated human airway epithelial (HAE cells, and that CX3CR1 co-localizes with RSV particles. Upon infection, the distribution of CX3CR1 in these cells is significantly altered. Complete or partial deletion of RSV G results in viruses binding at least 72-fold less efficiently to cells, and reduces virus replication. Moreover, an antibody targeting an epitope near the G protein's CX3CR1-binding motif significantly inhibits binding of the virus to airway cells. Given previously published evidence of the interaction of G with CX3CR1 in human lymphocytes, these findings suggest a role for G in the interaction of RSV with ciliated lung cells. This interpretation is consistent with past studies showing a protective benefit in immunizing against G in animal models of RSV infection, and would support targeting the CX3CR1-G protein interaction for prophylaxis or therapy. CX3CR1 expression in lung epithelial cells may also have implications for other respiratory diseases such as asthma.

  12. Monoclonal antibody-assisted structure-function analysis of the carbohydrate recognition domain of surfactant protein D

    DEFF Research Database (Denmark)

    Hartshorn, Kevan L; White, Mitchell R; Rynkiewicz, Michael;

    2010-01-01

    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......335A), which 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 m...

  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.; van Eijk, Martin; Hartshorn, Max; Pemberton, Lily; Holmskov, Uffe; Crouch, Erika

    2006-01-01

    salivary gp-340 are identical in protein sequence, salivary gp-340 from one donor had significantly greater antiviral activity against avian-like IAV strains which preferentially bind sialic acids in alpha(2,3) linkage. A greater density of alpha(2,3)-linked sialic acids was present on the salivary gp-340...... 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...

  14. An overview of pulmonary surfactant in the neonate: genetics, metabolism, and the role of surfactant in health and disease.

    Science.gov (United States)

    Nkadi, Paul O; Merritt, T Allen; Pillers, De-Ann M

    2009-06-01

    Pulmonary surfactant is a complex mixture of phospholipids (PL) and proteins (SP) that reduce surface tension at the air-liquid interface of the alveolus. It is made up of about 70-80% PL, mainly dipalmitoylphosphatidylcholine (DPPC), 10% SP-A, B, C and D, and 10% neutral lipids, mainly cholesterol. Surfactant is synthesized, assembled, transported and secreted into the alveolus where it is degraded and then recycled. Metabolism of surfactant is slower in newborns, especially preterm, than in adults. Defective pulmonary surfactant metabolism results in respiratory distress with attendant morbidity and mortality. This occurs due to accelerated breakdown by oxidation, proteolytic degradation, inhibition or inherited defects of surfactant metabolism. Prenatal corticosteroids, surfactant replacement, whole lung lavage and lung transplantation have yielded results in managing some of these defects. Gene therapy could prove valuable in treating inherited defects of surfactant metabolism. PMID:19299177

  15. Hu.4-1BB-Fc fusion protein inhibits allergic inflammation and airway hyperresponsiveness in a murine model of asthma

    Directory of Open Access Journals (Sweden)

    Byoung-Ju Kim

    2011-09-01

    Full Text Available Purpose : 4-1BB (CD 137 is a costimulatory molecule expressed on activated T-cells. Repression by 4-1BB is thought to attenuate Th2-mediated allergic reactions. The aim of this study was to investigate the effect of 4-1BB on allergic airway inflammation in a murine asthma model. Methods : BALB/c mice were sensitized to and challenged with ovalbumin (OVA. Hu.4-1BB-Fc was administered 1 day before the first OVA sensitization or 1 day after the second OVA sensitization. Following antigen challenge, airway responsiveness to methacholine was assessed and bronchoalveolar lavage (BAL fluid was analyzed. Total immunoglobulin (Ig E, OVA-specific IgE, IgG1, and IgG2a levels in sera were measured by enzyme-linked immunosorbent assay. Lung pathology was also evaluated. Results : In mice treated with Hu.4-1BB-Fc before the first OVA sensitization, there was a marked decrease in airway hyperresponsiveness, total cell count, and eosinophil count in the BAL fluid. In addition, Hu.4-1BB-Fc treatment decreased serum OVA-specific IgG1 levels and increased serum IgG2a level significantly compared with the corresponding levels in mice sensitized to and challenged with OVA. Hu.4-1BB-Fc-treated mice also showed suppressed peribronchial and perivascular inflammatory cell infiltration. In contrast, treatment with Hu.4-1BB-Fc 1 day after sensitization had no effect on airway hyperresponsiveness and showed less suppression of inflammation in lung tissue. Conclusion : Administration of Hu.4-1BB-Fc can attenuate airway inflammation and hyperreactivity in a mouse model of allergic airway inflammation. In addition, administration before sensitization may be more effective. These findings suggest that 4-1BB may be a useful therapeutic molecule against asthma.

  16. Surfactant Treatment Threshold during NCPAP for the Treatment of Preterm Infants with Respiratory Distress Syndrome.

    Science.gov (United States)

    Dani, Carlo

    2016-08-01

    Although surfactant is the most studied drug in the preterm infant, the best criteria for treatment of preterm infants with respiratory distress syndrome (RDS) with surfactant have been not extensively investigated. We assessed the criteria used for deciding the rescue surfactant treatment of preterm infants with RDS in combination with nasal continuous positive airway pressure as reported by the main recent randomized controlled trials. We evaluated 10 studies and found that the criteria chosen for administering selective surfactant were very heterogeneous, different types and doses of surfactant were used, and this limits their applicability in the clinical practice. In conclusion, although current data seem to suggest that low threshold is better than high threshold, additional studies are necessary to identify the most effective criteria for selective surfactant treatment of preterm infants with RDS. PMID:27120482

  17. Human surfactant protein D alters oxidative stress and HMGA1 expression to induce p53 apoptotic pathway in eosinophil leukemic cell line.

    Directory of Open Access Journals (Sweden)

    Lakshna Mahajan

    Full Text Available Surfactant protein D (SP-D, an innate immune molecule, has an indispensable role in host defense and regulation of inflammation. Immune related functions regulated by SP-D include agglutination of pathogens, phagocytosis, oxidative burst, antigen presentation, T lymphocyte proliferation, cytokine secretion, induction of apoptosis and clearance of apoptotic cells. The present study unravels a novel ability of SP-D to reduce the viability of leukemic cells (eosinophilic leukemic cell line, AML14.3D10; acute myeloid leukemia cell line, THP-1; acute lymphoid leukemia cell lines, Jurkat, Raji; and human breast epithelial cell line, MCF-7, and explains the underlying mechanisms. SP-D and a recombinant fragment of human SP-D (rhSP-D induced G2/M phase cell cycle arrest, and dose and time-dependent apoptosis in the AML14.3D10 eosinophilic leukemia cell line. Levels of various apoptotic markers viz. activated p53, cleaved caspase-9 and PARP, along with G2/M checkpoints (p21 and Tyr15 phosphorylation of cdc2 showed significant increase in these cells. We further attempted to elucidate the underlying mechanisms of rhSP-D induced apoptosis using proteomic analysis. This approach identified large scale molecular changes initiated by SP-D in a human cell for the first time. Among others, the proteomics analysis highlighted a decreased expression of survival related proteins such as HMGA1, overexpression of proteins to protect the cells from oxidative burst, while a drastic decrease in mitochondrial antioxidant defense system. rhSP-D mediated enhanced oxidative burst in AML14.3D10 cells was confirmed, while antioxidant, N-acetyl-L-cysteine, abrogated the rhSP-D induced apoptosis. The rhSP-D mediated reduced viability was specific to the cancer cell lines and viability of human PBMCs from healthy controls was not affected. The study suggests involvement of SP-D in host's immunosurveillance and therapeutic potential of rhSP-D in the eosinophilic leukemia and

  18. Interleukin-20 promotes airway remodeling in asthma.

    Science.gov (United States)

    Gong, Wenbin; Wang, Xin; Zhang, Yuguo; Hao, Junqing; Xing, Chunyan; Chu, Qi; Wang, Guicheng; Zhao, Jiping; Wang, Junfei; Dong, Qian; Liu, Tian; Zhang, Yuanyuan; Dong, Liang

    2014-12-01

    Previous studies have demonstrated that interleukin-20 (IL-20) is a pro-inflammatory cytokine, and it has been implicated in psoriasis, lupus nephritis, rheumatoid arthritis, atherosclerosis, and ulcerative colitis. Little is known about the effects of IL-20 in airway remodeling in asthma. The aim of our study was to demonstrate the function of IL-20 in airway remodeling in asthma. To identify the expression of IL-20 and its receptor, IL-20R1/IL-20R2, in the airway epithelium in bronchial tissues, bronchial biopsy specimens were collected from patients and mice with asthma and healthy subjects and stained with specific antibodies. To characterize the effects of IL-20 in asthmatic airway remodeling, we silenced and stimulated IL-20 in cell lines isolated from mice by shRNA and recombinant protein approaches, respectively, and detected the expression of α-SMA and FN-1 by Western blot analysis. First, overexpression of IL-20 and its receptor, IL-20R1/IL-20R2, was detected in the airway epithelium collected from patients and mice with asthma. Second, IL-20 increased the expression of fibronectin-1 and α-SMA, and silencing of IL-20 in mouse lung epithelial (MLE)-12 cells decreased the expression of fibronectin-1 and α-SMA. IL-20 may be a critical cytokine in airway remodeling in asthma. This study indicates that targeting IL-20 and/or its receptors may be a new therapeutic strategy for asthma. PMID:25028099

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

    OpenAIRE

    Han, SeungHye; Mallampalli, Rama K.

