Mediators in Acute Lung Injury: The Whole Body Inflammatory Response Hypothesis

  • S. Westaby
Part of the Current Concepts in Critical Care book series (CRITICAL CARE)


A wide variety of extrapulmonary events such as major sepsis, burns, fat embolism, multiple trauma and pancreatitis may initiate an acute lung injury with the development of the adult respiratory distress syndrome (ARDS) (Anon. 1985). This same phenomenon, though usually in a much less severe form, has been observed in the controlled therapeutic situations of haemodialysis (Craddock et al. 1977), cardiopulmonary bypass (Westaby 1983) and nylon fibre leucapheresis (Nusbacher et al. 1978) where blood traverses a number of allegedly biocompatible foreign surfaces.


Cardiopulmonary Bypass Acute Lung Injury Chronic Granulomatous Disease Adult Respiratory Distress Syndrome Human Neutrophil Elastase 
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  1. Anonymous (1985) Adult respiratory distress syndrome. Lancet I:301–303.Google Scholar
  2. Asada S, Yamaguchi M (1971) Fine structural changes in the lung following cardiopulmonary bypass. Chest 59:478.PubMedCrossRefGoogle Scholar
  3. Brigham KL, Ogletree ML (1981) Effects of Prostaglandins and related compounds on lung vascular permeability. Bull Eur Physiopathol Respir 17:703–722.PubMedGoogle Scholar
  4. Chenoweth DE, Cooper SW, Hugli TE, Stewart R, Blackstone EH, Kirklin JW (1981) Complement activation during cardiopulmonary bypass: evidence for generation of C3a and C5a anaphylatoxins. N Engl J Med 304:497.PubMedCrossRefGoogle Scholar
  5. Craddock PR, Fehr J, Dalmasso AP, Brigham KL, Jacobs HS (1977) Haemodialysis leukopenia. Pulmonary vascular leukostasis resulting from complement activation by dialysis cellophane membrane. J Clin Invest 59:589.CrossRefGoogle Scholar
  6. Cochrane CG, Spragg RG, Davat SD, Cohen AB, McGuire WW (1984) The presence of neutrophil elastase and evidence of oxidant activity in broncho-alveolar lavage fluid of patients with adult respiratory distress syndrome. Am Rev Respir Dis [Suppl] 127:25–27.Google Scholar
  7. Gavasocchi NC, Pluth JR, Schaff HV, Orszulak TA, Homburger HA, Solis E, Kaye MP, Clancy MS, Kolff J, Deeb GM (1986) Complement activation during cardiopulmonary bypass: comparison of bubble and membrane oxygenators. J Thorac Cardiovasc Surg 91:252–258.Google Scholar
  8. Gnanaduoai TV, Branthwaite MA, Colbeck JF, Wellman E (1978) Lysosomal enzyme release from the lungs after cardiopulmonary bypass. Anaesthesia 33:227.CrossRefGoogle Scholar
  9. Harada RN, Bowman CM, Fox FB, Repire JE (1982) Alveolar macrophage secretions: initiators of inflammation in pulmonary oxygen toxicity. Chest 81:52–54.CrossRefGoogle Scholar
  10. Harada RV, Vatter AE, Repine JE (1983) Oxygen radical scavengers protect alveolar macrophages from hyperoxic injury in vitro. Am Rev Respir Dis 128:552–559.Google Scholar
  11. Henson RM (1972) Pathologic mechanisms in neutrophil-medicated injury. Am J Pathol 68:593–612.PubMedGoogle Scholar
  12. Hohn DC, Meyers AJ, Gherini ST, Beckman A, Markison RE, Churg AM (1980) Production of acute pulmonary injury by leukocytes and activated complement. Surgery 88:48.PubMedGoogle Scholar
  13. Johnson RB, Keele BB, Misoa HP (1975) The role of Superoxide anion generation in phagocytic bactericidal activity: studies with normal and chronic granulomatous disease leukocytes: J Clin Invest 55:1357–1372.CrossRefGoogle Scholar
  14. Kirklin JK, Westaby S, Blackstone EH, Kirklin JW, Chenoweth DE, Pacifico AD (1983) Complement and the damaging effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg 86:845.PubMedGoogle Scholar
