Pulmonary surfactant in health and human lung diseases: state of the art

Pulmonary surfactant is a complex and highly surface active material composed of lipids and proteins which is found in the fluid lining the alveolar surface of the lungs. Surfactant prevents alveolar collapse at low lung volume, and preserves bronchiolar patency during normal and forced respiration (biophysical functions). In addition, it is involved in the protection of the lungs from injuries and infections caused by inhaled particles and micro-organisms (immunological, non-biophysical functions). Pulmonary surfactant can only be harvested by lavage procedures, which may disrupt its pre-existing biophysical and biochemical micro-organization. These limitations must always be considered when interpreting ex vivo studies of pulmonary surfactant. A pathophysiological role for surfactant was first appreciated in premature infants with respiratory distress syndrome and hyaline membrane disease, a condition which is nowadays routinely treated with exogenous surfactant replacement. Biochemical surfactant abnormalities of varying degrees have been described in obstructive lung diseases (asthma, bronchiolitis, chronic obstructive pulmonary disease, and following lung transplantation), infectious and suppurative lung diseases (cystic fibrosis, pneumonia, and human immunodeficiency virus), adult respiratory distress syndrome, pulmonary oedema, other diseases specific to infants (chronic lung disease of prematurity, and surfactant protein-B deficiency), interstitial lung diseases (sarcoidosis, idiopathic pulmonary fibrosis, and hypersensitivity pneumonitis), pulmonary alveolar proteinosis, following cardiopulmonary bypass, and in smokers. For some pulmonary conditions surfactant replacement therapy is on the horizon, but for the majority much more needs to be learnt about the pathophysiological role the observed surfactant abnormalities may have.

This article has been cited by other articles:

				S. Uhlig and E. Gulbins Sphingolipids in the Lungs Am. J. Respir. Crit. Care Med., December 1, 2008; 178(11): 1100 - 1114. [Abstract] [Full Text] [PDF]

				D. Jain, E. N. Atochina-Vasserman, Y. Tomer, H. Kadire, and M. F. Beers Surfactant Protein D Protects against Acute Hyperoxic Lung Injury Am. J. Respir. Crit. Care Med., October 15, 2008; 178(8): 805 - 813. [Abstract] [Full Text] [PDF]

				M. G. Foreman, D. L. DeMeo, C. P. Hersh, V. J. Carey, V. S. Fan, J. J. Reilly, S. D. Shapiro, and E. K. Silverman Polymorphic variation in surfactant protein B is associated with COPD exacerbations Eur. Respir. J., October 1, 2008; 32(4): 938 - 944. [Abstract] [Full Text] [PDF]

				I. Garcia-Verdugo, A. Ravasio, E. G. de Paco, M. Synguelakis, N. Ivanova, J. Kanellopoulos, and T. Haller Long-term exposure to LPS enhances the rate of stimulated exocytosis and surfactant secretion in alveolar type II cells and upregulates P2Y2 receptor expression Am J Physiol Lung Cell Mol Physiol, October 1, 2008; 295(4): L708 - L717. [Abstract] [Full Text] [PDF]

				Y. Y. Zuo, S. M. Tadayyon, E. Keating, L. Zhao, R. A. W. Veldhuizen, N. O. Petersen, M. W. Amrein, and F. Possmayer Atomic Force Microscopy Studies of Functional and Dysfunctional Pulmonary Surfactant Films, II: Albumin-Inhibited Pulmonary Surfactant Films and the Effect of SP-A Biophys. J., September 15, 2008; 95(6): 2779 - 2791. [Abstract] [Full Text] [PDF]

				D. D. Sin, S. F. P. Man, D. D. Marciniuk, G. Ford, M. FitzGerald, E. Wong, E. York, R. R. Mainra, W. Ramesh, L. S. Melenka, et al. The Effects of Fluticasone with or without Salmeterol on Systemic Biomarkers of Inflammation in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., June 1, 2008; 177(11): 1207 - 1214. [Abstract] [Full Text] [PDF]