    2015-01-01

    Pulmonary surfactant is essential for life as it lines the alveoli to lower surface tension, thereby preventing atelectasis during breathing. Surfactant is enriched with a relatively unique phospholipid, termed dipalmitoylphosphatidylcholine, and four surfactant-associated proteins, SP-A, SP-B, SP-C, and SP-D. The hydrophobic proteins, SP-B and SP-C, together with dipalmitoylphosphatidylcholine, confer surface tension–lowering properties to the material. The more hydrophilic surfactant compon...

  20. Surfactant alterations and treatment of lung transplant ischemia-reperfusion injury

    OpenAIRE

    Kaaij, Niels; Lachmann, Robert; Bogers, Ad; Lachmann, Burkhard

    2006-01-01

    textabstractThis review addresses surfactant alterations and treatment in lung transplant ischemia-reperfusion injury. Lung ischemia-reperfusion injury damages the endogenous surfactant system as a result of the production of reactive oxygen species, proteolytic enzymes and (phospho)lipases. Surfactant is composed of phospholipids and proteins and its main function is to reduce the surface tension inside the alveolus. Impairment of surfactant will cause atelectasis, influx of serum proteins, ...

  1. Airway distensibility in Chronic Obstructive Airway Disease

    DEFF Research Database (Denmark)

    Winkler Wille, Mathilde Marie; Pedersen, Jesper Holst; Dirksen, Asger; Petersen, Jens; De Bruijne, Marleen

    2013-01-01

    airway distensibility, defined as the ratio of relative change in lumen diameter to the relative change in total lung volume (TLV) divided by predicted total lung capacity (pTLC) . Methods – We included 1900 participants from the Danish Lung Cancer Screening Trial (DLCST); all randomized to annual low......-dose CT for a period of 5 years (table 1). Images were reconstructed both with high contrast resolution (3 mm, kernel C) for emphysema analysis and with high spatial resolution (1 mm, kernel D) for airway analysis. Images were analysed by in-house developed software designed to segment lungs and localize......), 10-20% (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...

  2. 早产儿支气管肺发育不良与肺表面活性物质蛋白基因多态性的相关研究%The Study on Relationship between Premature Bronchopulmonary Dysplasia and Gene Polymorphism of Surfactant Protein

    Institute of Scientific and Technical Information of China (English)

    谢云波

    2012-01-01

    With the increasing survival rate of preterm children,the problems of preterm children bronchopulmonary dysplasia( BPD ) are becoming prominent. The disease needs long-time oxygen and has high mortality. The survivals often have highly reactive airway disease,lower respiratory infection,feeding difficulties, and growth retardation,so it is one of the difficult problems in neonatal intensive care unit,which would be an important factor impacting on quality of life. Recent studies found that the incidence of BPD was significantly affected by complex interactions of genetic and environmental factors. Here is to make a review on the recent research of BPD and pulmonary surfactant protein gene polymorphism.%随着早产儿存活率的不断提高,早产儿支气管肺发育不良(BPD)的问题日益突出.BPD需长时间用氧治疗,病死率高,存活者常遗留高反应性呼吸道疾病、反复下呼吸道感染、喂养困难、生长发育迟缓等问题,因此一直是新生儿重症监护室最为棘手的问题之一,也是严重影响早产儿生存质量的重要因素.近年来研究认为BPD的发病明显受基因和环境因素相互作用的影响.现就近年来有关早产儿BPD与肺表面活性物质蛋白基因多态性的相关研究进行综述.

  3. Altered molecular specificity of surfactant phosphatidycholine synthesis in patients with acute respiratory distress syndrome

    OpenAIRE

    Dushianthan, Ahilanandan; Goss, Victoria; Cusack, Rebecca; Grocott, Michael P. W.; Postle, Anthony D

    2014-01-01

    Background Acute respiratory distress syndrome (ARDS) is a life-threatening critical illness, characterised by qualitative and quantitative surfactant compositional changes associated with premature airway collapse, gas-exchange abnormalities and acute hypoxic respiratory failure. The underlying mechanisms for this dysregulation in surfactant metabolisms are not fully explored. Lack of therapeutic benefits from clinical trials, highlight the importance of detailed in-vivo analysis and charact...

  4. Intubation-Surfactant: Extubation on Continuous Positive Pressure Ventilation. Who Are the Best Candidates?

    Directory of Open Access Journals (Sweden)

    Ognean Maria Livia

    2016-04-01

    Full Text Available Introduction: Respiratory distress syndrome (RDS continues to be the leading cause of illness and death in preterm infants. Studies indicate that INSURE strategy (INtubate-SURfactant administration and Extubate to nasal continuous positive airway pressure [nCPAP] is better than mechanical ventilation (MV with rescue surfactant, for the management of respiratory distress syndrome (RDS in very low birth weight (VLBW neonates, as it has a synergistic effect on alveolar stability.

  5. Effects of artificial surfactant on lung function and blood gases in idiopathic respiratory distress syndrome.

    OpenAIRE

    Milner, A D; Vyas, H.; Hopkin, I E

    1983-01-01

    We have investigated the effect of giving two 25 mg doses of dry surfactant powder to the airways of 10 preterm babies with severe idiopathic respiratory distress syndrome requiring intermittent positive pressure ventilation. No useful change in static total compliance or blood gases was seen. We conclude that dry surfactant powder does not have a role in the management of severe idiopathic respiratory distress syndrome.

  6. Intubation-Surfactant: Extubation on Continuous Positive Pressure Ventilation. Who Are the Best Candidates?

    OpenAIRE

    Ognean Maria Livia; Stoicescu Silvia-Maria; Boantă Oana; Năstase Leonard; Gliga Carmen; Cucerea Manuela

    2016-01-01

    Introduction: Respiratory distress syndrome (RDS) continues to be the leading cause of illness and death in preterm infants. Studies indicate that INSURE strategy (INtubate-SURfactant administration and Extubate to nasal continuous positive airway pressure [nCPAP]) is better than mechanical ventilation (MV) with rescue surfactant, for the management of respiratory distress syndrome (RDS) in very low birth weight (VLBW) neonates, as it has a synergistic effect on alveolar stability.

  7. Surfactant alteration and replacement in acute respiratory distress syndrome

    OpenAIRE

    Walmrath Dieter; Grimminger Friedrich; Markart Philipp; Schmidt Reinhold; Ruppert Clemens; Günther Andreas; Seeger Werner

    2001-01-01

    Abstract The acute respiratory distress syndrome (ARDS) is a frequent, life-threatening disease in which a marked increase in alveolar surface tension has been repeatedly observed. It is caused by factors including a lack of surface-active compounds, changes in the phospholipid, fatty acid, neutral lipid, and surfactant apoprotein composition, imbalance of the extracellular surfactant subtype distribution, inhibition of surfactant function by plasma protein leakage, incorporation of surfactan...

  8. Infasurf and Curosurf: Theoretical and Practical Considerations with New Surfactants

    OpenAIRE

    Nguyen, Thuy N.; Cunsolo, Stephanie M.; Gal, Peter; Ransom, J. Laurence

    2003-01-01

    Type II pneumocytes, normally responsible for surfactant production and release, are insufficiently formed and differentiated in the premature infant born before 34 weeks' gestation. Without an adequate amount of pulmonary surfactant, alveolar surface tension increases, leading to collapse and decreased lung compliance. Pulmonary surfactants are naturally occurring substances made of lipids and proteins. They lower surface tension at the interface between the air in the lungs, specifically at...

  9. Enhanced Surfactant Adsorption via Polymer Depletion Forces: A Simple Model for Reversing Surfactant Inhibition in Acute Respiratory Distress Syndrome

    OpenAIRE

    Stenger, Patrick C.; Zasadzinski, Joseph A.

    2006-01-01

    Lung surfactant adsorption to an air-water interface is strongly inhibited by an energy barrier imposed by the competitive adsorption of albumin and other surface-active serum proteins that are present in the lung during acute respiratory distress syndrome. This reduction in surfactant adsorption results in an increased surface tension in the lung and an increase in the work of breathing. The reduction in surfactant adsorption is quantitatively described using a variation of the classical Smo...

  10. An Overview of Pulmonary Surfactant in the Neonate: Genetics, Metabolism, and the Role of Surfactant in Health and Disease

    OpenAIRE

    Nkadi, Paul O.; Merritt, T. Allen; PILLERS, DE-ANN M.

    2009-01-01

    Pulmonary surfactant is a complex mixture of phospholipids (PL) and proteins (SP) that reduce surface tension at the air-liquid interface of the alveolus. It is made up of about 70% to 80% PL, mainly dipalmitoylphosphatidylcholine (DPPC), 10% SP-A, B, C and D, and 10% neutral lipids, mainly cholesterol. Surfactant is synthesized, assembled, transported and secreted into the alveolus where it is degraded and then recycled. Metabolism of surfactant is slower in newborns, especially preterm, tha...

