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The surfactant system of the adult lung: physiology and clinical perspectives

The clinical investigator volume 70, pages 637–657 (1992)Cite this article

Summary

Pulmonary surfactant is synthesized and secreted by alveolar type II cells and constitutes an important component of the alveolar lining fluid. It comprises a unique mixture of phospholipids and surfactant-specific proteins. More than 30 years after its first biochemical characterization, knowledge of the composition and functions of the surfactant complex has grown considerably. Its classically known role is to decrease surface tension in alveolar air spaces to a degree that facilitates adequate ventilation of the peripheral lung. More recently, other important surfactant functions have come into view. Probably most notable among these, surfactant has been demonstrated to enhance local pulmonary defense mechanisms and to modulate immune responses in the alveolar milieu. These findings have prompted interest in the role and the possible alterations of the surfactant system in a variety of lung diseases and in environmental impacts on the lung. However, only a limited number of studies investigating surfactant changes in human lung disease have hitherto been published. Preliminary results suggest that surfactant analyses, e.g., from bronchoalveolar lavage fluids, may reveal quantitative and qualitative abnormalities of the surfactant system in human lung disorders. It is hypothesized that in the future, surfactant studies may become one of our clinical tools to evaluate the activity and severity of peripheral lung diseases. In certain disorders they may also gain diagnostic significance. Further clinical studies will be necessary to investigate the potential therapeutic benefits of surfactant substitution and the usefulness of pharmacologic manipulation of the secretory activity of alveolar type II cells in pulmonary medicine.

Abbreviations

PC:

phospatidyleholine

DPPC:

dipalmitoylphosphatidylcholine

PG:

phosphatidylglycerol

PI:

phosphatidylinositol

SP-A, SP-B SP-C, SP-D:

surfactant-specific proteins A, B, C, and D

ARDS:

adult respiratory distress syndrome

IRDS:

infant respiratory distress syndrome

BAL:

bronchoalveolar lavage

IPF:

idiopathic pulmonary fibrosis

HP:

hypersensitivity pneumonitis

DIPD:

drug-induced pulmonary disease

References

  1. Armbruster S, Klein J, Stouten EM, Erdmann W, Lachmann B (1987) Surfactant in pulmonary oxygen toxicity. Adv Exp Med Biol 215:345–349

    Google Scholar 

  2. Arner EC, Rhoades RA (1973) Long-term nitrogen dioxide exposure. Arch Environ Health 26:156–160

    Google Scholar 

  3. Auten RL, Watkins RH, Shapiro DL, Horowitz S (1990) Surfactant apoprotein A (SP-A) is synthesized in airway cells. Am J Respir Cell Mol Biol 3:491–496

    Google Scholar 

  4. Avery ME, Mead J (1959) Surface properties in relation to atelectasis and hyaline membrane disease. Am J Dis Child 97:517–523

    Google Scholar 

  5. Baatz JE, Elledge B, Whitsett JA (1990) Surfactant protein SP-B induces ordering at the surface of model membrane bilayers. Biochemistry 29:6714–6720

    Google Scholar 

  6. Balis JU, Paterson JF, Lundh JM, Haller EM, Shelley S, Montgomery MR (1991) Ozone stress initiates acute perturbations of secreted surfactant membranes. Am J Pathol 138:847–857

    Google Scholar 

  7. Ballard PL (1989) Hormonal regulation of pulmonary surfactant. Endocr Rev 10:165–181

    Google Scholar 

  8. Barrow RE (1990) Chemical structure of phospholipids in the lungs and airways of sheep. Respir Physiol 79:1–8

    Google Scholar 

  9. Barrow RE, Hills BA (1979) Surface tension induced by dipalmitoyl lecithin in vitro under physiological conditions. J Physiol 297:217–227

    Google Scholar 

  10. Baughman RP, Strohofer S (1989) Lung derived surface active material (SAM) inhibits natural killer cell tumor cytotoxicity. J Clin Lab Immunol 28:51–54

    Google Scholar 

  11. Baughman RP, Stein E, MacGee J, Rashkin M, Sahebjami H (1984) Changes in fatty acids in phospholipids of the bronchoalveolar fluid in bacterial pneumonia and in adult respiratory distress syndrome. Clin Chem 30:521–523

    Google Scholar 

  12. Baughman RP, Strohofer S, Dohn M (1985) Decreased phosphatidylcholine in the lung fluid of patients with sarcoidosis. Lipids 20:496–499

    Google Scholar 

  13. Baughman RP, Mangels DJ, Strohofer S, Corser BC (1987) Enhancement of macrophage and monocyte cytotoxicity by the surface active material of lung lining fluid. J Lab Clin Med 109:692–697

    Google Scholar 

  14. Blank ML, Dalbey W, Nettesheim P, Price J, Creasia D, Snyder F (1978) Sequential changes in phospholipid composition and synthesis in lungs exposed to nitrogen dioxide. Am Rev Respir Dis 117:273–280

    Google Scholar 

  15. Bleasdale JE, Snyder JM, Johnson RL (1986) Structure and function of phosphatidylglycerol-deficient lung surfactant. Lung 164:339–353

    Google Scholar 

  16. Boudreau J, Vincent R, Nadeau D, Trottier B, Fournier M, Krzystyniak K, Chevalier G (1988) Toxicity of inhaled cadmium chloride: early responses of the antioxidant and surfactant systems in rat lungs. J Toxicol Environ Health 23:241–256

    Google Scholar 

  17. Catanzaro A, Richman P, Batcher S, Hallman M (1988) Immunomodulation by pulmonary surfactant. J Lab Clin Med 112:727–734

    Google Scholar 

  18. Chander A, Fisher AB (1990) Regulation of lung surfactant secretion. Am J Physiol (Lung Cell Mol Physiol 2) 258:L241-L253