				J. Sadovski, T. Kuchenbuch, C. Ruppert, A. Fehrenbach, M. Hirschburger, W. Padberg, A. Gunther, J. M. Hohlfeld, H. Fehrenbach, and V. Grau Keratinocyte growth factor prevents intra-alveolar oedema in experimental lung isografts Eur. Respir. J., January 1, 2008; 31(1): 21 - 28. [Abstract] [Full Text] [PDF]

				W. K. Steagall, J.-P. Lin, and J. Moss The C/A(-18) polymorphism in the surfactant protein B gene influences transcription and protein levels of surfactant protein B Am J Physiol Lung Cell Mol Physiol, February 1, 2007; 292(2): L448 - L453. [Abstract] [Full Text] [PDF]

				M. Ochs Stereological analysis of acute lung injury Eur. Respir. Rev., December 1, 2006; 15(101): 115 - 121. [Abstract] [Full Text] [PDF]

				K. Nag, K. M. W. Keough, and M. R. Morrow Probing Perturbation of Bovine Lung Surfactant Extracts by Albumin using DSC and 2H-NMR Biophys. J., May 15, 2006; 90(10): 3632 - 3642. [Abstract] [Full Text] [PDF]

				R. Koetzler, M. Saifeddine, Z. Yu, F.S. Schurch, M. D. Hollenberg, and F. H. Y. Green Surfactant as an Airway Smooth Muscle Relaxant Am. J. Respir. Cell Mol. Biol., May 1, 2006; 34(5): 609 - 615. [Abstract] [Full Text] [PDF]

				A. Wemhoner, M. Frick, P. Dietl, P. Jennings, and T. Haller A Fluorescent Microplate Assay for Exocytosis in Alveolar Type II Cells J Biomol Screen, April 1, 2006; 11(3): 286 - 295. [Abstract] [PDF]

				S. G. Kallapur, T. J. M. Moss, M. Ikegami, R. L. Jasman, J. P. Newnham, and A. H. Jobe Recruited Inflammatory Cells Mediate Endotoxin-induced Lung Maturation in Preterm Fetal Lambs Am. J. Respir. Crit. Care Med., November 15, 2005; 172(10): 1315 - 1321. [Abstract] [Full Text] [PDF]

				S. L. Seurynck, N. J. Brown, C. W. Wu, K. W. Germino, E. K. Kohlmeir, E. P. Ingenito, M. R. Glucksberg, A. E. Barron, and M. Johnson Optical monitoring of bubble size and shape in a pulsating bubble surfactometer J Appl Physiol, August 1, 2005; 99(2): 624 - 633. [Abstract] [Full Text] [PDF]

				T. Madan, K. B. M. Reid, M. Singh, P. U. Sarma, and U. Kishore Susceptibility of Mice Genetically Deficient in the Surfactant Protein (SP)-A or SP-D Gene to Pulmonary Hypersensitivity Induced by Antigens and Allergens of Aspergillus fumigatus J. Immunol., June 1, 2005; 174(11): 6943 - 6954. [Abstract] [Full Text] [PDF]

				A. Braun, M. Steinecker, S. Schumacher, and M. Griese Surfactant function in children with chronic airway inflammation J Appl Physiol, December 1, 2004; 97(6): 2160 - 2165. [Abstract] [Full Text] [PDF]

				K. Nag, K. Rodriguez-Capote, A. K. Panda, L. Frederick, S. A. Hearn, N. O. Petersen, S. Schurch, and F. Possmayer Disparate effects of two phosphatidylcholine binding proteins, C-reactive protein and surfactant protein A, on pulmonary surfactant structure and function Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1145 - L1153. [Abstract] [Full Text] [PDF]

				M. Griese, R. Essl, R. Schmidt, E. Rietschel, F. Ratjen, M. Ballmann, K. Paul, and for the BEAT Study Group Pulmonary Surfactant, Lung Function, and Endobronchial Inflammation in Cystic Fibrosis Am. J. Respir. Crit. Care Med., November 1, 2004; 170(9): 1000 - 1005. [Abstract] [Full Text] [PDF]