  11. Tensiometric and Phase Domain Behavior of Lung Surfactant on Mucus-like Viscoelastic Hydrogels.

    Science.gov (United States)

    Schenck, Daniel M; Fiegel, Jennifer

    2016-03-01

    Lung surfactant has been observed at all surfaces of the airway lining fluids and is an important contributor to normal lung function. In the conducting airways, the surfactant film lies atop a viscoelastic mucus gel. In this work, we report on the characterization of the tensiometric and phase domain behavior of lung surfactant at the air-liquid interface of mucus-like viscoelastic gels. Poly(acrylic acid) hydrogels were formulated to serve as a model mucus with bulk rheological properties that matched those of tracheobronchial mucus secretions. Infasurf (Calfactant), a commercially available pulmonary surfactant derived from calf lung extract, was spread onto the hydrogel surface. The surface tension lowering ability and relaxation of Infasurf films on the hydrogels was quantified and compared to Infasurf behavior on an aqueous subphase. Infasurf phase domains during surface compression were characterized by fluorescence microscopy and phase shifting interferometry. We observed that increasing the bulk viscoelastic properties of the model mucus hydrogels reduced the ability of Infasurf films to lower surface tension and inhibited film relaxation. A shift in the formation of Infasurf condensed phase domains from smaller, more spherical domains to large, agglomerated, multilayer structures was observed with increasing viscoelastic properties of the subphase. These studies demonstrate that the surface behavior of lung surfactant on viscoelastic surfaces, such as those found in the conducting airways, differs significantly from aqueous, surfactant-laden systems. PMID:26894883

  12. Glucocorticoids and beta-adrenergic-receptor agonists: their combined effect on fetal rabbit lung surfactant.

    Science.gov (United States)

    Ekelund, L; Enhorning, G

    1985-08-15

    In a previous study on pregnant rabbits (Am J Obstet Gynecol 1983; 147:437) we found that a prolonged infusion of the beta 2-adrenergic-receptor agonist terbutaline would first cause a release of fetal pulmonary surfactant, so that more was available in the airways. However, the airway fluid then contained less surfactant, indicating a depletion of stores. Since terbutaline is often used in high doses as a tocolytic agent, surfactant depletion could be a serious side effect. With further studies on rabbits, we wanted to test the hypothesis that with an accelerated surfactant synthesis, achieved with glucocorticoids, the increased release, evoked with the terbutaline, would never cause a depletion of the surfactant stores. Our results supported this hypothesis. Betamethasone, administered to the pregnant doe on the twenty-sixth and twenty-seventh days of gestation, 0.1 mg/kg, increased compliance of the fetal lungs, and more phospholipid phosphorus could be lavaged from the airways. These effects were further increased when, following steroid administration, the doe was infused with terbutaline. Depletion of the surfactant stores was never seen when betamethasone was given prior to the beta-adrenergic-receptor agonist. PMID:3839627

  13. Gemini surfactants affect the structure, stability, and activity of ribonuclease Sa.

    Science.gov (United States)

    Amiri, Razieh; Bordbar, Abdol-Khalegh; Laurents, Douglas V

    2014-09-11

    Gemini surfactants have important advantages, e.g., low micromolar CMCs and slow millisecond monomer ↔ micelle kinetics, for membrane mimetics and for delivering nucleic acids for gene therapy or RNA silencing. However, as a prerequisite, it is important to characterize interactions occurring between Gemini surfactants and proteins. Here NMR and CD spectroscopies are employed to investigate the interactions of cationic Gemini surfactants with RNase Sa, a negatively charged ribonuclease. We find that RNase Sa binds Gemini surfactant monomers and micelles at pH values above 4 to form aggregates. Below pH 4, where the protein is positively charged, these aggregates dissolve and interactions are undetectable. Thermal denaturation experiments show that surfactant lowers RNase Sa's conformational stability, suggesting that surfactant binds the protein's denatured state preferentially. Finally, Gemini surfactants were found to bind RNA, leading to the formation of large complexes. Interestingly, Gemini surfactant binding did not prevent RNase Sa from cleaving RNA. PMID:25133582

  14. Surfactant protein group with molecular weights 28,000 to 36,000 daltons (SP 28-36) increases the association of phospholipids with freshly isolated type II cells

    International Nuclear Information System (INIS)

    Previous studies demonstrated that intratracheally-instilled radiolabelled subfractions of alveolar surfactant which contain SP 28-36 were incorporated into lamellar bodies to a greater extent than were SP 28-36-poor subfractions. The authors have characterized the effects of isolated SP 28-36 on the association of a mixture of surfactant-like synthetic lipids with isolated type II cells. Rat SP 28-36 was isolated according to modifications of the method of Hawgood et al., type II cells were isolated by differential adherence and averaged 84% pure. 267 nmol of lipid was incubated with 2.5 x 106 cells in 1ml of medium for 60 min. In the absence of added SP 28-36, the association of labelled dipalmitoylphosphatidylcholine (DPPC) averaged 0.67 (+/-.16) nmol DPPC/106 cells. SP 28-36 (15μg) increased the association of DPPC to 5.01 (+/- 0.94) nmol/106 cells (n=4). The association was dependent on protein concentration and reached a maximum at 10μg SP 28-36/ml. The effect was inhibited by the addition of polyclonal antibodies against SP 28-36. These results are consistent with a hypothesis that SP 28-36 mediates uptake of surfactant-like lipids by isolated type II cells

  15. Surfactant phospholipid metabolism

    OpenAIRE

    Agassandian, Marianna; Mallampalli, Rama K.

    2012-01-01

    Pulmonary surfactant is essential for life and is comprised of a complex lipoprotein-like mixture that lines the inner surface of the lung to prevent alveolar collapse at the end of expiration. The molecular composition of surfactant depends on highly integrated and regulated processes involving its biosynthesis, remodeling, degradation, and intracellular trafficking. Despite its multicomponent composition, the study of surfactant phospholipid metabolism has focused on two predominant compone...

  16. Surfactants in tribology

    CERN Document Server

    Biresaw, Girma

    2014-01-01

    Surface science and tribology play very critical roles in many industries. Manufacture and use of almost all consumer and industrial products rely on the application of advanced surface and tribological knowledge. The fourth in a series, Surfactants in Tribology, Volume 4 provides an update on research and development activities connecting surfactants and tribological phenomena. Written by renowned subject matter experts, the book demonstrates how improved design of surfactants can be harnessed to control tribological phenomena. Profusely illustrated and copiously referenced, the chapters also

  17. [The ocular surfactant system and its relevance in the dry eye].

    Science.gov (United States)

    Schicht, M; Posa, A; Paulsen, F; Bräuer, L

    2010-11-01

    The amphiphilic surfactant proteins B (SP-B) and C (SP-C) are tightly bound to phospholipids. These proteins play important roles in maintaining the surface tension-lowering properties of pulmonary surfactant. Surfactant protein A (SP-A) and D (SP-D) are hydrophilic and are thought to have a role in recycling surfactant and, especially, in improving host defense in the lung. Moreover, SP-A supports the hydrophobic surfactant proteins B and during surfactant subtype assembly and inhibits the secretion of lamellar bodies into the alveolar space. During recent years surfactant proteins have also been detected at locations outside the lung such as the lacrimal apparatus. In this review, the latest information regarding SP function and regulation in the human lacrimal system, the tear film and the ocular surface is summarised with regard to dry eye, rheological and antimicrobial properties of the tear film, tear outflow, certain disease states and possible therapeutic perspectives. PMID:21077020

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

    Directory of Open Access Journals (Sweden)

    Schaller Peter

    2006-03-01

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

  19. Surfactant Sector Needs Urgent Readjustment

    Institute of Scientific and Technical Information of China (English)

    Huang Hongzhou

    2007-01-01

    @@ Surfactant industrial system has been basically established After 50 years' development, China has already established a surfactant industrial system with a relatively complete product portfolio and can produce 4714 varieties of surfactants in cationic,anionic, nonionic and amphoteric categories.

  20. Nucleotide-mediated airway clearance.

    Science.gov (United States)

    Schmid, Andreas; Clunes, Lucy A; Salathe, Mathias; Verdugo, Pedro; Dietl, Paul; Davis, C William; Tarran, Robert

    2011-01-01

    A thin layer of airway surface liquid (ASL) lines the entire surface of the lung and is the first point of contact between the lung and the environment. Surfactants contained within this layer are secreted in the alveolar region and are required to maintain a low surface tension and to prevent alveolar collapse. Mucins are secreted into the ASL throughout the respiratory tract and serve to intercept inhaled pathogens, allergens and toxins. Their removal by mucociliary clearance (MCC) is facilitated by cilia beating and hydration of the ASL by active ion transport. Throughout the lung, secretion, ion transport and cilia beating are under purinergic control. Pulmonary epithelia release ATP into the ASL which acts in an autocrine fashion on P2Y(2) (ATP) receptors. The enzymatic network describes in Chap. 2 then mounts a secondary wave of signaling by surface conversion of ATP into adenosine (ADO), which induces A(2B) (ADO) receptor-mediated responses. This chapter offers a comprehensive description of MCC and the extensive ramifications of the purinergic signaling network on pulmonary surfaces. PMID:21560046

  1. The influence of surfactant on the propagation of a semi-infinite bubble through a liquid- filled compliant channel

    Science.gov (United States)

    Halpern, David; Gaver, Donald

    2011-11-01

    Pulmonary airway closure may occur as a result of fluid accumulation and surfactant insufficiency. This results in ``compliant collapse'' with the airway walls buckled and held in apposition by a liquid plug that blocks the passage of air. Airway reopening is vital to the recovery of adequate ventilation, but has been associated with ventilator- induced injury because of the exposure of airway epithelial cells to large pressure gradients. Surfactant replacement is helpful in modulating this harmful stimulus, but is limited in its effectiveness due to slow surfactant adsorption. We investigate the effect of surfactant on reopening by considering the steady two-dimensional motion of a semi-infinite bubble propagating through a liquid-filled compliant channel doped with soluble surfactant. Many parameters affect reopening, but we primarily investigate the capillary number Ca (the ratio of viscous to surface tension forces), the reopening (bubble) pressure pb, the adsorption depth parameter λ (a bulk concentration parameter) and the bulk Peclet number Peb (the ratio of bulk convection to diffusion). The behavior of this system, and the impact of the flow field on surfactant transport and the applied stresses on the wall will be discussed. Funded by NIH R01-HL81266.