    Google Scholar 

  19. Chida S, Phelps DS, Soll RF, Taeusch HW (1991) Surfactant proteins and anti-surfactant antibodies in sera from infants with respiratory distress syndrome with and without surfactant treatment. Pediatrics 88:84–89

    Google Scholar 

  20. Clements JA (1957) Surface tension of lung extracts. Proc Soc Exp Biol Med 95:170–172

    Google Scholar 

  21. Clements JA (1972) Smoking and pulmonary surfactant. N Engl J Med 286:261–262

    Google Scholar 

  22. Clements JA, Hustead RF, Johnson RP, Gibretz I (1961) Pulmonary surface tension and alveolar stability. J Appl Physiol 16:444–450

    Google Scholar 

  23. Cochrane CG, Revak SD (1991) Pulmonary surfactant protein B (SP-B): structure-function relationships. Science 254:566–568

    Google Scholar 

  24. Coonrod JD (1987) Role of surfactant free fatty acids in antimicrobial defenses. Eur J Respir Dis 71:209–214

    Google Scholar 

  25. Cooper JA,White DA, Matthay RA (1986) Drug-induced pulmonary disease. Part 1: cytotoxic drugs. Am Rev Respir Dis 133:321–340

    Google Scholar 

  26. Cooper JA, White DA, Matthay RA (1986) Drug-induced pulmonary disease. Part 2: noncytotoxic drugs. Am Rev Respir Dis 133:488–505

    Google Scholar 

  27. Corbet A, Bucciarelli R, Goldman S, Mammel M, Wold D, Long W (1991) Decreased mortality rate among small premature infants treated at birth with a single dose of synthetic surfactant: a multicenter controlled trial. J Pediatr 118:277–284

    Google Scholar 

  28. Coulombe PA, Bendayan M (1989) Lung surfactant associated proteins and type IV collagen share common epitopes. Am Rev Respir Dis 140:1040–1044

    Google Scholar 

  29. Crouch E, Persson A, Chang D, Parghi D (1991) Surfactant protein D. Increased accumulation in silica-induced pulmonary lipoproteinosis. Am J Pathol 139:765–776

    Google Scholar 

  30. De Lucca AJ, Brogden KA, Catalano EA, Morris NM (1991) Biophysical alteration of lung surfactant by extracts of cotton dust. Br J Ind Med 48:41–47

    Google Scholar 

  31. Dethloff LA, Gilmore LB, Gladen BC, George G, Chhabra RS, Hook GER (1986) Effects of silica on the composition of the pulmonary extracellular lining. Toxicol Appl Pharmacol 84:66–83

    Google Scholar 

  32. Disse BG (1987) The pharmacology of ambroxol — review and new results. Ear J Respir Dis 71 [Suppl 153]:255–262

    Google Scholar 

  33. Dobbs LG (1989) Pulmonary surfactant. Ann Rev Med 40:431–436

    Google Scholar 

  34. Dobbs LG, Wright JR, Gonzales R, Venstrom K, Nellenbogen J (1987) Pulmonary surfactant and its components inhibit secretion of phosphatidylcholine from cultured rat alveolar type II cells. Proc Natl Acad Sci USA 84:1010–1014

    Google Scholar 

  35. Edelson JD, Vadas P, Villar J, Mullen JBM, Pruzanski W (1991) Acute lung injury induced by phospholipase A2. Am Rev Respir Dis 143:1102–1109

    Google Scholar 

  36. Enhorning G (1989) Surfactant replacement in adult respiratory distress syndrome. Am Rev Respir Dis 140:281–283

    Google Scholar 

  37. Eskelson CD, Chvapil M, Kenneth A (1987) Pulmonary phospholipidosis in rats respiring air containing diesel particulates. Environ Res 44:260–271

    Google Scholar 

  38. Fasske E (1986) Pathogenesis of pulmonary fibrosis induced by chrysotile asbestos. Virchows Arch [A] 408:329–346

    Google Scholar 

  39. Fasske E, Morgenroth K (1983) Experimental bleomycin lung in mice. Lung 161:133–146

    Google Scholar 

  40. Finkelstein JN (1990) Physiologic and toxicologic responses of alveolar type II cells. Toxicology 60:41–52

    Google Scholar 

  41. Finley TN, Ladman AJ (1972) Low yield of pulmonary surfactant in cigarette smokers. N Engl J Med 285:223–227

    Google Scholar 

  42. Fisher JH, Park SS, Stelzner T, Shannon JM, Hofmann T (1991) In vivo regulation of surfactant proteins by glucocorticoids. Am J Respir Cell Mol Biol 5:63–70

    Google Scholar 

  43. Flores J (1990) Sixty years of surfactant research. Am J Physiol (Lung Cell Tvlol Physiol) 2:L238-L240

    Google Scholar 

  44. Floros J, Steinbrink R, Jacobs K, Phelps D, Kriz R, Reeny M, Sultzman L, Jones S, Taeusch HW, Frank HA, Fritsch EF (1986) Isolation and characterization of cDNA clones for the 35-kDa pulmonary surfactant-associated protein. J Biol Chem 261:9029–9033

    Google Scholar 

  45. Fowler AA, Hamman RF, Zerbe GO, Benson KN, Hyers TM (1985) Adult respiratory distress syndrome-prognosis after onset. Am Rev Respir Dis 132:472–478

    Google Scholar 

  46. Fuchimukai T, Fujiwara T, Takahashi A, Enhorning G (1987) Artificial pulmonary surfactant inhibited by proteins. J Appl Physiol 62:429–437

    Google Scholar 

  47. Fujiwara T, Konishi M, Chida S, Okuyama K, Ogawa Y, Takeuchi Y, Nishida H, Kito H, Fujimura M, Nakamura H, Hashimoto T (1990) Surfactant replacement therapy with a single postventilatory dose of a reconstituted bovine surfactant in preterm neonates with respiratory distress syndrome: final analysis of a multicenter, double-blind, randomized trial and comparison with similar trials. Pediatrics 86:753–764

