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Molecular Basis for Surfactant Function in ARDS

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Molecular Biology of Acute Lung Injury

Part of the book series: Molecular and Cellular Biology of Critical Care Medicine ((MCCM,volume 1))

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Abstract

While knowledge regarding the molecular and physiologic basis of surfactant function has been expanded primarily through study of the preterm lung, the pathogenesis of adult respiratory distress syndrome (ARDS) and the precise roles played by the surfactant system in this complex disorder have remained less well defined. Since ARDS is initiated by various systemic or lung injuries, the heterogeneity of mechanisms involved in the pathogenesis of ARDS are likely to be complex and involve numerous cellular pathways critical for lung function.

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References

  1. Goerke, J. (1998) Pulmonary surfactant: functions and molecular composition. Biochim Biophys Acta 1408, 79–89

    Article  PubMed  CAS  Google Scholar 

  2. Jobe, A.H., and Ikegami, M. (1997) Surfactant for acute respiratory distress syndrome. Adv Intern Med 42, 203–230

    PubMed  CAS  Google Scholar 

  3. Jobe, A.H. (1993) Pulmonary surfactant therapy. N Engl J Med 328, 861–868

    Article  PubMed  CAS  Google Scholar 

  4. Evans, D.A., Wilmott, R.W., and Whitsett, J.A. (1996) Surfactant replacement therapy for adult respiratory distress syndrome in children. Pediatr Pulmonol 21, 328–336

    Article  PubMed  CAS  Google Scholar 

  5. Weaver, T.E., and Conkright, J.J. (2001) Functions of surfactant proteins B and C. Annu Rev Physiol 63, 555–578

    Article  PubMed  CAS  Google Scholar 

  6. Nogee, L.M., de Mello, D.E., Dehner, L.P., and Colten, H.R. (1993) Brief report: deficiency of pulmonary surfactant protein B in congenital alveolar proteinosis. N Engl J Med 328, 406–410

    Article  PubMed  CAS  Google Scholar 

  7. Nogee, L.M., Dunbar, A.E., Wert, S.E., Askin, F., Hamvas, A., and Whitsett, J.A. (2001) A mutation in the surfactant protein C gene associated with familial interstitial lung disease. N Engl J Med 344, 573–579

    Article  PubMed  CAS  Google Scholar 

  8. Clark, J.C., Wert, S.E., Bachurski, C.J., Stahlman, M.T., Stripp, B.R., Weaver, T.E., and Whitsett, J.A. (1995) Targeted disruption of the surfactant protein B gene disrupts surfactant homeostasis, causing respiratory failure in newborn mice. Proc Natl Acad Sci USA 92, 7794–7798

    Article  PubMed  CAS  Google Scholar 

  9. Glasser, S.W., Burhans, M.S., Korfhagen, T.R., Na, C-L., Sly, P.D., Ross, G.F., Ikegami, M. and Whitsett, J.A. (2001) Altered stability of pulmonary surfactant in SP-C deficient mice. Proc Natl Acad Sci USA, (in press)

    Google Scholar 

  10. Vorbroker, D.K., Profitt, S.A., Nogee, L.M., and Whitsett, J.A. (1995) Aberrant processing of surfactant protein C (SP-C) in hereditary SP-B deficiency. Am J Physiol (Lung Cell Mol Physiol 12) 268, L647–L656

    CAS  Google Scholar 

  11. Tokieda, K., Whitsett, J.A., Clark, J.C., Weaver, T.E., Ikeda, K., Jobe, A.H., Ikegami, M, and Iwamoto, H.S. (1997) Pulmonary dysfunction in neonatal SP-B deficient mice. Am J Physiol (Lung Cell Mol Physiol) 273, L875–L882

    CAS  Google Scholar 

  12. Tokieda, K., Iwamoto, H.S., Bachurski, C., Wert, S.E., Hull, W.M., Ikeda, K., and Whitsett, J.A. (1999) Surfactant protein-B-deficient mice are susceptible to hyperoxic lung injury. Am J Respir Cell Mol Biol 21, 463–472

    PubMed  CAS  Google Scholar 

  13. Veldhuizen, R.A.W., McCaig, L.A., Akino, T., and Lewis, J.F. (1995) Pulmonary surfactant subfractions in patients with the acute respiratory distress syndrome. Am J Respir Crit Care Med 152, 1867–1871