  2. Use of therapeutic surfactant lavage in a preterm infant with massive pulmonary hemorrhage

    Directory of Open Access Journals (Sweden)

    Ino Kanavaki

    2012-08-01

    Full Text Available We report a case of a premature infant presenting with recurrent pulmonary hemorrhage in which we performed a therapeutic lavage with diluted surfactant after an acute episode of bleeding with severe intractable hypoxemia. Repeated small aliquots of diluted surfactant (10x2 mL allowed rapid improvement in oxygenation and reduction of required mean airway pressures during high frequency oscillatory ventilation. This observation may suggest that surfactant lavage could be beneficial in massive pulmonary hemorrhage in infants. A randomized controlled trial might be needed to clarify the potential benefit of this therapeutic intervention on outcome of infants suffering from this life-threatening complication.

  3. Blockage of upper airway

    Science.gov (United States)

    ... is made through the neck into the airway ( tracheostomy or cricothyrotomy). If the obstruction is due to ... team. Related MedlinePlus Health Topics Choking Throat Disorders Tracheal Disorders Browse the Encyclopedia A.D.A.M., Inc. ...

  4. Equine recurrent airway obstruction

    OpenAIRE

    Artur Niedźwiedź

    2014-01-01

    Equine Recurrent Airway Obstruction (RAO), also known as heaves or broken wind, is one of the most common disease in middle-aged horses. Inflammation of the airway is inducted by organic dust exposure. This disease is characterized by neutrophilic inflammation, bronchospasm, excessive mucus production and pathologic changes in the bronchiolar walls. Clinical signs are resolved in 3-4 weeks after environmental changes. Horses suffering from RAO are susceptible to allergens throughout their liv...

  5. Dynamic covalent surfactants

    NARCIS (Netherlands)

    Minkenberg, C.B.

    2012-01-01

    In this thesis the development of surfactant aggregates with fast exchange dynamics between the aggregated and non-aggregated state is described. Dynamic surfactant exchange plays an important role in natural systems, for instance in cell signaling, cell division, and uptake and release of cargo. Re

  6. Fundamentals of surfactant sputtering

    Energy Technology Data Exchange (ETDEWEB)

    Hofsaess, Hans [Second Institute of Physics, Georg-August University Goettingen, Friedrich-Hund-Platz 1, 37077 Goettingen (Germany)], E-mail: hans.hofsaess@phys.uni-goettingen.de; Zhang Kun [Second Institute of Physics, Georg-August University Goettingen, Friedrich-Hund-Platz 1, 37077 Goettingen (Germany)

    2009-08-15

    We introduce a new sputter technique, utilizing the steady-state coverage of a substrate surface with up to 10{sup 16} cm{sup -2} of foreign atoms simultaneously during sputter erosion by combined ion irradiation and atom deposition. These atoms strongly modify the substrate sputter yield on atomic to macroscopic length scales and therefore act as surfactant atoms (a blend of 'surface active agent'). Depending on the surfactant-substrate combination, the novel technique allows enhanced surface smoothing, generation of novel surface patterns, shaping of surfaces and formation of ultra-thin films. Sputter yield attenuation is demonstrated for sputtering of Si and Fe substrates and different surfactant species using 5 keV Xe ions at different incidence angles and fluences up to 10{sup 17} cm{sup -2}. Analytical approaches and Monte Carlo simulations are used to predict the sputtering yield attenuation as function of surfactant coverage. For sputtering of Si with Au surfactants we observe high sputter yields despite a steady-state surfactant coverage, which can be explained by strong ion-induced interdiffusion of substrate and surfactant atoms and the formation of a buried Au{sub x}Si surfactant layer in dynamic equilibrium.

  7. Fundamentals of surfactant sputtering

    International Nuclear Information System (INIS)

    We introduce a new sputter technique, utilizing the steady-state coverage of a substrate surface with up to 1016 cm-2 of foreign atoms simultaneously during sputter erosion by combined ion irradiation and atom deposition. These atoms strongly modify the substrate sputter yield on atomic to macroscopic length scales and therefore act as surfactant atoms (a blend of 'surface active agent'). Depending on the surfactant-substrate combination, the novel technique allows enhanced surface smoothing, generation of novel surface patterns, shaping of surfaces and formation of ultra-thin films. Sputter yield attenuation is demonstrated for sputtering of Si and Fe substrates and different surfactant species using 5 keV Xe ions at different incidence angles and fluences up to 1017 cm-2. Analytical approaches and Monte Carlo simulations are used to predict the sputtering yield attenuation as function of surfactant coverage. For sputtering of Si with Au surfactants we observe high sputter yields despite a steady-state surfactant coverage, which can be explained by strong ion-induced interdiffusion of substrate and surfactant atoms and the formation of a buried AuxSi surfactant layer in dynamic equilibrium.

  8. Advances in reactive surfactants.

    Science.gov (United States)

    Guyot, A

    2004-05-20

    The study of reactive surfactants and their applications in the synthesis of latexes for waterborne coatings has been recently boosted by two successive European programmes, involving all together eight academic and five industrial laboratories. The most significant results were obtained using surfactants derived from maleic and related anhydrides, or both nonionic and anionic reactive polymeric surfactants. Such surfactants are able to improve the stability of styrenic and acrylic latexes vs. various constraints, such as electrolyte addition, freeze-thawing tests or extraction with alcohol or acetone. The properties of films used in waterborne coatings are also improved in case of water exposure (less water uptake, dimensional stability), as well as improved weatherability, and blocking properties. Formulations for woodstain varnishes, metal coating of printing inks, based on the use of simple polymerizable surfactants, are now in the market. PMID:15072924

  9. Regulation of pulmonary surfactant apoprotein SP 28-36 gene in fetal human lung.

    OpenAIRE

    Ballard, P L; Hawgood, S; Liley, H; Wellenstein, G.; Gonzales, L W; Benson, B; Cordell, B.; White, R T

    1986-01-01

    Pulmonary surfactant stabilizes lung alveoli, preventing respiratory failure and hyaline membrane disease in premature infants. In addition to lipids, surfactant contains apoproteins that are thought to be critical for normal surfactant function. We have examined the ontogeny and regulation of the major surfactant-associated protein of molecular mass 28-36 kDa (SP 28-36) in human fetal lung. SP 28-36 was not detected in tissue from second trimester abortuses by either immunoblot analysis or e...

  10. Effect of Cholesterol on the Biophysical and Physiological Properties of a Clinical Pulmonary Surfactant

    OpenAIRE

    Keating, Eleonora; Rahman, Luna; Francis, James; Petersen, Anne; Possmayer, Fred; Veldhuizen, Ruud; Petersen, Nils O.

    2007-01-01

    Pulmonary surfactant is a complex mixture of lipids and proteins that forms a surface-active film at the air-water interface of alveoli capable of reducing surface tension to near 0 mN/m. The role of cholesterol, the major neutral lipid component of pulmonary surfactant, remains uncertain. We studied the physiological effect of cholesterol by monitoring blood oxygenation levels of surfactant-deficient rats treated or not treated with bovine lipid extract surfactant (BLES) containing zero or p...

  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

    2011-01-01

    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

    2012-01-01

    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. Nasal Continuous Positive Airway Pressure Combined with Pulmonary Surfactant for the Treatment of Premature Respiratory Distress Syndrome%经鼻持续气道正压通气联合肺泡表面活性物质治疗早产儿呼吸窘迫综合征

    Institute of Scientific and Technical Information of China (English)

    龙飞舞; 唐政华; 刘涛

    2011-01-01

    [目的]探讨经鼻持续气道正压通气(n-CPAP)联合肺泡表面活性物质(PS)治疗早产儿呼吸窘迫综合征(NRDS)的疗效.[方法]联合应用n-CPAP和PS治疗40例早产儿NRDS患儿,对治疗前后动脉血气分析情况、临床疗效、住院天数、胸部X线变化及相关并发症等进行观察.[结果]两组治疗后不同时间血气分析比较,联合治疗组较对照组明显改善(P<0.01);治愈率联合治疗组较对照组高(P<0.05);住院天数、CPAP时间及并发症发生率联合治疗组较对照组少(P<0.05);胸部X线片典型NRDS改变的改善率联合治疗组显著高于对照组(P<0.01).[结论]经鼻持续气道正压通气和PS能快速有效治疗早产儿NRDS,减少并发症的发生并改善患儿预后,值得临床推广应用.%[Objective]To explore the effect of nasal continuous positive airway pressure(n-CPAP) combined with pulmonary surfactant(PS) for the treatment of neonatal respiratory distress syndrome(NRDA) in premature infants. [Methods]Forty premature infants with NRDS were treated with n-CPAP combined with PS. Arterial blood-gas analysis status, clinical efficacy, hospitalized day, the change of X-ray chest film and related complications before and after treatment were observed. [Results] Compared with the control group,the blood-gas analysis status in combination therapy group at different time after treatment improved signifi cantly ( P <0.01). The recovery rate of combination therapy group was higher than that of the control group ( P <0.05). The hospital day, CPAP time and the incidence of complications of combination therapy group were significantly less than those of the control group( P <0.05). The improvement rate of the typical change of NRDS by X-ray chest film in combination therapy group was higher than that in the control group( P <0.01). [Conclusion]The n-CPAP combined with PS is effective and rapid way to treat the premature infants with NRDS. The n-CPAP combined with PS can

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    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......, neutrophil airway inflammation increases airway closure during bronchoconstriction, while eosinophil airway inflammation increases airway hyperresponsiveness (AHR). METHODS: Asthmatic subjects (n = 26), aged ≥55 years (68% female), were studied, and AHR to 4.5% saline challenge was measured by the response......-dose ratio (%fall in forced expiratory volume in 1 s (FEV1 )/mg saline). Airway closure was assessed during bronchoconstriction percent change in forced vital capacity (FVC)/percent change in FEV1 (i.e. Closing Index). Airway inflammation was assessed by induced sputum and exhaled nitric oxide (eNO). RESULTS...