    Google Scholar 

  48. Furlong ST, Raghuram G, Catalano PJ, Rose RM (1992) Lipid content of alveolar lining material collected by bronchoalveolar lavage. Am Rev Respir Dis 145:383–387

    Google Scholar 

  49. Gitlin JD, Soll RF, Parad RB, Horbar JD, Feldman HA, Lucey JF, Taeusch HW (1987) Randomized controlled trial of exogenous surfactant for the treatment of hyaline membrane disease. Pediatrics 79:31–37

    Google Scholar 

  50. Goldstein G, Luce JM (1990) Pharmacological treatment of the adult respiratory distress syndrome. Clin Chest Med 11:773–787

    Google Scholar 

  51. Gortner L, Bernsau U, Hellwege HH, Hieronimi G, Jorch G, Reiter HL (1990) A multicenter randomized controlled clinical trial of bovine surfactant for prevention of respiratory distress syndrome. Lung 168 [Suppl]:864–869

    Google Scholar 

  52. Grant MM, Brain JD, Vinegar A (1981) Pulmonary defense mechanisms in boa constrictor. J Appl Physiol (Respirat Environ Exercise Physiol) 50:979–983

    Google Scholar 

  53. Green FHY, Schürch S, De Sanctis GT, Wallace JA, Cheng S, Prior M (1991) Effects of hydrogen sulfide exposure on surface properties of lung surfactant. J Appl Physiol 70:1943–1949

    Google Scholar 

  54. Guzman J, Wang YM, Kalycioglu O, Schoenfeld B, Hamm H, Bartsch W, Costabel U (1992) Increased surfactant protein A (SP-A) content in human alveolar macrophages in hypersensitivity pneumonitis. Acta Cytol (in press)

  55. Haagsman H, Van Golde LMG (1985) Lung surfactant and pulmonary toxicology. Lung 163:275–303

    Google Scholar 

  56. Haagsman HP, Van Golde LMG (1991) Synthesis and assembly of lung surfactant. Annu Rev Physiol 53:441–464

    Google Scholar 

  57. Haagsman HP, Schuurmans E, Alink GM, Batenburg JJ, Van Golde LMG (1985) Effects of ozone on phospholipid synthesis by alveolar type II cells isolated from adult rat lung. Exp Lung Res 9:67–84

    Google Scholar 

  58. Halliday HL (1989) Clinical experience with exogenous natural surfactant. Dev Pharmacol Ther 13:173–181

    Google Scholar 

  59. Hallman M, Feldman BH, Kirkpatrick E, Gluck L (1977) Absence of phosphatidylglycerol (PG) in respiratory distress syndrome in the newborn. Pediatr Res 11:714–720

    Google Scholar 

  60. Hallman M, Epstein BL, Gluck L (1981) Analysis of labeling and clearance of lung surfactant phospholipids in rabbit. J Clin Invest 68:742–751

    Google Scholar 

  61. Hallman M, Spragg R, Harrell JH, Moser KM, Gluck L (1982) Evidence of lung surfactant abnormality in respiratory failure. J Clin Invest 70:673–683

    Google Scholar 

  62. Hallman M, Maasilta P, Kivisaari L, Mattson K (1990) Changes in surfactant in bronchoalveolar lavage fluid after hemithorax irradiation in patients with mesothelioma. Am Rev Respir Dis 141:998–1005

    Google Scholar 

  63. Hamm H, Lührs J, Kühne A, Guzman J, Costabel U, Bartsch W, Fabel H (1992) Surfactant protein A in bronchoalveolar lavage of sarcoidosis and hypersensitivity pneumonitis. Am Rev Respir Dis 145:A877

    Google Scholar 

  64. Hanahan DJ, Nelson DR (1984) Phospholipids as dynamic participants in biological processes. J Lipid Res 25:1528–1535

    Google Scholar 

  65. Harwood JL (1987) Lung surfactant. Prog Lipid Res 26:211–256

    Google Scholar 

  66. Hass MA, Longmore WJ (1979) Surfactant cholesterol metabolism of the isolated perfused rat lung. Biochim Biophys Acta 573:166–174

    Google Scholar 

  67. Hawgood S (1989) Pulmonary surfactant apoproteins: a review of protein and genomic structure. Am J Physiol 257:L13-L22

    Google Scholar 

  68. Higenbottam T (1989) Lung lipids and disease. Respiration 55 [Suppl 1]:14–27

    Google Scholar 

  69. Hildebrandt JN, Goerke J, Clements JA (1979) Pulmonary surface film stability and composition. J Appl Physiol 47:604–611

    Google Scholar 

  70. Hills BA (1990) The role of lung surfactant. Br J Anaesth 65:13–29

    Google Scholar 

  71. Holm BA, Matalon S (1989) Role of pulmonary surfactant in the development and treatment of adult respiratory distress syndrome. Anesth Analg 69:805–818

    Google Scholar 

  72. Holm BA, Notter RH (1987) Effects of hemoglobin and cell membrane lipids on pulmonary surfactant activity. J Appl Physiol 63:1434–1442

    Google Scholar 

  73. Holm BA, Notter RH, Finkelstein JN (1985) Surface property changes from interactions of albumin with natural surfactant and extracted lung lipids. Chem Phys Lipids 38:287–298

    Google Scholar 

  74. Holm BA, Matalon S, Finkelstein JN, Notter RH (1988) Type II pneumocyte changes during hyperoxic lung injury and recovery. J Appl Physiol 65:2672–2678

    Google Scholar 

  75. Holt PG (1986) Down-regulation of immune responses in the lower respiratory tract: the role of alveolar macrophages. Clin Exp Immunol 63:261–270