    PubMed  CAS  Google Scholar 

  14. Gunther, A., Siebert, C., Schmidt, R., Ziegler, S., Grimminger, F., Yabut, M, Temmesfild, B., Walmrath, D., Morr, H., and Seeger, W. (1996) Surfactant alterations in severe pneumonia, acute respiratory distress syndrome, and cardiogenic lung edema. Am J Respir Crit Care Med 153, 176–184

    PubMed  CAS  Google Scholar 

  15. Nakos, G., Kitsiouli, E.I., Tsangaris, I., and Lekka, M.E. (1998) Bronchoalveolar lavage fluid characteristics of early intermediate and late phases of ARDS. Alterations in leukocytes, proteins, PAF and surfactant components. Intensive Care Med. 24, 296–303

    Article  PubMed  CAS  Google Scholar 

  16. Bersten, A.D., Doyle, I.R., Davidson, K.G., Barr, H.A., Nicholas, T.E., and Kermeen, F. (1998) Surfactant composition reflects lung over-inflation and arterial oxygenation in patients with acute lung injury. Eur Respir J 12, 301–308

    Article  PubMed  CAS  Google Scholar 

  17. LeVine, A.M., Lotze, A., Stanley, S., Stroud, C., O’Donnell, R., Whitsett, J., and Pollack, M.M. (1996) Surfactant content in children with inflammatory lung disease. Crit Care Med 24, 1062–1067

    Article  PubMed  CAS  Google Scholar 

  18. Greene, K.E., Wright, J.A., Steinberg, K.P., Ruzinski, J.T., Caldwell, E., Wong, W.B., Hull, W., Whitsett, J.A., Akino, T., Kuroki, Y., Nagae, H., Hudson, L.D., and Martin, T.R. (1999) Serial changes in surfactant-associated proteins in lung and serum before and after onset of ARDS. Am J Respir Crit Care Med 160, 1843–1850

    PubMed  CAS  Google Scholar 

  19. Baker, C.S., Evans, T.W., Randle, B.J., and Haslam, P.L. (1999) Damage to surfactant-specific protein in acute respiratory distress syndrome. Lancet 353, 1232–1237

    Article  PubMed  CAS  Google Scholar 

  20. Doyle, I.R., Bersten A.D., and Nicholas, T.E. (1997) Surfactant proteins-A and -B are elevated in plasma of patients with acute respiratory failure. Am J Respir Crit Care Med 156, 1217–1229

    PubMed  CAS  Google Scholar 

  21. Doyle, I.R., Nicholas, T.E., Bersten, A.D. (1995) Serum surfactant protein-A levels in patients with acute cardiogenic pulmonary edema and adult respiratory distress syndrome. Am J Respir Crit Care Med 152, 307–317

    PubMed  CAS  Google Scholar 

  22. Hafner, D., Beume, R., Killian, U., Krasznai, G., and Lachmann, B. (1995) Dose-response comparisons of five lung surfactant factor (LSF) preparations in an animal model of adult respiratory distress syndrome (ARDS). Br J Pharmacol 115, 451–458

    Article  PubMed  CAS  Google Scholar 

  23. Alvarez, F.J., Alfonso, L.F., Gastiasoro, E., Lopez-Heredia, J., Arnaiz, A., and Valls-Soler, A. (1995) The effects of multiple small doses of exogenous surfactant on experimental respiratory failure induced by lung lavage in rats. Acta Anaesthesiol Scand 39, 970–974

    Article  PubMed  CAS  Google Scholar 

  24. Makhoul, I.R., Kugelman, A., Bui, K.C., Berkeland, J.E., Saiki, K., Lew, C.D., and Garg, M. (1996) Reduction of respiratory system resistance of rabbits with surfactant deficiency using a novel ultra thin walled endotracheal tube. ASAIO J 42, 1000–1005

    Article  PubMed  CAS  Google Scholar 

  25. Sood, S.L., Balaraman, V., Finn, K.C., Wilderson, S.Y., Mundie, T.F., and Easa, D. (1996) Exogenous surfactant decreases oxygenation in Escherichia coli endotoxin-treated neonatal piglets. Pediatr Pulmonol 22, 376–386

    Article  PubMed  CAS  Google Scholar 

  26. Ito, Y., Manwell, S.E.E., Kerr, C.L., Veldhuizen, R.A.W., Yao, L.J., Bjarneson, D., McCaig, L.A., Bartlett, A.F., and Lewis, J.F. (1998) Effects of ventilation strategies on the efficacy of exogenous surfactant therapy in a rabbit model of acute lung injury. Am J Respir Crit Care Med 157, 145–155