  15. Role of upper airway ultrasound in airway management.

    Science.gov (United States)

    Osman, Adi; Sum, Kok Meng

    2016-01-01

    Upper airway ultrasound is a valuable, non-invasive, simple, and portable point of care ultrasound (POCUS) for evaluation of airway management even in anatomy distorted by pathology or trauma. Ultrasound enables us to identify important sonoanatomy of the upper airway such as thyroid cartilage, epiglottis, cricoid cartilage, cricothyroid membrane, tracheal cartilages, and esophagus. Understanding this applied sonoanatomy facilitates clinician to use ultrasound in assessment of airway anatomy for difficult intubation, ETT and LMA placement and depth, assessment of airway size, ultrasound-guided invasive procedures such as percutaneous needle cricothyroidotomy and tracheostomy, prediction of postextubation stridor and left double-lumen bronchial tube size, and detecting upper airway pathologies. Widespread POCUS awareness, better technological advancements, portability, and availability of ultrasound in most critical areas facilitate upper airway ultrasound to become the potential first-line non-invasive airway assessment tool in the future. PMID:27529028

  16. Upper airway radiographs in infants with upper airway insufficiency.

    OpenAIRE

    Tonkin, S L; Davis, S.L.; Gunn, T R

    1994-01-01

    Upper airway measurements in nine infants considered to be at risk of upper airway insufficiency, six of whom presented after an apnoeic episode, were compared with measurements taken in two age groups of healthy infants. Paired, inspiratory and expiratory, lateral upper airway radiographs were obtained while the infants were awake and breathing quietly. The radiographs of all nine infants demonstrated narrowing in the oropharyngeal portion of the airway during inspiration and in six infants ...

  17. Metathesis depolymerizable surfactants

    Science.gov (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.

    2008-04-15

    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.

  18. Surfactant alteration and replacement in acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Walmrath Dieter

    2001-10-01

    Full Text Available Abstract The acute respiratory distress syndrome (ARDS is a frequent, life-threatening disease in which a marked increase in alveolar surface tension has been repeatedly observed. It is caused by factors including a lack of surface-active compounds, changes in the phospholipid, fatty acid, neutral lipid, and surfactant apoprotein composition, imbalance of the extracellular surfactant subtype distribution, inhibition of surfactant function by plasma protein leakage, incorporation of surfactant phospholipids and apoproteins into polymerizing fibrin, and damage/inhibition of surfactant compounds by inflammatory mediators. There is now good evidence that these surfactant abnormalities promote alveolar instability and collapse and, consequently, loss of compliance and the profound gas exchange abnormalities seen in ARDS. An acute improvement of gas exchange properties together with a far-reaching restoration of surfactant properties was encountered in recently performed pilot studies. Here we summarize what is known about the kind and severity of surfactant changes occuring in ARDS, the contribution of these changes to lung failure, and the role of surfactant administration for therapy of ARDS.

  19. Dimeric N-terminal segment of human surfactant protein B (dSP-B(1-25)) has enhanced surface properties compared to monomeric SP-B(1-25).

    OpenAIRE

    Veldhuizen, E J; Waring, A J; Walther, F. J.; Batenburg, J.J.; van Golde, L M; Haagsman, H.P.

    2000-01-01

    Surfactant protein B (SP-B) is a 17-kDa dimeric protein produced by alveolar type II cells. Its main function is to lower the surface tension by inserting lipids into the air/liquid interface of the lung. SP-B's function can be mimicked by a 25-amino acid peptide, SP-B(1-25), which is based on the N-terminal sequence of SP-B. We synthesized a dimeric version of this peptide, dSP-B(1-25), and the two peptides were tested for their surface activity. Both SP-B(1-25) and dSP-B(1-25) showed good l...

  20. Three-dimensional model of surfactant replacement therapy.

    Science.gov (United States)

    Filoche, Marcel; Tai, Cheng-Feng; Grotberg, James B

    2015-07-28

    Surfactant replacement therapy (SRT) involves instillation of a liquid-surfactant mixture directly into the lung airway tree. It is widely successful for treating surfactant deficiency in premature neonates who develop neonatal respiratory distress syndrome (NRDS). However, when applied to adults with acute respiratory distress syndrome (ARDS), early successes were followed by failures. This unexpected and puzzling situation is a vexing issue in the pulmonary community. A pressing question is whether the instilled surfactant mixture actually reaches the adult alveoli/acinus in therapeutic amounts. In this study, to our knowledge, we present the first mathematical model of SRT in a 3D lung structure to provide insight into answering this and other questions. The delivery is computed from fluid mechanical principals for 3D models of the lung airway tree for neonates and adults. A liquid plug propagates through the tree from forced inspiration. In two separate modeling steps, the plug deposits a coating film on the airway wall and then splits unevenly at the bifurcation due to gravity. The model generates 3D images of the resulting acinar distribution and calculates two global indexes, efficiency and homogeneity. Simulating published procedural methods, we show the neonatal lung is a well-mixed compartment, whereas the adult lung is not. The earlier, successful adult SRT studies show comparatively good index values implying adequate delivery. The later, failed studies used different protocols resulting in very low values of both indexes, consistent with inadequate acinar delivery. Reasons for these differences and the evolution of failure from success are outlined and potential remedies discussed. PMID:26170310

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

    DEFF Research Database (Denmark)

    Bousquet, J; Addis, A; Adcock, I;

    2014-01-01

    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...

  2. Postnatal development of the bronchiolar club cells of distal airways in the mouse lung: stereological and molecular biological studies.

    Science.gov (United States)

    Karnati, Srikanth; Graulich, Tilman; Oruqaj, Gani; Pfreimer, Susanne; Seimetz, Michael; Stamme, Cordula; Mariani, Thomas J; Weissmann, Norbert; Mühlfeld, Christian; Baumgart-Vogt, Eveline

    2016-06-01

    Club (Clara) cells are nonciliated secretory epithelial cells present in bronchioles of distal pulmonary airways. So far, no information is available on the postnatal differentiation of club cells by a combination of molecular biological, biochemical, and stereological approaches in the murine lung. Therefore, the present study was designed to investigate the changes in the club cell secretory proteins (CC10, surfactant proteins A, B and D) and club cell abundance within the epithelium of bronchioles of distal airways during the postnatal development of the mouse lung. Perfusion-fixed murine lungs of three developmental stages (newborn, 15-day-old and adult) were used. Frozen, unfixed lungs were used for cryosectioning and subsequent laser-assisted microdissection of bronchiolar epithelial cells and RT-PCR analyses. High resolution analyses of the three-dimensional structures and composition of lung airways were obtained by scanning electron microscopy. Finally, using design-based stereology, the total and average club cell volume and the volume of secretory granules were quantified by light and transmission electron microscopy. Our results reveal that murine club cells are immature at birth and differentiate postnatally. Further, increase of the club cell volume and number of intracellular granules are closely correlated to the total lung volume enlargement. However, secretory granule density was only increased within the first 15 days of postnatal development. The differentiation is accompanied by a decrease in glycogen content, and a close positive relationship between CC10 expression and secretory granule abundance. Taken together, our data are consistent with the concept that the morphological and functional differentiation of club cells is a postnatal phenomenon. PMID:26796206

  3. New Surfactant with SP-B and C Analogs Gives Survival Benefit after Inactivation in Preterm Lambs

    OpenAIRE

    Matthias Seehase; Collins, Jennifer J. P.; Elke Kuypers; Reint K Jellema; Ophelders, Daan R. M. G.; Ospina, Olga L.; Perez-Gil, J; Federico Bianco; Raffaella Garzia; Roberta Razzetti; Boris W Kramer

    2012-01-01

    BACKGROUND: Respiratory distress syndrome in preterm babies is caused by a pulmonary surfactant deficiency, but also by its inactivation due to various conditions, including plasma protein leakage. Surfactant replacement therapy is well established, but clinical observations and in vitro experiments suggested that its efficacy may be impaired by inactivation. A new synthetic surfactant (CHF 5633), containing synthetic surfactant protein B and C analogs, has shown comparable effects on oxygena...

  4. Airway reconstruction in children

    Directory of Open Access Journals (Sweden)

    Rao Sanjay

    2009-01-01

    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.