    Google Scholar 

  76. Honda Y, Tsunematsu K, Suzuki A, Akino T (1988) Changes in phospholipids in bronchoalveolar lavage fluid of patients with interstitial lung diseases. Lung 166:209–301

    Google Scholar 

  77. Honda Y, Kataoka K, Hayashi H, Takahashi H, Suzuki A, Akino T (1989) Alterations of acidic phospholipids in bronchoalveolar lavage fluids of patients with pulmonary alveolar proteinosis. Clin Chim Acta 181:11–18

    Google Scholar 

  78. Hook GER, Gilmore LB, Talley FA (1986) Dissolution and reassembly of tubular myelin-like multilamellated structures from the lungs of patients with pulmonary alveolar proteinosis. Lab Invest 55:194–208

    Google Scholar 

  79. Horbar JD, et al. (1989) A multicenter, randomized, placebo-controlled trial of surfactant therapy for respiratory distress syndrome. N Engl J Med 320:959–965

    Google Scholar 

  80. Horiuchi T, Mason RJ, Kuroki Y, Cherniack RM (1990) Surface and tissue forces, surfactant protein A, and the phospholipid components of pulmonary surfactant in bleomycin-induced pulmonary fibrosis in the rat. Am Rev Respir Dis 141:1006–1013

    Google Scholar 

  81. Hughes DA, Haslam PL (1989) Changes in phosphatidylglycerol in bronchoalveolar lavage fluids from patients with cryptogenic fibrosing alveolitis. Chest 95:82–89

    Google Scholar 

  82. Idegami K, Mori K, Misumi A, Akagi M (1983) Changes of alveolar stability and phospholipids in pulmonary surfactant in acute pancreatitis. Jpn J Surg 13:227–235

    Google Scholar 

  83. Jobe A, Ikegami M (1987) Surfactant for the treatment of respiratory distress syndrome. Am Rev Respir Dis 136:1256–1275

    Google Scholar 

  84. Johannson J, Curstedt T, Jörnvall H (1991) Surfactant protein B: disulfide bridges, structural properties, and kringle similarities. Biochem 30:6917–6921

    Google Scholar 

  85. Joka T, Obertacke U (1989) Neue medikamentöse Behandlung im ARDS: Effekt einer intrabronchialen xenogenen Surfactantapplikation. Z Herz Thorax Gefäßchir 3 [Suppl 1]:21–24

    Google Scholar 

  86. Jonsson S, Musher DM, Goree A, Lawrence EC (1986) Human alveolar lining material and antibacterial defenses. Am Rev Respir Dis 133:136–140

    Google Scholar 

  87. Joshi UM, Kodavanti RS, Coudert B, Dwyer TM, Mehendale HM (1988) Types of interaction of amphiphilic drugs with phospholipid vesicles. J Pharmacol Exp Ther 246:150–157

    Google Scholar 

  88. Juers JA, Rogers RM, McCurdy JB, Cook WW (1976) Enhancement of bactericidal capacity of alveolar macrophages by human alveolar lining material. J Clin Invest 58:271–275

    Google Scholar 

  89. Jurmann JM, Obladen M, Schaefers HJ, Dammenhayn L, Haverich A (1989) Analysis of Bronchoalveolar lavage and pulmonary alveolar surfactant for diagnosis of rejection and infection in heart-lung transplantation. Transplant Proc 21:2581–2582

    Google Scholar 

  90. Kawada H, Horiuchi T, Shannon JM, Kuroki Y, Voelker DR, Mason RJ (1989) Alveolar type 11 cells, surfactant protein A (SP-A), and the phospholipid components of surfactant in acute silicosis in the rat. Am Rev Respir Dis 140:460–470

    Google Scholar 

  91. Kawanami O, Ferrans VJ, Crystal RG (1982) Structure of alveolar epithelial cells in patients with fibrotic lung disorders. Lab Invest 46:39–53

    Google Scholar 

  92. Kelly CA, Fenwick JD, Corris PA, Fleetwood A, Hendrick DJ, Walters EH (1988) Fluid dynamics during bronchoalveolar lavage. Am Rev Respir Dis 138:81–84

    Google Scholar 

  93. Kim KC, Opaskar-Hincman H, Bhaskar KR (1989) Secretions from primary hamster tracheal surface epithelial cells in culture: mucin-like glycoproteins, proteoglycans, and lipids. Exp Lung Res 15:299–314

    Google Scholar 

  94. King RJ, Klass DJ, Gikas EG, Clements JA (1973) Isolation of apoproteins from canine surface active material. Am J Physiol 224:788–795

    Google Scholar 

  95. King RJ, Coalson JJ, Seidenfeld JJ, Anzueto AR, Smith DB, Peters JI (1989) O2- and pneumonia-induced lung injury. II. Properties of pulmonary surfactant. J Appl Physiol 67:357–365

    Google Scholar 

  96. Klepetko W, Lohninger A, Wisser W, Mueller MR, Khunl-Brady G, Windisch A, Eckersberger F, Wolner E (1990) Pulmonary surfactant in Bronchoalveolar lavage after canine lung transplantation. J Thorac Cardiovasc Surg 99:1048–1058

    Google Scholar 

  97. Kobayashi T, Nitta K, Ganzuka M, Inui S, Grossmann G, Robertson B (1991) Inactivation of exogenous surfactant by pulmonary edema fluid. Pediatr Res 29:353–356

    Google Scholar 

  98. Kuroki Y, Shiratori M, Murata Y, Akino T (1991) Surfactant protein D (SP-D) counteracts the inhibitory effect of surfactant protein A (SP-A) on phospholipid secretion by alveolar type II cells. Biochem J 279:115–119