    Google Scholar 

  27. Rosenthal, C., Caronia, C., Quinn, C., Lugo, N., and Sagy, M. (1998) A comparison among animal models of acute lung injury. Crit Care Med 26, 912–916

    Article  PubMed  CAS  Google Scholar 

  28. Gommers, D., Eijking, E.P., So, K.L., van’t Veen, A., and Lachmann, B. (1998) Bronchoalveolar lavage with a diluted surfactant suspension prior to surfactant instillation improves the effectiveness of surfactant therapy in experimental acute respiratory distress syndrome (ARDS). Intensive Care Med 24, 494–500

    Article  PubMed  CAS  Google Scholar 

  29. Lewis, L, McCaig, L., Hafner, D., Spragg, R., Veldhuizen, R., and Kerr, C. (1999) Dosing and delivery of a recombinant surfactant in lung-injured adult sheep. Am J Respir Crit Care Med 159, 741–747

    PubMed  CAS  Google Scholar 

  30. Puligandla, P.S., Gill, T., McCaig, L.A., Yao, L-J., Veldhuizen, R.A.W., Possmayer, F., and Lewis, J.F. (2000) Alveolar environment influences the metabolic and biophysical properties of exogenous surfactants. J Appl Physiol 88, 1061–1071

    Article  PubMed  CAS  Google Scholar 

  31. Schermuly, R.T., Gunther, A., Weissmann, N., Ghofrani, H.A., Seeger, W., Grimminger, F., and Walmrath, D. (2000) Differential impact of ultrasonically nebulized versus tracheal-instilled surfactant on ventilation-perfusion (VA/Q) mismatch in a model of acute lung injury. Am J Respir Crit Care Med 161, 152–159

    PubMed  CAS  Google Scholar 

  32. Tashiro, K., Yamada, K., Li, W.Z., Matsumoto, Y., and Kobayashi. T. (1996) Aerosolized and instilled surfactant therapies for acute lung injury caused by intratracheal endotoxin in rats. Crit Care Med 24, 488–494

    Article  PubMed  CAS  Google Scholar 

  33. Picone, A., Gatto, L.A., Nieman, G.F., Paskanik, A.M., and Lutz, C. (1996) Pulmonary surfactant function following endotoxin: effects of exogenous surfactant treatment. Shock 5, 304–310

    Article  PubMed  CAS  Google Scholar 

  34. Sood, S.L., Balaraman, V., Finn, K.C., Britton, B., Uyehara, C.F., and Easa, D. (1996) Exogenous surfactants in a piglet model of acute respiratory distress syndrome. Am J Respir Crit Care Med 153, 820–828

    PubMed  CAS  Google Scholar 

  35. van Helden, H.P., Kuijpers, W.C., Steenvoorden, D., Go, C., Bruijnzeel, P.L., van Eijk, M., and Haagsman, H.P. (1997) Intratracheal aerosolization of endotoxin (LPS) in the rat: a comprehensive animal model to study adult (acute) respiratory distress syndrome. Exp Lung Res 23, 297–316

    Article  PubMed  Google Scholar 

  36. Molloy, J., McCaig, L., Veldhuizen, R., Yao, L.J., Joseph, M., Whitsett, J., and Lewis, J. (1997) Alterations of the endogenous surfactant system in septic adult rats. Am J Respir Crit Care Med 156, 617–623

    Google Scholar 

  37. Holguin, F., Moss, I.M., Brown, L.A.S., and Guidot, D.M. (1998) Chronic ethanol ingestion impairs alveolar type II cell glutathione homeostasis and function and predisposes to endotoxin-mediated acute edematous lung injury in rats. J Clin Invest 101, 761–768

    Article  PubMed  CAS  Google Scholar 

  38. Lutz, C., Carney, D., Finck, C., Picone, A., Gatto, L.A., Paskanik, A., Langenback, E., and Nieman, G. (1998) Aerosolized surfactant improves pulmonary function in endotoxin0-induced lung injury. Am J Respir Crit Care Med 158, 840–845

    PubMed  CAS  Google Scholar 

  39. Mora, R., Arold, S., Marzan, Y., Suki, B., and Ingenito, E.P. (2000) Determinants of surfactant function in acute lung injury and early recovery. Am J Physiol Lung Cell Mol Physiol 279, L342–L349

    PubMed  CAS  Google Scholar 

  40. Novick, R.J., Gilpin, A.A., Gehman, K.E., Ali, I.S., Veldhuizen, R.A., Duplan, J., Denning, L., Possmayer, F., Bjarneson, D., and Lewis, J.F. (1997) Mitigation of injury in canine lung grafts by exogenous surfactant therapy. J Thorac Cardiovasc Surg 113, 342–353