  5. Surfactant phospholipid metabolism.

    Science.gov (United States)

    Agassandian, Marianna; Mallampalli, Rama K

    2013-03-01

    Pulmonary surfactant is essential for life and is composed of a complex lipoprotein-like mixture that lines the inner surface of the lung to prevent alveolar collapse at the end of expiration. The molecular composition of surfactant depends on highly integrated and regulated processes involving its biosynthesis, remodeling, degradation, and intracellular trafficking. Despite its multicomponent composition, the study of surfactant phospholipid metabolism has focused on two predominant components, disaturated phosphatidylcholine that confers surface-tension lowering activities, and phosphatidylglycerol, recently implicated in innate immune defense. Future studies providing a better understanding of the molecular control and physiological relevance of minor surfactant lipid components are needed. This article is part of a Special Issue entitled Phospholipids and Phospholipid Metabolism. PMID:23026158

  6. Phosphine oxide surfactants revisited.

    Science.gov (United States)

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

    2016-04-01

    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. PMID:26869216

  7. Other indications for surfactant].

    OpenAIRE

    PROENÇA FERNANDES, E.; Carvalho, C; Silva, A.; Ferreira, P.; Alegria, A.; Lopes, L.; AREIAS, M.A.

    2002-01-01

    An Esp Pediatr. 2002 Jan;56(1):45-8. [Other indications for surfactant] [Article in Spanish] Proença Fernandes E, Carvalho C, Silva A, Ferreira P, Alegria A, Lopes L, Areias MA. Unidades de Cuidados Intensivos Neonatales y Pediátricos, Hospital Maria Pia, Spain. Abstract OBJECTIVE: The introduction of surfactant replacement therapy in the management of respiratory distress syndrome in the premature infant was a remarkable advance in neonatal intensive care. In the last few y...

  8. Pharmacoeconomics of Surfactant Therapy

    OpenAIRE

    Barbarello-Andrews, Liza; Marsh, Wallace

    2006-01-01

    Surfactant therapy has become an integral part of the standard of care for treating premature infants with respiratory distress syndrome (RDS). Institutions that routinely treat this patient population have to select a surfactant based upon clinical and pharmacoeconomic considerations. Pharmacoeconomic studies have established the cost-effectiveness of individual agents based on a variety of factors, including length of hospitalization, mortality odds ratio, and other direct medical costs. Th...

  9. Non Invasive Surfactant Application

    OpenAIRE

    Hacer Yapicioglu; Eren Kale Cekinmez; Ferda Ozlu

    2013-01-01

    Surfactant replacement therapy has been the mainstay of treatment for preterm infants with respiratory distress syndrome for more than twenty years. In recent years, the growing interest in noninvasive ventilation has led to novel approaches of administration. Non-invasive techniques of respiratory support were developed in order to reduce the adverse effects associated with ventilation via an endotracheal tube. Noninvasive surfactant administration technique during spontaneous breathing alon...

  10. Comparison of INSURE method with conventional mechanical ventilation after surfactant administration in preterm infants with respiratory distress syndrome: therapeutic challenge.

    OpenAIRE

    Fatemeh Sadat Nayeri; Tahereh Esmaeilnia Shirvani; Majid Aminnezhad; Elaheh Amini; Hossein Dalili; Faezeh Moghimpour Bijani

    2014-01-01

    Administration of endotracheal surfactant is potentially the main treatment for neonates suffering from RDS (Respiratory Distress Syndrome), which is followed by mechanical ventilation. Late and severe complications may develop as a consequence of using mechanical ventilation. In this study, conventional methods for treatment of RDS are compared with surfactant administration, use of mechanical ventilation for a brief period and NCPAP (Nasal Continuous Positive Airway Pressure), (INSURE metho...

  11. Early administration of surfactant via a thin intratracheal catheter in preterm infants with respiratory distress syndrome: Feasibility and outcome

    OpenAIRE

    Mohammadizadeh, Majid; Ardestani, Azam Ghehsareh; Sadeghnia, Ali Reza

    2015-01-01

    Objective: Currently, the method of early nasal continuous positive airway pressure (nCPAP) and selective administration of surfactant via an endotracheal tube is widely used in the treatment of respiratory distress syndrome (RDS) in premature infants. To prevent complications related to endotracheal intubation and even a brief period of mechanical ventilation, in this study, we compared the effectiveness of surfactant administration via a thin intratracheal catheter versus the current method...

  12. The OPTIMIST-A trial: evaluation of minimally-invasive surfactant therapy in preterm infants 25–28 weeks gestation

    OpenAIRE

    Peter A. Dargaville; Kamlin, Camille Omar F; De Paoli, Antonio G; Carlin, John B.; Orsini, Francesca; Soll, Roger F; Davis, Peter G

    2014-01-01

    Background It is now recognized that preterm infants ≤28 weeks gestation can be effectively supported from the outset with nasal continuous positive airway pressure. However, this form of respiratory therapy may fail to adequately support those infants with significant surfactant deficiency, with the result that intubation and delayed surfactant therapy are then required. Infants following this path are known to have a higher risk of adverse outcomes, including death, bronchopulmonary dysplas...

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    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...... increases in pi did not occur when surfactants were applied to subphases containing serum. Components of serum are surface active and adsorb reversibly to the interface increasing pi up to a concentration-dependent saturation value, pi(max). When surfactants were applied to subphases containing serum, the...

  14. Equine recurrent airway obstruction

    Directory of Open Access Journals (Sweden)

    Artur Niedźwiedź

    2014-10-01

    Full Text Available Equine Recurrent Airway Obstruction (RAO, also known as heaves or broken wind, is one of the most common disease in middle-aged horses. Inflammation of the airway is inducted by organic dust exposure. This disease is characterized by neutrophilic inflammation, bronchospasm, excessive mucus production and pathologic changes in the bronchiolar walls. Clinical signs are resolved in 3-4 weeks after environmental changes. Horses suffering from RAO are susceptible to allergens throughout their lives, therefore they should be properly managed. In therapy the most importanthing is to eliminate dustexposure, administration of corticosteroids and use bronchodilators to improve pulmonary function.

  15. Airways microbiota: Hidden Trojan horses in asbestos exposed individuals?

    Science.gov (United States)

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

    2014-11-01

    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). PMID:25262213

  16. Issues of critical airway management (Which anesthesia; which surgical airway?

    Directory of Open Access Journals (Sweden)

    Fabrizio Giuseppe Bonanno

    2012-01-01

    Full Text Available Which anesthesia for patients with critical airway? Safe and effective analgesia and anesthesia in critical airway is a skilled task especially after severe maxillofacial injury combined with head injury and hemorrhagic shock. If on one side sedation is wanted, on the other hand it may worsen the airway and hemodynamic situation to a point where hypoventilation and decrease of blood pressure, common side-effect of many opioids, may prejudice the patient′s level of consciousness and hemodynamic compensation, compounding an already critical situation. What to do when endotracheal intubation fails and blood is trickling down the airways in an unconscious patient or when a conscious patient has to sit up to breathe? Which surgical airway in critical airway? Comparative studies among the various methods of emergency surgical airway would be unethical; furthermore, operator′s training and experience is relevant for indications and performance.

  17. Issues of critical airway management (Which anesthesia; which surgical airway?).

    Science.gov (United States)

    Bonanno, Fabrizio Giuseppe

    2012-10-01

    Which anesthesia for patients with critical airway? Safe and effective analgesia and anesthesia in critical airway is a skilled task especially after severe maxillofacial injury combined with head injury and hemorrhagic shock. If on one side sedation is wanted, on the other hand it may worsen the airway and hemodynamic situation to a point where hypoventilation and decrease of blood pressure, common side-effect of many opioids, may prejudice the patient's level of consciousness and hemodynamic compensation, compounding an already critical situation. What to do when endotracheal intubation fails and blood is trickling down the airways in an unconscious patient or when a conscious patient has to sit up to breathe? Which surgical airway in critical airway? Comparative studies among the various methods of emergency surgical airway would be unethical; furthermore, operator's training and experience is relevant for indications and performance. PMID:23248494

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    cells. The aim of the present in vivo study was to study the expression of porcine SP-D (pSP-D) in the lung during different pulmonary bacterial infections, and the effect of the routes of infection on this expression was elucidated. Furthermore, the aim was to study the in vivo spatial relationship...... pyogenes and Streptococcus suis serotype 2, respectively. By comparing normal and diseased lung tissue from the same lungs, increased diffuse pSP-D immunoreactivity was seen in the surfactant in both acute and chronic bronchopneumonias, while such increased expression of pSP-D was generally not present in...