    Google Scholar 

  99. Kuroki Y, Shiratori M, Ogaswara Y, Tsuzuki A, Akino T (1991) Characterization of pulmonary surfactant protein D: its copurification with lipids. Biochim Biophys Acta 1086:185–190

    Google Scholar 

  100. Lachman B (1989) Animal models and clinical pilot studies of surfactant replacement in adult respiratory distress syndrome. Eur Respir J 2 [Supp13] :98s–103s

  101. Lamm WJE, Albert RK (1990) Surfactant replacement improves lung recoil in rabbit lungs after acid aspiration. Am Rev Respir Dis 142:1279–1283

    Google Scholar 

  102. Le Mesurier SM, Stewart BW, Lykke AWJ (1981) Injury to type II pneumocytes in rats exposed to cigarette smoke. Environ Res 24:207–217

    Google Scholar 

  103. Li JJ, Sanders RL, McAdam KP, Geland JA, Burke JF (1989) Endotoxin suppresses surfactant synthesis in cultured rat lung cells. J Trauma 29:180–188

    Google Scholar 

  104. Liau DF, Barrett CR, Bell ALL, Ryan SF (1987) Functional abnormalities of lung surfactant in experimental acute alveolar injury in the dog. Am Rev Respir Dis 136:395–401

    Google Scholar 

  105. Liley HG, White RT, Benson BJ, Ballard PL (1988) Glucocorticoids both stimulate and inhibit production of pulmonary surfactant protein A in fetal human lung. Proc Natl Acad Sci USA 85:9096–9100

    Google Scholar 

  106. Long W, Corbet A, Cotton R, Courtney S, McGuiness G, Walter D, Watts J, Smyth J, Bard H, Chernick V (1991) A controlled clinical trial of synthetic surfactant in infants weighing 1250 g or more with respiratory distress syndrome. N Engl J Med 325:1696–1703

    Google Scholar 

  107. Low RB (1989) Bronchoalveolar lavage lipids in idiopathic pulmonary fibrosis. Chest 95:3–5

    Google Scholar 

  108. Low RB, Davis GS, Giancola MS (1978) Biochemical analyses of Bronchoalveolar lavage fluids of healthy human volunteer smokers and nonsmokers. Am Rev Respir Dis 118:863–875

    Google Scholar 

  109. Malhotra R, Thiel S, Reid KBM, Sim RB (1990) Human leucocyte Clq receptor binds other soluble proteins with collagen domains. J Exp Med 172:955–959

    Google Scholar 

  110. Manz-Keinke H, Egenhofer C, Plattner H, Schlepper-Schäfer J (1991) Specific interaction of lung surfactant protein A (SP-A) with rat alveolar macrophages. Exp Cell Res 192:597–603

    Google Scholar 

  111. Marcy TW, Merrill WW, Rankin JA, Reynolds HY (1987) Limitations of using urea to quantify epithelial lining fluid recovered by bronchalveolar lavage. Am Rev Respir Dis 135:1276–1280

    Google Scholar 

  112. Mason RJ (1987) Surfactant in adult respiratory distress syndrome. Eur J Respir Dis 71 [Suppl 153]:229–236

    Google Scholar 

  113. Masuda T, Shimura S, Sasaki H, Takishima T (1991) Surfactant apoprotein-A concentration in sputum for diagnosis of pulmonary alveolar proteinosis. Lancet 337:580–582

    Google Scholar 

  114. Matalon S, Holm BA, Loewen GM, Baker RR, Notter RH (1988) Sublethal hyperoxic injury to the alveolar epithelium and the pulmonary surfactant system. Exp Lung Res 14:1021–1033

    Google Scholar 

  115. Matalon S, Holm BA, Baker RR, Whitfield MK, Freeman BA (1990) Characterization of antioxidant activities of pulmonary surfactant mixtures. Biochim Biophys Acta 1035:121–127

    Google Scholar 

  116. McCormack FX, King TE, Voelker DR, Robinson PC, Mason RJ (1991) Idiopathic pulmonary fibrosis. Abnormalities in the Bronchoalveolar lavage content of surfactant protein A. Am Rev Respir Dis 144:160–166

    Google Scholar 

  117. Merritt TA, Strayer DS, Hallman M, Spragg RD, Wozniak P (1988) Immunologic consequences of exogenous surfactant administration. Semin Perinatol 12:221–230

    Google Scholar 

  118. Miles PR, Ma JYC, Bowman L (1988) Degradation of pulmonary surfactant disaturated phosphatidylcholines by alveolar macrophages. J Appl Physiol 64:2474–2481

    Google Scholar 

  119. Miller BE, Hook GER (1990) Hypertrophy and hyperplasia of alveolar type II cells in response to silica and other pulmonary toxicants. Environ Health Perspect 85:15–23

    Google Scholar 

  120. Miller K, Cottrell RC (1987) Adverse effects of toxins and drugs on the surfactant systems. Eur J Respir Dis 71 [Suppl 153]:237–241

    Google Scholar 

  121. Montgomery AB, Stager MA, Carrico CJ, Hudson LD (1985) Causes of mortality in patients with the adult respiratory distress syndrome. Am Rev Respir Dis 132:485–489

    Google Scholar 

  122. Morgenroth K (1986) Das Surfactantsystem der Lunge. de Gruyter, Berlin, New York

    Google Scholar 

  123. Morrow PE (1984) Toxicological data on NOx: an overview. J Toxicol Environ Health 13:205–227

    Google Scholar 

  124. Morton NS (1989) Pulmonary surfactant: physiology, pharmacology and clinical uses. B J Hosp Med 42:52–58

    Google Scholar 

  125. Morton NS (1990) Exogenous surfactant treatment for the adult respiratory distress syndrome? A historical perspective. Thorax 45:825–830