				E. N. Atochina, J. M. Beck, A. M. Preston, A. Haczku, Y. Tomer, S. T. Scanlon, T. Fusaro, J. Casey, S. Hawgood, A. J. Gow, et al. Enhanced Lung Injury and Delayed Clearance of Pneumocystis carinii in Surfactant Protein A-Deficient Mice: Attenuation of Cytokine Responses and Reactive Oxygen-Nitrogen Species Infect. Immun., October 1, 2004; 72(10): 6002 - 6011. [Abstract] [Full Text] [PDF]

				J. A. Whitsett, C. J. Bachurski, K. C. Barnes, P. A. Bunn Jr., L. M. Case, D. N. Cook, D. Crooks, M. W. Duncan, L. Dwyer-Nield, R. C. Elston, et al. Functional Genomics of Lung Disease Am. J. Respir. Cell Mol. Biol., August 1, 2004; 31(2/S1): S1 - S81. [Full Text] [PDF]

				J. F. Lewis and R. A. W. Veldhuizen Analyzing Surfactant Metabolism in Humans: An Important First Step Am. J. Respir. Crit. Care Med., July 1, 2004; 170(1): 2 - 3. [Full Text] [PDF]

				A. K. Panda, K. Nag, R. R. Harbottle, K. Rodriguez-Capote, R. A. W. Veldhuizen, N. O. Petersen, and F. Possmayer Effect of Acute Lung Injury on Structure and Function of Pulmonary Surfactant Films Am. J. Respir. Cell Mol. Biol., May 1, 2004; 30(5): 641 - 650. [Abstract] [Full Text] [PDF]

				D. S. Phelps, T. M. Umstead, M. Mejia, G. Carrillo, A. Pardo, and M. Selman Increased Surfactant Protein-A Levels in Patients With Newly Diagnosed Idiopathic Pulmonary Fibrosis Chest, February 1, 2004; 125(2): 617 - 625. [Abstract] [Full Text] [PDF]

				B. Raychaudhuri, S. Abraham, T. L. Bonfield, A. Malur, A. Deb, J. A. DiDonato, M. S. Kavuru, and M. J. Thomassen Surfactant Blocks Lipopolysaccharide Signaling by Inhibiting both Mitogen-Activated Protein and I{kappa}B Kinases in Human Alveolar Macrophages Am. J. Respir. Cell Mol. Biol., February 1, 2004; 30(2): 228 - 232. [Abstract] [Full Text] [PDF]

				E. Lappi-Blanco, R. Kaarteenaho-Wiik, S. Salo, R. Sormunen, M. Maatta, H. Autio-Harmainen, Y. Soini, and P. Paakko Laminin-5 {gamma}2 Chain in Cryptogenic Organizing Pneumonia and Idiopathic Pulmonary Fibrosis Am. J. Respir. Crit. Care Med., January 1, 2004; 169(1): 27 - 33. [Abstract] [Full Text]

				F. Brasch, M. Ochs, T. Kahne, S. Guttentag, V. Schauer-Vukasinovic, M. Derrick, G. Johnen, N. Kapp, K.-M. Muller, J. Richter, et al. Involvement of Napsin A in the C- and N-terminal Processing of Surfactant Protein B in Type-II Pneumocytes of the Human Lung J. Biol. Chem., December 5, 2003; 278(49): 49006 - 49014. [Abstract] [Full Text] [PDF]

				A. Gunther, N. Lubke, M. Ermert, R. T. Schermuly, N. Weissmann, A. Breithecker, P. Markart, C. Ruppert, K. Quanz, L. Ermert, et al. Prevention of Bleomycin-induced Lung Fibrosis by Aerosolization of Heparin or Urokinase in Rabbits Am. J. Respir. Crit. Care Med., December 1, 2003; 168(11): 1358 - 1365. [Abstract] [Full Text] [PDF]

				T. L. Bonfield, C. F. Farver, B. P. Barna, A. Malur, S. Abraham, B. Raychaudhuri, M. S. Kavuru, and M. J. Thomassen Peroxisome Proliferator-Activated Receptor-{gamma} Is Deficient in Alveolar Macrophages from Patients with Alveolar Proteinosis Am. J. Respir. Cell Mol. Biol., December 1, 2003; 29(6): 677 - 682. [Abstract] [Full Text] [PDF]