  19. Modulating the Substrate Selectivity of DNA Aptamers Using Surfactants.

    Science.gov (United States)

    Peterson, Amberlyn M; Jahnke, Frank M; Heemstra, Jennifer M

    2015-11-01

    Nucleic acid aptamers have a number of advantages compared to antibodies, including greater ease of production and increased thermal stability. We hypothesized that aptamers may also be capable of functioning in the presence of high concentrations of surfactants, which readily denature antibodies and other protein-based affinity reagents. Here we report the first systematic investigation into the compatibility of DNA aptamers with surfactants. We find that neutral and anionic surfactants have only a minor impact on the ability of aptamers to fold and bind hydrophilic target molecules. Additionally, we demonstrate that surfactants can be utilized to modulate the substrate binding preferences of aptamers, likely due to the sequestration of hydrophobic target molecules within micelles. The compatibility of aptamers with commonly used surfactants is anticipated to expand their scope of potential applications, and the ability to modulate the substrate binding preferences of aptamers using a simple additive provides a novel route to increasing their selectivity in analytical applications. PMID:26465173

  20. Upper airway evaluation

    International Nuclear Information System (INIS)

    The authors are evaluating upper-airway sleep disorders with magnetic resonance (MR) imaging and x-ray cine computed tomography (CT). Fixed structural anatomy is visualized with multisection spin-echo MR imaging, the dynamic component with cine CT. Unique aspects of the study are described in this paper

  1. Methods of airway resistance assessment.

    Science.gov (United States)

    Urbankowski, Tomasz; Przybyłowski, Tadeusz

    2016-01-01

    Airway resistance is the ratio of driving pressure to the rate of the airflow in the airways. The most frequent methods used to measure airway resistance are whole-body plethysmography, the interrupter technique and the forced oscillation technique. All these methods allow to measure resistance during respiration at the level close to tidal volume, they do not require forced breathing manoeuvres or deep breathing during measurement. The most popular method for measuring airway resistance is whole-body plethysmography. The results of plethysmography include among others the following parameters: airway resistance (Raw), airway conductance (Gaw), specific airway resistance (sRaw) and specific airway conductance (sGaw). The interrupter technique is based on the assumption that at the moment of airway occlusion, air pressure in the mouth is equal to the alveolar pressure . In the forced oscillation technique (FOT), airway resistance is calculated basing on the changes in pressure and flow caused by air vibration. The methods for measurement of airway resistance that are described in the present paper seem to be a useful alternative to the most common lung function test - spirometry. The target group in which these methods may be widely used are particularly the patients who are unable to perform spirometry. PMID:27238174

  2. DIFFICULT AIRWAY IN THYROID SURGERY

    Directory of Open Access Journals (Sweden)

    Cuello-Azcárate JJ

    2011-12-01

    Full Text Available Background: Thyroid surgery has been considered as a risk factor for the management of difficult airway.Method: We review the relevant literature related to the difficult airway and thyroid surgery.Comments: Endothoracic goiter, deformity of the airway, compression of the airway and thyroid cancer do not appear to have an influence on the difficulty for intubation.Classical parameters have a better predictive value: mouth opening less than 35 mm, Mallampati II-IV, short neck, neck movility less than 80 degrees, thyromental distance less than 60 mm, retrognathia, Cormack index III-IV, macroglossia, inability to protude the teeth and body mass index (BMI greater than 35 Kg/m2.Conclusions: According to the literature, thyroid disease does not increase the risk for a difficult airway (ventilation / intubation.The risk of an unexpected difficult airway (false negative cannot be eliminated.All patients must undergo an assessment of the airway

  3. Supraglottic airway devices in children

    Science.gov (United States)

    Ramesh, S; Jayanthi, R

    2011-01-01

    Modern anaesthesia practice in children was made possible by the invention of the endotracheal tube (ET), which made lengthy and complex surgical procedures feasible without the disastrous complications of airway obstruction, aspiration of gastric contents or asphyxia. For decades, endotracheal intubation or bag-and-mask ventilation were the mainstays of airway management. In 1983, this changed with the invention of the laryngeal mask airway (LMA), the first supraglottic airway device that blended features of the facemask with those of the ET, providing ease of placement and hands-free maintenance along with a relatively secure airway. The invention and development of the LMA by Dr. Archie Brain has had a significant impact on the practice of anaesthesia, management of the difficult airway and cardiopulmonary resuscitation in children and neonates. This review article will be a brief about the clinical applications of supraglottic airways in children. PMID:22174464

  4. Management of the Traumatized Airway.

    Science.gov (United States)

    Jain, Uday; McCunn, Maureen; Smith, Charles E; Pittet, Jean-Francois

    2016-01-01

    There is a lack of evidence-based approach regarding the best practice for airway management in patients with a traumatized airway. General recommendations for the management of the traumatized airway are summarized in table 5. Airway trauma may not be readily apparent, and its evaluation requires a high level of suspicion for airway disruption and compression. For patients with facial trauma, control of the airway may be significantly impacted by edema, bleeding, inability to clear secretions, loss of bony support, and difficulty with face mask ventilation. With the airway compression from neck swelling or hematoma, intubation attempts can further compromise the airway due to expanding hematoma. For patients with airway disruption, the goal is to pass the tube across the injured area without disrupting it or to insert the airway distal to the injury using a surgical approach. If airway injury is extensive, a surgical airway distal to the site of injury may be the best initial approach. Alternatively, if orotracheal intubation is chosen, spontaneous ventilation may be maintained or RSI may be performed. RSI is a common approach. Thus, some of the patients intubated may subsequently require tracheostomy. A stable patient with limited injuries may not require intubation but should be watched carefully for at least several hours. Because of a paucity of evidence-based data, the choice between these approaches and the techniques utilized is a clinical decision depending on the patient's condition, clinical setting, injuries to airway and other organs, and available personnel, expertise, and equipment. Inability to obtain a definitive airway is always an absolute indication for an emergency cricothyroidotomy or surgical tracheostomy. PMID:26517857

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

    Directory of Open Access Journals (Sweden)

    Morgan Carrie I

    2011-12-01

    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

  6. Synthetic pulmonary surfactant preparations: new developments and future trends.

    Science.gov (United States)

    Mingarro, Ismael; Lukovic, Dunja; Vilar, Marçal; Pérez-Gil, Jesús

    2008-01-01

    Pulmonary surfactant is a lipid-protein complex that coats the interior of the alveoli and enables the lungs to function properly. Upon its synthesis, lung surfactant adsorbs at the interface between the air and the hypophase, a capillary aqueous layer covering the alveoli. By lowering and modulating surface tension during breathing, lung surfactant reduces respiratory work of expansion, and stabilises alveoli against collapse during expiration. Pulmonary surfactant deficiency, or dysfunction, contributes to several respiratory pathologies, such as infant respiratory distress syndrome (IRDS) in premature neonates, and acute respiratory distress syndrome (ARDS) in children and adults. The main clinical exogenous surfactants currently in use to treat some of these pathologies are essentially organic extracts obtained from animal lungs. Although very efficient, natural surfactants bear serious defects: i) they could vary in composition from batch to batch; ii) their production involves relatively high costs, and sources are limited; and iii) they carry a potential risk of transmission of animal infectious agents and the possibility of immunological reaction. All these caveats justify the necessity for a highly controlled synthetic material. In the present review the efforts aimed at new surfactant development, including the modification of existing exogenous surfactants by adding molecules that can enhance their activity, and the progress achieved in the production of completely new preparations, are discussed. PMID:18288994

  7. The oscillatory motion of a surfactant-laden liquid plug in a 2D-channel

    Science.gov (United States)

    Fujioka, Hideki; Grotberg, James B.

    2004-11-01

    Liquid plugs can form in the lung's small airways near the end of expiration. This happens more frequently when the amount of pulmonary surfactant is reduced. In medical treatments such as surfactant replacement therapy, partial liquid ventilation, and drug delivery, the formation of plugs in an airway is important to deliver the instilled liquid uniformly throughout the lung. In this study, we investigate numerically the oscillatory motion of a surfactant-laden liquid plug within a two-dimensional channel lined by a thin liquid film. The viscosity of both the left and right air phases is assumed to be negligible, so that the only fluid dynamics of the liquid phase is considered. The plug motion is regulated by the flow rate in the left air phase, which is prescribed as a sinusoidal function of time. The pressure drop between the left and right air phases varies for time with a different phase of the flow rate. The plug length and the film thickness oscillate with an average value during a cycle. These behaviors changes by system parameters, Reynolds number, Womersley number, Capillary number, and surfactant properties. The significance of this study on mechanical stresses acting on airway epithelial cells caused by the motion of a liquid plug during normal breath, conventional or high-frequency ventilation is discussed. Supported by NIH grant HL41126, NASA grant NAG3-2740.

  8. Matrix metalloproteinase expression and activity in human airway smooth muscle cells

    OpenAIRE

    Elshaw, Shona R.; Henderson, Neil; Knox, Alan J; Watson, Susan A.; Buttle, David J.; Johnson, Simon R

    2004-01-01

    Airway remodelling is a feature of chronic asthma comprising smooth muscle hypertrophy and deposition of extracellular matrix (ECM) proteins. Matrix metalloproteinases (MMPs) breakdown ECM, are involved in tissue remodelling and have been implicated in airway remodelling. Although mesenchymal cells are an important source of MMPs, little data are available on airway smooth muscle (ASM) derived MMPs. We therefore investigated MMP and tissue inhibitor of metalloproteinase (TIMP) production and ...

  9. Airways Disease: Phenotyping Heterogeneity Using Measures of Airway Inflammation

    OpenAIRE

    Siddiqui Salman; Brightling Christopher E

    2007-01-01

    Despite asthma and chronic obstructive pulmonary disease being widely regarded as heterogeneous diseases, a consensus for an accurate system of classification has not been agreed. Recent studies have suggested that the recognition of subphenotypes of airway disease based on the pattern of airway inflammation may be particularly useful in increasing our understanding of the disease. The use of non-invasive markers of airway inflammation has suggested the presence of four distinct phenotypes: ...

  10. Issues of critical airway management (Which anesthesia; which surgical airway?)

    OpenAIRE

    Fabrizio Giuseppe Bonanno

    2012-01-01

    Which anesthesia for patients with critical airway? Safe and effective analgesia and anesthesia in critical airway is a skilled task especially after severe maxillofacial injury combined with head injury and hemorrhagic shock. If on one side sedation is wanted, on the other hand it may worsen the airway and hemodynamic situation to a point where hypoventilation and decrease of blood pressure, common side-effect of many opioids, may prejudice the patient′s level of consciousness and hemodynami...

  11. Functional Effects of WNT1-Inducible Signaling Pathway Protein-1 on Bronchial Smooth Muscle Cell Migration and Proliferation in OVA-Induced Airway Remodeling.