    Google Scholar 

  126. Nogee LM, Wispe JR (1988) Effects of pulmonary oxygen injury on airway content of surfactant-associated protein A. Pediatr Res 24:568–573

    Google Scholar 

  127. Nosaka S, Sakai T, Yonekura M, Yoshikawa K (1990) Surfactant for adults with respiratory failure. Lancet 336:947–948

    Google Scholar 

  128. Novick RJ, Possmayer F, Veldhuizen RAW, Menkis AH, McKenzie FN (1991) Surfactant analysis and replacement therapy: a future tool of the lung transplant surgeon? Ann Thorac Surg 52:1194–1200

    Google Scholar 

  129. Oetomo SB, Lewis J, Ikegami M, Jobe AH (1990) Surfactant treatments alter endogenous surfactant metabolism in rabbit lungs. J Appl Physiol 68:1590–1596

    Google Scholar 

  130. Oldham KT, Guice KS, Stetson PS, Wolfe RR (1989) Bacteremia-induced suppression of alveolar surfactant production. J Surg Res 47:397–402

    Google Scholar 

  131. O'Neill S, Lesperance E, Klass DJ (1984) Rat lung lavage surfactant enhances bacterial phagocytosis and intracellular killing by alveolar macrophages. Am Rev Respir Dis 130:225–230

    Google Scholar 

  132. Oosting RS, Van Greevenbroek MMJ, Verhoef J, Van Golde LMG, Haagsman HP (1991) Structural and functional changes of surfactant protein A induced by ozone. Am J Physiol 261 (Lung Cell Mot Physiol 5):L77-L83

    Google Scholar 

  133. Osanai K, Takahashi K, Sato S, Iwabuchi K, Ohtake K, Sata M, Yasui S (1991) Changes of lung surfactant and pressure-volume curve in bleomycin-induced pulmonary fibrosis. J Appl Physiol 70:1300–1308

    Google Scholar 

  134. Oulton M, Moores HK, Scott JE, Janigan DT, Hajela R (1991) Effects of smoke inhalation on surfactant phospholipids and phospholipase A2 activity in the mouse lung. Am J Pathol 138:195–202

    Google Scholar 

  135. Pattle RE (1955) Properties, function and origin of the alveolar lining layer. Nature 175:1125–1126

    Google Scholar 

  136. Pattle RE (1977) The relation between surface tension and area in the alveolar lining film. J Physiol (Lond) 269:591–604

    Google Scholar 

  137. Persson A, Chang D, Rust K, Moxley M, Longmore W, Crouch E (1989) Purification and biochemical characterization of CP4 (SP-D), a collagenous surfactant-associated protein. Biochemistry 28:6361–6367

    Google Scholar 

  138. Persson A, Chang D, Crouch E (1990) Surfactant protein D is a divalent cation-dependent carbohydrate-binding protein. J Biol Chem 265:5755–5760

    Google Scholar 

  139. Pettenazzo A, Ikegami M, Seidner S, Jobe A (1988) Clearance of surfactant phosphatidylcholine from adult rabbit lungs. J Appl Physiol 64:120–127

    Google Scholar 

  140. Pettenazzo A, Jobe A, Humme J, Seidner S, Ikegami M (1988) Clearance of surfactant phosphatidylcholine via the upper airways in rabbits. J Appl Physiol 65:2151–2155

    Google Scholar 

  141. Phelps DS, Floros J (1988) Localization of surfactant protein synthesis in human lung by in situ hybridization. Am Rev Respir Dis 137:939–942

    Google Scholar 

  142. Phelps DS, Rose RM (1991) Increased recovery of surfactant protein A in AIDS-related pneumonia. Am Rev Respir Dis 143:1072–1075

    Google Scholar 

  143. Pison U, Seeger W, Buchhorn R, Joka T, Brand M, Obertacke U, Neuhof H, Schmit-Neuerburg K (1989) Surfactant abnormalities in patients with respiratory failure after multiple trauma. Am Rev Respir Dis 140:1033–1039

    Google Scholar 

  144. Pison U, Obertacke U, Brand M, Seeger W, Joka T, Bruch J, Schmit-Neuerburg KP (1990) Altered pulmonary surfactant in uncomplicated and septicemia-complicated courses of acute respiratory failure. J Trauma 30:19–26

    Google Scholar 

  145. Possmayer F (1988) A proposed nomenclature for pulmonary surfactant-associated proteins. Am Rev Respir Dis 138:990–998

    Google Scholar 

  146. Possmayer F (1990) The role of surfactant-associated proteins. Am Rev Respir Dis 142:749–752

    Google Scholar 

  147. Prevost MC, Soula G, Douste-Blazy L (1979) Biochemical modification of pulmonary surfactant after bromhexine derivate injection. Respiration 37:215–219

    Google Scholar 

  148. Puchelle E, Jacquot J, Beck G, Zahm JM, Galabert C (1985) Rheological and transport properties of airway secretions in cystic fibrosis — relationships with the degree of infection and severity of the disease. Eur J Clin Invest 15:389–394

    Google Scholar 

  149. Rao GA, Larkin EC, Harkema JR, Dungworth DL (1985) Changes in lipids of lung lavage in monkeys after chronic exposure to ambient levels of ozone. Toxicol Lett 29:207–209

    Google Scholar 

  150. Reynolds HY (1991) Immunologic system in the respiratory tract. Physiol Rev 71:1117–1133

    Google Scholar 

  151. Rich EA (1990) Pulmonary surfactant as a physiologic immunosuppressive agent. J Lab Clin Med 116:4–5

    Google Scholar 

  152. Richman PS, Spragg RG, Robertson B, Merritt TA, Curstedt T (1989) The adult respiratory distress syndrome: first trials with surfactant replacement. Eur Respir J 2 [Suppl 3]:109s–111s