  15. Larsen GL, McCarthy K, Webster RO, Henson JE, Henson PM (1980) A differential effect of C5a and C5a des arg in the induction of pulmonary inflammation. Am J Pathol 100:179–192.PubMedGoogle Scholar
  16. Luterman A, Manwaring D, Curreri PW (1977) The role of fibrinogen degradation products in the pathogenesis of the respiratory distress syndrome. Surgery 82:703–709.PubMedGoogle Scholar
  17. Martin WJ, Gadek JE, Hunninghake GW, Crystal RG (1981) Oxidant injury of lung parenchymal cells. J Clin Invest 68:1277–1288.PubMedCrossRefGoogle Scholar
  18. Nusbacher J, Rosenfeld SI, MacPherson JL, Theim PA, Leddy JP (1978) Nylon fibre leukophoresis: associated complement component changes and granulocytopenia. Blood 51:359.PubMedGoogle Scholar
  19. Ratliffe NB, Young WA, Hackel DB, Mikat E, Wilson JW (1973) Pulmonary injury secondary to extracorporeal circulation. J Thorac Cardiovasc Surg 65:425.Google Scholar
  20. Reynolds HY (1983) Lung inflammation: role of endogenous chemotactic factors in attracting polymorphonuclear granulocytes. Am Rev Respir Dis 127 [Suppl]:S16–S25.PubMedGoogle Scholar
  21. Royston D, Minty BD, Higgenbottam TW, Wallwork J, Jones GJ (1985) The effect of surgery with cardiopulmonary bypass on alveolar-capillary barrier function in human beings. Ann Thorac Surg 40:139–143.PubMedCrossRefGoogle Scholar
  22. Royston D, Fleming JS, Westaby S, Taylor KM (1986) Increased production of peroxidation products associated with open heart surgery: evidence for free radical generation. J Thorac Cardiovasc Surg (in press).Google Scholar
  23. Ruddy S, Gigli I, Austen KF (1972) The complement system of man. N Engl J Med 287:489–495.PubMedCrossRefGoogle Scholar
  24. Schlag G, Voigt WH, Redl H, Glatzl A (1980) Vergleichende Morphologie des posttraumatisches Lungenversagens. Anaesthesiol Intensivther Notfallmed 15:315–339.CrossRefGoogle Scholar
  25. Schraufstatter IU, Revak SD, Cochrane CG (1984) Proteases and oxidants in experimental pulmonary inflammatory injury. J Clin Invest 73:1175.PubMedCrossRefGoogle Scholar
  26. Shasby DM, Van Benthuysen KM, Tate RM, Shasby SS, McMustry IF, Repire JE (1982) Granulocytes mediate acute oedematous lung injury in rabbits and isolated rabbit lungs perfused with phorbolmyristate acetate: role of oxygen radicals. Am Rev Respir Dis 125:443–447.PubMedGoogle Scholar
  27. Tate RM, Repine JE (1983) Neutrophils and the adult respiratory distress syndrome. Am Rev Respir Dis 128:552–559.PubMedGoogle Scholar
  28. Westaby S (1983) Complement and the damaging effects of cardiopulmonary bypass. Thorax 38:321.PubMedCrossRefGoogle Scholar
  29. Westaby S (1986) Mechanisms of membrane damage and surfactant depletion in acute lung injury. Intensive Care Med 12:2–5.PubMedCrossRefGoogle Scholar
  30. Westaby S, Turner MW, Stark J (1984a) Complement activation, haemorrhagic pulmonary oedema and peripheral circulatory collapse following protamine administration in a child after cardiopulmonary bypass. Br Heart J 53:574–576.CrossRefGoogle Scholar
  31. Westaby S, Fleming J, Royston D (1984b) Evidence for generation of free radical species during cardiopulmonary bypass in man. In: Hagl S, Klovekorn WP, Mayr N, Sebering F (eds) Thirty years of extracorporeal circulation. Deutches Herzzentrum, Munich, p 389.Google Scholar
  32. Zaslow MC, Clark RA, Stone PJ, Calose JD, Snider GL, Franzblau C (1983) Human neutrophil elastase does not bind to alpha1-protease inhibitor that has been exposed to activated human neutrophils. Am Rev Respir Dis 128:434–439.PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1988

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  • S. Westaby

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