    Science.gov (United States)

    Yang, Mingjin; Du, Yuejun; Xu, Zhibo; Jiang, Youfan

    2016-02-01

    Upregulation of WISP1 has been demonstrated in lung remodeling. Moreover, it has been recently found that some signaling components of WNT pathway can activate GSK3β signaling to mediate remodeling of airway smooth muscle (ASM) in asthma. Therefore, we hypothesized that WISP1, a signaling molecule downstream of the WNT signaling pathway, is involved in PI3K/GSK3β signaling to mediate ASM remodeling in asthma. Our results showed that WISP1 depletion partly suppressed OVA-induced ASM hypertrophy in vivo. In vitro, WISP1 could induce hBSMC hypertrophy and proliferation, accompanied by upregulation of levels of PI3K, p-Akt, p-GSK3β, and its own expression. TGF-β treatment could increase expression of PI3K, p-Akt, p-GSK3β, and WISP1. SH-5 treatment could partly suppress TGF-β-induced hypertrophy and proliferation of hBSMC, and depress expression of p-GSK3β and WISP1. In conclusion, WISP1 may be a potential inducer of ASM proliferation and hypertrophy in asthma. The pro-remodeling effect of WISP1 is likely due to be involved in PI3K-GSK3β-dependent noncanonical TGF-β signaling. PMID:26242865

  12. Airway epithelial cell tolerance to Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Verghese Margrith W

    2005-04-01

    Full Text Available Abstract Background The respiratory tract epithelium is a critical environmental interface that regulates inflammation. In chronic infectious airway diseases, pathogens may permanently colonize normally sterile luminal environments. Host-pathogen interactions determine the intensity of inflammation and thus, rates of tissue injury. Although many cells become refractory to stimulation by pathogen products, it is unknown whether the airway epithelium becomes either tolerant or hypersensitive in the setting of chronic infection. Our goals were to characterize the response of well-differentiated primary human tracheobronchial epithelial cells to Pseudomonas aeruginosa, to understand whether repeated exposure induced tolerance and, if so, to explore the mechanism(s. Methods The apical surface of well-differentiated primary human tracheobronchial epithelial cell cultures was repetitively challenged with Pseudomonas aeruginosa culture filtrates or the bacterial media control. Toxicity, cytokine production, signal transduction events and specific effects of dominant negative forms of signaling molecules were examined. Additional experiments included using IL-1β and TNFα as challenge agents, and performing comparative studies with a novel airway epithelial cell line. Results An initial challenge of the apical surface of polarized human airway epithelial cells with Pseudomonas aeruginosa culture filtrates induced phosphorylation of IRAK1, JNK, p38, and ERK, caused degradation of IκBα, generation of NF-κB and AP-1 transcription factor activity, and resulted in IL-8 secretion, consistent with activation of the Toll-like receptor signal transduction pathway. These responses were strongly attenuated following a second Pseudomonas aeruginosa, or IL-1β, but not TNFα, challenge. Tolerance was associated with decreased IRAK1 protein content and kinase activity and dominant negative IRAK1 inhibited Pseudomonas aeruginosa -stimulated NF-κB transcriptional

  13. Surfactant and adhesive formulations from alkaline biomass extracts

    Science.gov (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.

  14. cDNA and deduced amino acid sequence of human pulmonary surfactant-associated proteolipid SPL(Phe).

    OpenAIRE

    Glasser, S W; Korfhagen, T R; Weaver, T.; Pilot-Matias, T; Fox, J L; Whitsett, J A

    1987-01-01

    Hydrophobic surfactant-associated protein of Mr 6000-14,000 was isolated from ether/ethanol or chloroform/methanol extracts of mammalian pulmonary surfactant. Automated Edman degradation in a gas-phase sequencer showed the major N-terminus of the human low molecular weight protein to be Phe-Pro-Ile-Pro-Leu-Pro-Tyr-Cys-Trp-Leu-Cys-Arg-Ala-Leu-. Because of the N-terminal phenylalanine, the surfactant protein was designated SPL(Phe). Antiserum generated against hydrophobic surfactant protein(s) ...

  15. Brachycephalic airway syndrome.

    Science.gov (United States)

    Meola, Stacy D

    2013-08-01

    Brachycephalic airway syndrome is a common finding in brachycephalic breeds. A combination of primary and secondary changes can progress to life-threatening laryngeal collapse. Early recognition of primary anatomic abnormalities that include stenotic nares, elongated soft palate, and hypoplastic trachea would allow the clinician to make early recommendations for medical and surgical management, which can improve the quality of life in affected animals. PMID:24182996

  16. Lipids in airway secretions

    International Nuclear Information System (INIS)

    Lipids form a significant portion of airway mucus yet they have not received the same attention that epithelial glycoproteins have. We have analysed, by thin layer chromatography, lipids present in airway mucus under 'normal' and hypersecretory (pathological) conditions.The 'normals' included (1) bronchial lavage obtained from healthy human volunteers and from dogs and (2) secretions produced ''in vitro'' by human (bronchial) and canine (tracheal) explants. Hypersecretory mucus samples included (1) lavage from dogs made bronchitic by exposure to SO2, (2) bronchial aspirates from acute and chronic tracheostomy patients, (3) sputum from patients with cystic fibrosis and chronic bronchitis and (4) postmortem secretions from patients who died from sudden infant death syndrome (SIDS) or from status asthmaticus. Cholesterol was found to be the predominant lipid in 'normal' mucus with lesser amounts of phospholipids. No glycolipids were detected. In the hypersecretory mucus, in addition to neutral and phospholipids, glycolipids were present in appreciable amounts, often the predominant species, suggesting that these may be useful as markers of disease. Radioactive precursors 14C acetate and 14C palmitate were incorporated into lipids secreted ''in vitro'' by canine tracheal explants indicating that they are synthesised by the airway. (author)

  17. Lipids in airway secretions

    Energy Technology Data Exchange (ETDEWEB)

    Bhaskar, K.R.; DeFeudis O' Sullivan, D.; Opaskar-Hincman, H.; Reid, L.M.

    1987-01-01

    Lipids form a significant portion of airway mucus yet they have not received the same attention that epithelial glycoproteins have. We have analysed, by thin layer chromatography, lipids present in airway mucus under 'normal' and hypersecretory (pathological) conditions.The 'normals' included (1) bronchial lavage obtained from healthy human volunteers and from dogs and (2) secretions produced ''in vitro'' by human (bronchial) and canine (tracheal) explants. Hypersecretory mucus samples included (1) lavage from dogs made bronchitic by exposure to SO/sub 2/, (2) bronchial aspirates from acute and chronic tracheostomy patients, (3) sputum from patients with cystic fibrosis and chronic bronchitis and (4) postmortem secretions from patients who died from sudden infant death syndrome (SIDS) or from status asthmaticus. Cholesterol was found to be the predominant lipid in 'normal' mucus with lesser amounts of phospholipids. No glycolipids were detected. In the hypersecretory mucus, in addition to neutral and phospholipids, glycolipids were present in appreciable amounts, often the predominant species, suggesting that these may be useful as markers of disease. Radioactive precursors /sup 14/C acetate and /sup 14/C palmitate were incorporated into lipids secreted ''in vitro'' by canine tracheal explants indicating that they are synthesised by the airway.

  18. Upper airway resistance syndrome.

    Science.gov (United States)

    Hasan, N; Fletcher, E C

    1998-07-01

    Many clinicians are familiar with the clinical symptoms and signs of obstructive sleep apnea (OSA). In its most blatant form, OSA is complete airway obstruction with repetitive, prolonged pauses in breathing, arterial oxyhemoglobin desaturation; followed by arousal with resumption of breathing. Daytime symptoms of this disorder include excessive daytime somnolence, intellectual dysfunction, and cardiovascular effects such as systemic hypertension, angina, myocardial infarction, and stroke. It has been recently recognized that increased pharyngeal resistance with incomplete obstruction can lead to a constellation of symptoms identical to OSA called "upper airway resistance syndrome" (UARS). The typical findings of UARS on sleep study are: (1) repetitive arousals from EEG sleep coinciding with a (2) waxing and waning of the respiratory airflow pattern and (3) increased respiratory effort as measured by esophageal pressure monitoring. There may be few, if any, obvious apneas or hypopneas with desaturation, but snoring may be a very prominent finding. Treatment with nasal positive airway pressure (NCPAP) eliminates the symptoms and confirms the diagnosis. Herein we describe two typical cases of UARS. PMID:9676067

  19. Activity and biophysical inhibition resistance of a novel synthetic lung surfactant containing Super-Mini-B DATK peptide

    OpenAIRE

    Notter, Robert H.; Wang, Zhengdong; Walther, Frans J

    2016-01-01

    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 lu...

  20. The unusual symmetric reopening effect induced by pulmonary surfactant

    OpenAIRE

    Yamaguchi, Eiichiro; Giannetti, Matthew J.; Van Houten, Matthew J.; Forouzan, Omid; Shevkoplyas, Sergey S.; Gaver, Donald P.

    2014-01-01

    This study investigates the stability of a finger of air as it propagates into a liquid-filled model of a liquid-filled model of a pulmonary bifurcation. We seek to elucidate the stability characteristics of the reopening of daughter airways, an event that may be important to the treatment of acute lung disease. To do so, we investigated the symmetry of reopening under conditions of nearly constant surface tension with 1) purified H2O or 2) an anionic surfactant (sodium dodecyl sulfate). Dyna...