  153. Richman PS, Batcher S, Catanzaro A (1990) Pulmonary surfactant suppresses the immune lung injury response to inhaled antigen in guinea pigs. J Lab Clin Med 116:18–26

    Google Scholar 

  154. Robinson PC, Watters LC, King TE, Mason RJ (1988) Idiopathic pulmonary fibrosis — abnormalities in bronchoalveolar lavage fluid. Am Rev Respir Dis 137:585–591

    Google Scholar 

  155. Rooney SA (1985) The surfactant of the lung. In: Witschi HP, Brain JD (eds) Toxicology of inhaled particles. pp 471–502

  156. Rossi GA, Balbi B, Benatti U, Morelli A, Sacco O, Vasallo F, Ravazzoni C (1987) Changes in pulmonary surfactant composition following MACC chemotherapy for lung carcinoma. Eur J Respir Dis 71:400–409

    Google Scholar 

  157. Ryan RM, Morris RE, Rice WR, Ciraolo G, Whitsett JA (1989) Binding and uptake of pulmonary surfactant protein (SP-A) by pulmonary type II epithelial cells. J Histochem Cytochem 37:429–440

    Google Scholar 

  158. Schäfer KP, Voss T, Melchers K, Eistetter H (1990) Lung surfactant: a biotechnological challenge. Lung 168 [Suppl]:851–859

    Google Scholar 

  159. Schwartz LW, Christman CA (1979) Alveolar macrophage migration — influence of lung lining material. Am Rev Respir Dis 120:429–439

    Google Scholar 

  160. Seeger W, Stohr G, Wolf HRD, Neuhof H (1985) Alteration of surfactant function due to protein leakage: special interaction with fibrin monomer. J Appl Physiol 58:326–338

    Google Scholar 

  161. Seeger W, Pison U, Buchhorn R, Obertacke U, Joka T (1990) Surfactant abnormalities and adult respiratory failure. Lung 168 [Suppl]:891–902

    Google Scholar 

  162. Sheehan PM, Stokes DC, Yeh YY, Hughes WT (1986) Surfactant phospholipids and lavage phospholipase A2 in experimental Pneumocystis carinii pneumonia. Am Rev Respir Dis 134:526–531

    Google Scholar 

  163. Shimura S, Maeda S, Takismima T (1984) Giant lamellar bodies in alveolar type II cells of rats exposed to a low concentration of ozone. Respiration 46:303–309

    Google Scholar 

  164. Sitrin RG, Ansfield MJ, Kaltreider HB (1985) The effect of pulmonary surface-active material on the generation and expression of murine B- and T-lymphocyte effector functions in vitro. Exp Lung Res 9:85–97

    Google Scholar 

  165. Slomiany A., Smith FB, Slomiany BL (1979) Isolation and characterization of a sulfated glyceroglucolipid from alveolar lavage of rabbit. Eur J Biochem 98:47–51

    Google Scholar 

  166. Speer CP, Harms K, Herting E, Neumann N, Curstedt T, Robertson B (1990) Early versus late surfactant replacement therapy in severe respiratory distress syndrome. Lung 168 [Suppl]:870–876

    Google Scholar 

  167. Strayer DS, Merritt TA, Hallman M (1989) Surfactant replacement: immunological considerations. Eur Respir J 2 [Suppl 3]:91s–96s

  168. Tahvanainen J, Hallman M (1987) Surfactant abnormality after endotoxin-induced lung injury in guinea pigs. Eur J Respir Dis 71:250–258

    Google Scholar 

  169. Takahashi A, Waring AJ, Amirkhanian J, Fan B, Taeusch HW (1990) Structure-function relationships of bovine pulmonary surfactant proteins SP-B and SP-C. Biochim Biophys Acta 1044:43–49

    Google Scholar 

  170. Ten Have-Opbroek AAW, Otto-Verberne CJM, Dubbeldam JA, Dykman JH (1991) The proximal border of the human respiratory unit, as shown by scanning and transmission electron microscopy and light microscopical cytochemistry. Anat Rec 229:339–354

    Google Scholar 

  171. Termer AJ, Robinson SL, Borchelt J, Wright JR (1989) Human pulmonary surfactant protein (SP-A), a protein structurally homologous to C1q, can enhance FcR- and CRI-mediated phagocytosis. J Biol Chem 264:13923–13928

    Google Scholar 

  172. Thakur NR, Tesan M, Tyler NE, Bleasdale JE (1986) Altered lipid synthesis in type 11 pneumocytes exposed to lung surfactant. Biochem J 240:679–690

    Google Scholar 

  173. Thrall RS, Swendsen CL, Shannon TH, Kennedy CA, Frederick DS, Grunze MF, Sulavik SB (1987) Correlation of changes in pulmonary surfactant phospholipids with compliance in bleomycin-induced pulmonary fibrosis in the rat. Am Rev Respir Dis 136:113–118

    Google Scholar 

  174. Van Golde LMG (1985) Synthesis of surfactant lipids in the adult and fetal lung: pathways and regulatory aspects. Eur J Respir Dis 142:19–24

    Google Scholar 

  175. Van Golde LMG, Batenburg JJ, Robertson B (1988) Metabolism of phospholipids in the lung. Physiol Rev 68:374–455

    Google Scholar 

  176. Van Golde LMG, Vries ACJ de, Batenburg JJ (1987) Aspects of metabolism and storage of pulmonary surfactant: experiments with isolated type II pneumocytes and lamellar bodies. Eur J Respir Dis 71 [Suppl 153]:182–188

    Google Scholar 

  177. Van Iwaarden F, Welmers B, Verhoef J, Haagsman HP, Van Golde LMG (1990) Pulmonary surfactant protein A enhances the host-defence mechanism of rat alveolar macrophages. Am J Respir Cell Mol Biol 2:91–98