    Article  PubMed  CAS  Google Scholar 

  41. Novotny, W. (1995) Hyperoxic lung injury reduces exogenous surfactant clearance in vivo. Am J Respir Crit Care Med 151, 1843–1847

    PubMed  CAS  Google Scholar 

  42. Shermuly, R., Schmehl, T., Gunther, A., Grimminger, F., Seeger, W., Walmrath, D. (1997) Ultrasonic nebulization for efficient delivery of surfactant in a model of acute lung injury. Am J Respir Crit Care Med 156, 445–453

    Google Scholar 

  43. Silva, M.F., and Saldiva, P.H. (1998) Paraquat poisoning: an experimental model of dose-dependent acute lung injury due to surfactant dysfunction. Braz J Mel Biol Res 31, 445–450

    Article  CAS  Google Scholar 

  44. Zhu, G.F., Sun, B., Niu, S.F., Cai, U.Y., Lin, K., Lindwall, R., and Robertson, B. (1998) Combined surfactant therapy and inhaled nitric oxide in rabbits with oleic acid-induced acute respiratory distress syndrome. Am J Respir Crit Care Med 158, 437–443

    PubMed  CAS  Google Scholar 

  45. Jacobs, B.R., Smith, D.J., Zingarelli, B., Passerini, D.J., Ballard, E.T., and Brilli, R.J. (2000) Soluble nitric oxide donor and surfactant improve oxygenation and pulmonary hypertension in porcine lung injury. Nitric Oxide 4, 412–422

    Article  PubMed  CAS  Google Scholar 

  46. Hafner, D., and Germann, P.G. (1999) A rat model of acute respiratory distress syndrome (ARDS) Part 2, influence of lavage volume, lavage repetition, and therapeutic treatment with rSP-C surfactant. J Pharmacol Toxicol Methods 41, 97–106

    Article  PubMed  CAS  Google Scholar 

  47. Zhou, Z.-H., Sun, B., Lin, K., and Zhu, L-W (2000) Prevention of rabbit acute lung injury by surfactant, inhaled nitric oxide, and pressure support ventilation. Am J Respir Crit Care Med 161, 581–588

    PubMed  CAS  Google Scholar 

  48. Veldhuizen, R.A., Tremblay, L.N., Govindarajan, A., van Rozendaal, B.A., Haagsman, H.P., and Slutsky, A.S. (2000) Pulmonary surfactant is altered during mechanical ventilation of isolated rat lung. Crit Care Med 28, 2545–2551

    Article  PubMed  CAS  Google Scholar 

  49. Lewis, J.F., and Veldhuizen, R.A. (1995) Factors influencing efficacy of exogenous surfactant in acute lung injury. Biol Neonate 67, 48–60

    Article  PubMed  CAS  Google Scholar 

  50. Robertson, B. (1998) Surfactant inactivation and surfactant therapy in acute respiratory distress syndrome (ARDS). Monaldi Arch Chest Dis 53, 64–69

    PubMed  CAS  Google Scholar 

  51. van Helden, H.P., Kuijpers, W.C., Langerwerf, P.E., Langen, R.C., Haagsman, H.P., and Bruijnzeel, P.L. (1998) Efficacy of Curosurf in a rat model of acute respiratory distress syndrome. Eur Respir J 12, 533–539

    Article  PubMed  Google Scholar 

  52. Tashiro, K., Nishizuka, K., Matsumoto, Y., Ohta, K., Suzuki, Y., and Kobagashi, T. (1999) Modified natural and synthetically reconstituted surfactant therapies for acute lung injury caused by endotoxin in rats. Acta Anaesthesiol Scand 43, 821–828

    Article  PubMed  CAS  Google Scholar 

  53. Hafner, D., Germann, P-G., and Hauschke, D. (1998) Comparison of rSP-C surfactant with natural and synthetic surfactants after late treatment in a rat model of the acute respiratory distress syndrome. Br J Pharmacol 124, 1083–1090

    Article  PubMed  CAS  Google Scholar 

  54. Hafner, D., Germann, P.G., Hauschke, D., and Killian, U. (1999) Effects of early treatment with rSP–C surfactant on oxygenation and histology in rats with acute lung injury. Pulm Pharmacol Ther 12, 193–201