				M. Geiser and S. Bastian Surface-lining layer of airways in cystic fibrosis mice Am J Physiol Lung Cell Mol Physiol, December 1, 2003; 285(6): L1277 - L1285. [Abstract] [Full Text] [PDF]

				J. Zagorski, J. Debelak, M. Gellar, J. A. Watts, and J. A. Kline Chemokines Accumulate in the Lungs of Rats with Severe Pulmonary Embolism Induced by Polystyrene Microspheres J. Immunol., November 15, 2003; 171(10): 5529 - 5536. [Abstract] [Full Text] [PDF]

				B. E. Isakson, G. J. Seedorf, R. L. Lubman, W. H. Evans, and S. Boitano Cell-Cell Communication in Heterocellular Cultures of Alveolar Epithelial Cells Am. J. Respir. Cell Mol. Biol., November 1, 2003; 29(5): 552 - 561. [Abstract] [Full Text]

				L. G. Vazquez de Lara, T. M. Umstead, S. E. Davis, and D. S. Phelps Surfactant protein A increases matrix metalloproteinase-9 production by THP-1 cells Am J Physiol Lung Cell Mol Physiol, October 1, 2003; 285(4): L899 - L906. [Abstract] [Full Text] [PDF]

				I. Tsangaris, M.E. Lekka, E. Kitsiouli, S. Constantopoulos, and G. Nakos Bronchoalveolar lavage alterations during prolonged ventilation of patients without acute lung injury Eur. Respir. J., March 1, 2003; 21(3): 495 - 501. [Abstract] [Full Text] [PDF]

				M. Griese, M. Neumann, T. von Bredow, R. Schmidt, and F. Ratjen Surfactant in children with malignancies, immunosuppression, fever and pulmonary infiltrates Eur. Respir. J., November 1, 2002; 20(5): 1284 - 1291. [Abstract] [Full Text] [PDF]

				R. W. Vandivier, C. A. Ogden, V. A. Fadok, P. R. Hoffmann, K. K. Brown, M. Botto, M. J. Walport, J. H. Fisher, P. M. Henson, and K. E. Greene Role of Surfactant Proteins A, D, and C1q in the Clearance of Apoptotic Cells In Vivo and In Vitro: Calreticulin and CD91 as a Common Collectin Receptor Complex J. Immunol., October 1, 2002; 169(7): 3978 - 3986. [Abstract] [Full Text] [PDF]

				A. Haczku, E. N. Atochina, Y. Tomer, Y. Cao, C. Campbell, S. T. Scanlon, S. J. Russo, G. Enhorning, and M. F. Beers The late asthmatic response is linked with increased surface tension and reduced surfactant protein B in mice Am J Physiol Lung Cell Mol Physiol, October 1, 2002; 283(4): L755 - L765. [Abstract] [Full Text] [PDF]

				T. A. Russo, L. A. Bartholomew, B. A. Davidson, J. D. Helinski, U. B. Carlino, P. R. Knight III, M. F. Beers, E. N. Atochina, R. H. Notter, and B. A. Holm Total extracellular surfactant is increased but abnormal in a rat model of gram-negative bacterial pneumonia Am J Physiol Lung Cell Mol Physiol, September 1, 2002; 283(3): L655 - L663. [Abstract] [Full Text] [PDF]

				L. Guillot, V. Balloy, F. X. McCormack, D. T. Golenbock, M. Chignard, and M. Si-Tahar Cutting Edge: The Immunostimulatory Activity of the Lung Surfactant Protein-A Involves Toll-Like Receptor 4 J. Immunol., June 15, 2002; 168(12): 5989 - 5992. [Abstract] [Full Text] [PDF]

				A. Q. Thomas, K. Lane, J. Phillips III, M. Prince, C. Markin, M. Speer, D. A. Schwartz, R. Gaddipati, A. Marney, J. Johnson, et al. Heterozygosity for a Surfactant Protein C Gene Mutation Associated with Usual Interstitial Pneumonitis and Cellular Nonspecific Interstitial Pneumonitis in One Kindred Am. J. Respir. Crit. Care Med., May 1, 2002; 165(9): 1322 - 1328. [Abstract] [Full Text] [PDF]