    Google Scholar 

  178. Van Iwaarden JF, van Strijp JA, Ebskamp MJ, Welmers AC, Verhoef J, Van Golde LM (1991) Surfactant protein A is opsonin in phagocytosis of herpes simplex virus type 1 by rat alveolar macrophages. Am J Physiol 261: L204-L209

    Google Scholar 

  179. Venkitaraman AR, Hall SB, Whitsett JA, Notter RH (1990) Enhancement of biophysical activity of lung surfactant extracts and phospholipid-apoprotein mixtures by surfactant protein A. Chem Phys Lipids 56:185–194

    Google Scholar 

  180. Von Neergard K (1929) Neue Auffassungen über einen Grundbegriff der Atemmechanik. Z Ges Exp Med 66:373–393

    Google Scholar 

  181. Voorhout WF, Veenendaal T, Haatsman HP, Verkleij AJ, Van Golde LMG, Geuze HJ (1991) Surfactant protein A is localized at the corners of the pulmonary tubular myelin lattice. J Histochem Cytochem 39:1331–1336

    Google Scholar 

  182. Voss T, Eistetter H, Schdfer KP, Engel J (1988) Macromolecular organization of natural and recombinant lung surfactant protein SP 28–36. J Mol Biol 201:219–227

    Google Scholar 

  183. Voss T, Melchers K, Scheirle G, Schäfer KP (1991) Structural comparison of recombinant pulmonary surfactant protein SP-A derived from two human coding sequences: implications for the chain composition of natural human SP-A. Am J Repir Cell Mol Biol 4:88–94

    Google Scholar 

  184. Weaver TE (1991) Surfactant proteins and SP-D. Am J Respir Cell Mol Biol 5:4–5

    Google Scholar 

  185. Weaver TE, Whitsett JA (1991) Function and regulation of expression of pulmonary surfactant-associated proteins. Biochem J 273:249–264

    Google Scholar 

  186. Weaver TE, Sarin VK, Sawtell N, Hull WM, Whitsett JA (1988) Identification of surfactant proteolipid SP-B in human surfactant and fetal lung. J Appl Physiol 65:982–987

    Google Scholar 

  187. Welte T, Hamm H Fabel H (1991) Mesalazine alveolitis. Lancet 338:1273

    Google Scholar 

  188. White RT, Damm D, Miller J, Spratt K, Schilling J, Hawgood S, Benson B, Cordell B (1985) Isolation and characterization of the human pulmonary surfactant apoprotein gene. Nature 317:361–363

    Google Scholar 

  189. Whitsett JA, Ross G, Weaver T, Rice W, Dion C, Hull W (1985) Glycosylation and secretion of surfactant-associated glycoprotein A. J Biol Chem 260:15273–15279

    Google Scholar 

  190. Wichert Pv. (1985) Endobronchial surface active phospholipids: clinical conclusions. Eur J Respir Dis 142 [Suppl]:77–79

    Google Scholar 

  191. Williams MC, Hawgood S, Hamilton RL (1991) Changes in lipid structure produced by surfactant proteins SP-A, SP-B, and SP-C. Am J Respir Cell Mol Biol 5:41–50

    Google Scholar 

  192. Wilsher ML, Hughes DA, Haslam PL (1988) Immunoregulatory properties of pulmonary surfactant: effect of lung lining fluid on proliferation of human blood lymphocytes. Thorax 43:354–359

    Google Scholar 

  193. Wilsher ML, Parker DJ, Haslam PL (1990) Immunosuppression by pulmonary surfactant: mechanisms of action. Thorax 45:3–8

    Google Scholar 

  194. Wilson TA (1981) Relations among recoil pressure, surface area, and surface tension in the lung. J Appl Physiol 50:921–926

    Google Scholar 

  195. Wright ES (1986) Effects of short-term exposure to diesel exhaust on lung cell proliferation and phospholipid metabolism. Exp Lung Res 10: 39–55

    Google Scholar 

  196. Wright JR (1990) Clearance and recycling of pulmonary surfactant. Am J Physiol 259:L1-L12

    Google Scholar 

  197. Wright JR, Clements JA (1987) Metabolism and turnover of lung surfactant. Am Rev Respir Dis 135:426–444

    Google Scholar 

  198. Wright JR, Wager RE, Hawgood S, Dobbs LG, Clements JA (1987) Surfactant apoprotein Mr=26.000–36.000 enhances uptake of liposomes by type II cells. J Biol Chem 262:2888–2894

    Google Scholar 

  199. Yu SH, Possmayer F (1990) Role of bovine pulmonary-associated proteins in the surface active property of phospholipid mixtures. Biochim Biophys Acta 1046:233–241

    Google Scholar 

  200. Zelter M, Escudier BJ, Hoeffel JM, Murray JF (1990) Effects of aerosolized artificial surfactant on repeated oleic acid injury in sheep. Am Rev Respir Dis 141:1014–1019

    Google Scholar 

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  1. H. Hamm

    Present address: Abteilung Pneumologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-Strasse 8, W-3000, Hannover 61, Germany

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  1. Abteilung Pneumologie, Zentrum Innere Medizin und Dermatologie, Medizinische Hochschule Hannover, Germany

    H. Hamm & H. Fabel

  2. Fraunhofer Institut für Toxikologie und Aerosolforschung, Hannover

    W. Bartsch

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  2. H. Fabel
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Hamm, H., Fabel, H. & Bartsch, W. The surfactant system of the adult lung: physiology and clinical perspectives. Clin Investig 70, 637–657 (1992). https://doi.org/10.1007/BF00180279

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Key words

  • Pulmonary surfactant
  • Phospholipids
  • Surfactant proteins
  • Alveolar stability
  • Air pollution
  • Pulmonary defense
  • Adult respiratory distress syndrome
  • Surfactant therapy
  • Bronchoalveolar lavage