    Article  PubMed  CAS  Google Scholar 

  55. Wiswell, T.E., Smith, R.M., Katz, L.B., Mastroianni, L., Wong, D.Y., Willms, D., Heard, S., Wilson, M., Hite, R.D., Anzueto, A., Revak, S.D., and Cochrane, C.G. (1999) Bronchopulmonary segmental lavage with surfactant (KL4-surfactant) for acute respiratory distress syndrome. Am J Respir Crit Care Med 160, 1188–1195

    PubMed  CAS  Google Scholar 

  56. Balaraman, V., Meister, J., Ku, T.L., Sood, S.L., Tarn, E., Killeen, J., Uyehara, C.F.T., Egan, E., and Easa, D. (1998) Lavage administration of dilute surfactants after acute lung injury in neonatal piglets. Am J Respir Crit Care Med 158, 12–17

    PubMed  CAS  Google Scholar 

  57. Cochrane, C.G., and Revak, S.D. (1999) Surfactant lavage treatment in a model of respiratory distress syndrome. Chest 116, 85S–87S

    Article  PubMed  Google Scholar 

  58. Verbrugge, S.J., Sorm, V., and Lachmann, B. (1997) Mechanisms of acute respiratory distress syndrome: role of surfactant changes and mechanical ventilation. J Physiol Pharmacol 48, 537–557

    PubMed  CAS  Google Scholar 

  59. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 342:1301–1308, 2000

    Article  Google Scholar 

  60. Spragg, R.G., Gilliard, N., Richman, P., Smith, R.M., Hite, R.D., Pappert, D., Robertson, B., Curstedt, T., and Strayer, D. (1994) Acute effects of a single dose of porcine surfactant on patients with the adult respiratory distress syndrome. Chest 105, 195–202

    Article  PubMed  CAS  Google Scholar 

  61. Perez-Benavides, F., Riff, E., and Franks, C. (1995) Adult respiratory distress syndrome and artificial surfactant replacement in the pediatric patient. Pediatr Emerg Care 11, 153–155

    Article  PubMed  CAS  Google Scholar 

  62. Willson, D.F., Jiao, J.H., Bauman, L.A., Zaritsky, A., Craft, H., Dockery, K., Conrad, D., and Dalton, H. (1996) Calf’s lung surfactant extract in acute hypoxemic respiratory failure in children. Crit Care Med 24, 1316–1322

    Article  PubMed  Google Scholar 

  63. Lopez-Herce, J., de Lucas, N., Carrillo, A., Bustinza, A., and Moral, R. (1999) Surfactant treatment for acute respiratory distress syndrome. Arch Dis Child 80, 248–252

    Article  PubMed  CAS  Google Scholar 

  64. Walmrath, D., Gunther, A., Ghofrani, H.A., Schermuly, R., Schneider, T., Grimminger, F., and Seeger, W. (1996) Bronchoscopic surfactant administration in patients with severe adult respiratory distress syndrome and sepsis. Am J Respir Crit Care Med 154, 57–62

    PubMed  CAS  Google Scholar 

  65. Gregory, T.J., Steinberg, K.P., Spragg, R., Gadek, J.E., Hyers, T.M., Longmore, W.J., Moxley, M.A., Cai, G.Z., Hite, R.D., Smith, R.M., Hudson, L.D., Crim, C., Newton, P., Mitchell, B.R., and Gold, A.J. (1997) Bovine surfactant therapy for patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 155, 1309–1315

    PubMed  CAS  Google Scholar 

  66. Pallua, N., Warbanow, K., Noah, E.M., Machens, H.G., Poets, C., Bernhard, W., and Berger, A. (1998) Intrabronchial surfactant application in cases of inhalation injury: first results from patients with severe burns and ARDS. Burns 24, 197–206

    Article  PubMed  CAS  Google Scholar 

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  1. Division of Pulmonary Biology, Children’s Hospital Medical Center and Children’s Hospital Research Foundation, Cincinnati, OH, USA

    Liqian Zhang & Jeffrey A. Whitsett

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  1. Liqian Zhang
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  1. Division of Critical Care Medicine, Children’s Hospital Medical Center and Children’s Hospital Research Foundation, Cincinnati, Ohio, USA

    Hector R. Wong  & Thomas P. Shanley  & 

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Zhang, L., Whitsett, J.A. (2001). Molecular Basis for Surfactant Function in ARDS. In: Wong, H.R., Shanley, T.P. (eds) Molecular Biology of Acute Lung Injury. Molecular and Cellular Biology of Critical Care Medicine, vol 1. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1427-5_12

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  • DOI: https://doi.org/10.1007/978-1-4615-1427-5_12

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