				K. Wassermann Is Asthma Another Interstitial Lung Disease? Chest, March 1, 2002; 121(3): 673 - 674. [Full Text] [PDF]

				K. J. Haley, A. Ciota, J. P. Contreras, M. R. Boothby, D. L. Perkins, and P. W. Finn Alterations in lung collectins in an adaptive allergic immune response Am J Physiol Lung Cell Mol Physiol, March 1, 2002; 282(3): L573 - L584. [Abstract] [Full Text] [PDF]

				M. Ochs, G. Johnen, K.-M. Muller, T. Wahlers, S. Hawgood, J. Richter, and F. Brasch Intracellular and Intraalveolar Localization of Surfactant Protein A (SP-A) in the Parenchymal Region of the Human Lung Am. J. Respir. Cell Mol. Biol., January 1, 2002; 26(1): 91 - 98. [Abstract] [Full Text] [PDF]

				M. Kendall, T. D. Tetley, E. Wigzell, B. Hutton, M. Nieuwenhuijsen, and P. Luckham Lung lining liquid modifies PM2.5 in favor of particle aggregation: a protective mechanism Am J Physiol Lung Cell Mol Physiol, January 1, 2002; 282(1): L109 - L114. [Abstract] [Full Text] [PDF]

				B. E. Isakson, R. L. Lubman, G. J. Seedorf, and S. Boitano Modulation of pulmonary alveolar type II cell phenotype and communication by extracellular matrix and KGF Am J Physiol Cell Physiol, October 1, 2001; 281(4): C1291 - C1299. [Abstract] [Full Text] [PDF]

				R. C. Savani, R. I. Godinez, M. H. Godinez, E. Wentz, A. Zaman, Z. Cui, P. M. Pooler, S. H. Guttentag, M. F. Beers, L. W. Gonzales, et al. Respiratory distress after intratracheal bleomycin: selective deficiency of surfactant proteins B and C Am J Physiol Lung Cell Mol Physiol, September 1, 2001; 281(3): L685 - L696. [Abstract] [Full Text] [PDF]

				A. Haczku, E. N. Atochina, Y. Tomer, H. Chen, S. T. Scanlon, S. Russo, J. Xu, R. A. Panettieri Jr., and M. F. Beers Aspergillus fumigatus-Induced Allergic Airway Inflammation Alters Surfactant Homeostasis and Lung Function in BALB/c Mice Am. J. Respir. Cell Mol. Biol., July 1, 2001; 25(1): 45 - 50. [Abstract] [Full Text] [PDF]

				L. Calderon-Garciduenas, A. Mora-Tiscareno, L. A. Fordham, C. J. Chung, R. Garcia, N. Osnaya, J. Hernandez, H. Acuna, T. M. Gambling, A. Villarreal-Calderon, et al. Canines as Sentinel Species for Assessing Chronic Exposures to Air Pollutants: Part 1. Respiratory Pathology Toxicol. Sci., June 1, 2001; 61(2): 342 - 355. [Abstract] [Full Text] [PDF]

				C. J. Bachurski, G. F. Ross, M. Ikegami, B. W. Kramer, and A. H. Jobe Intra-amniotic endotoxin increases pulmonary surfactant proteins and induces SP-B processing in fetal sheep Am J Physiol Lung Cell Mol Physiol, February 1, 2001; 280(2): L279 - L285. [Abstract] [Full Text] [PDF]

				M. Song and D. S. Phelps Interaction of Surfactant Protein A with Lipopolysaccharide and Regulation of Inflammatory Cytokines in the THP-1 Monocytic Cell Line Infect. Immun., December 1, 2000; 68(12): 6611 - 6617. [Abstract] [Full Text] [PDF]

				Y. Ashino, X. Ying, L. G. Dobbs, and J. Bhattacharya [Ca2+]i oscillations regulate type II cell exocytosis in the pulmonary alveolus Am J Physiol Lung Cell Mol Physiol, July 1, 2000; 279(1): L5 - L13. [Abstract] [Full Text] [PDF]

				M. Song and D. S. Phelps Comparison of SP-A and LPS effects on the THP-1 monocytic cell line Am J Physiol Lung Cell Mol Physiol, July 1, 2000; 279(1): L110 - L117. [Abstract] [Full Text] [PDF]