Complement Inhibitor Therapeutics and Lung Injury

  • Una S. Ryan
Part of the NATO ASI Series book series (NSSA, volume 294)


Lung injury from any cause can have severe clinical outcomes. The Adult Respiratory Distress Syndrome (ARDS) was defined as a clinical entity in 1967.1 It is generally recognized as acute respiratory failure characterized by relatively normal cardiac function, an increase in vascular permeability leading to pulmonary edema manifested by diffuse pulmonary infiltrates on the chest X-ray and by a major oxygenation defect.2 Precipitating insults include severe sepsis, diffuse pneumonia, pancreatitis, multiple trauma, aspiration, near-drowning, burns, shock, hypotension, and coagulopathy. ARDS is a major contributor to the morbidity and mortality of patients in intensive care units with 30-day mortality rates varying from 55 to 65%.1–4 Current estimates are that more than 100,000 patients per year in the U.S. develop ARDS.5


Lung Injury Complement Activation Constitutive Function Complement Inhibitor Terminal Complex 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ashbaugh DG, Bigelow DB, Petty TL, and Levine BE. Acute respiratory distress in adults. Lancet 1967; ii: 319–323.CrossRefGoogle Scholar
  2. 2.
    Hyers TM. Prediction of survival and mortality in patients with adult respiratory distress syndrome. New Horizons 1993; 1:466–470.PubMedGoogle Scholar
  3. 3.
    Suchyta MR, Clemmer TP, Elliott CG, Orme JF, Jr., and Weaver LK. The adult respiratory distress syndrome: a report of survival and modifying factors. Chest 1992; 101:74–79.CrossRefGoogle Scholar
  4. 4.
    Artigas A, Calet J, Legall JR, et. al. Clinical presentation, prognostic factors and outcome of ARDS in the European Collaborative study (1985–1987). A preliminary report. In: Zapol W, LeMaire F, editors. Adult Respiratory Distress Syndrome, New York: Marcell Dekker, 1991:37–64.Google Scholar
  5. 5.
    Wheeler AP, Carroll FE, Bernard GR. Radiographic issues in adult respiratory distress syndrome. New Horizons 1993; 1:471–477.PubMedGoogle Scholar
  6. 6.
    Ryan US. Structural bases for metabolic activity. Ann Rev Physiol 1982; 44:223–239.CrossRefGoogle Scholar
  7. 7.
    Ryan US, Ryan JW. Vital and functional activities of endothelial cells. In: Nossel HL, Vogel HJ, editors. Pathobiology of the Endothelial Cell. New York: Academic Press, 1982:455–469.Google Scholar
  8. 8.
    Ryan US, Ryan JW, Whitaker C, and Chiu A. Localization of angiotensin converting enzyme (kininase II): immunocytochemistry and immunofluorescence. Tissue & Cell 1976; 8:125–146.CrossRefGoogle Scholar
  9. 9.
    Crutchley DJ, Ryan JW, Ryan US, and Fisher GH. Bradykinin-induced release of prostacyclin and thromboxanes from bovine pulmonary artery endothelial cells. Studies with lower homologs and calcium antagonists. Biochem Biophys Acta 1983; 751:99–107.PubMedCrossRefGoogle Scholar
  10. 10.
    Furchgott RF and Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetycholine. Nature 1980; 373:299.Google Scholar
  11. 11.
    Yanagisawa M, Kurihara H, Kimura S, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988; 332:411–415.PubMedCrossRefGoogle Scholar
  12. 12.
    American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992; 20:864–874.CrossRefGoogle Scholar
  13. 13.
    Zilow G, Joka T, Obertacke U, Rother U, and Kirschfink M. Generation of anaphylatoxin C3a in plasma and bronchoalveolar lavage fluid in trauma patients at risk for the adult respiratory distress syndrome. Crit Care Med 1992; 20:468–473.PubMedCrossRefGoogle Scholar
  14. 14.
    Hamilton KK, Hattori R, Esmon CT, and Sims PJ. Complement proteins C5b-9 induce vesiculation of the endothelial plasma membrane and expose catalytic surface for assembly of the prothrombinase enzyme complex. J Biol Chem 1990; 265:3809–3814.PubMedGoogle Scholar
  15. 15.
    Halperin JA, Taratuska A, Nicholson-Weller A. Terminal complement complex C5b-9 stimulates mitogenesis in 3T3 cells. J Clin Invest 1993; 91:1974–1978.PubMedCrossRefGoogle Scholar
  16. 16.
    Benzaquen LR, Nicholson-Weller A, and Halperin JA. Terminal complement proteins C5b-9 release basic fibroblast growth factor and platelet-derived growth factor from endothelial cells. J Exp Med 1994; 179:985–992.PubMedCrossRefGoogle Scholar
  17. 17.
    Mulligan MS, Yeh CG, Rudolph AR, and Ward PA. Protective effects of soluble CR1 in complement-and neutrophil-mediated tissue injury. J Immunol 1992; 148:1479–1485.PubMedGoogle Scholar
  18. 18.
    Rabinovici R., Yeh CG, Hillegass LM, Griswold DC, DiMartino MJ, Vernick J, et al. Role of complement in endotoxin/platelet-activating factor-induced lung injury. J Immunol 1992; 149:1744–1750.PubMedGoogle Scholar
  19. 19.
    DiMartino MJ, Wolfe CE, Slivjak MJ, Minthorn EA, Feuerstein G. Effects of soluble complement receptor (sCR1, BRL55730) on thermal skin injury induced hemoconcentration and lung inflammation in rats. Pharmacol Commun 1993; 3:249–256.Google Scholar
  20. 20.
    Weisman HF, Bartow T, Leppo MK, et. al. Soluble human complement receptor type 1: In vivo inhibitor of complement suppressing post-ischemic myocardial inflammation and necrosis. Science 1990; 249:146–151.PubMedCrossRefGoogle Scholar
  21. 21.
    Smith EF, III, Griswold DE, Egan JW, Hillegass LM, Smith RAG, Hibbs MJ, et al. Reduction of myocardial reperfusion injury with soluble complement receptor I (BRL 55730). Eur J Pharmacol 1993; 236:477–481.PubMedCrossRefGoogle Scholar
  22. 22.
    Dupe RJ, Goddard ME, Freeman AM, Hibbs MJ, Lifter J, Mossakowska DE, et al. Utility of complement inhibition during myocardial reperfusion: Pharmacology of soluble complement receptor 1. 13th Congress of the International Society of Thrombosis and Haemostasis. Thrombos Haemostasis 1991; 65:695.Google Scholar
  23. 23.
    Schaiff WT and Eisenberg PR. Pharmacologie activation of plasminogen directly induces and enhances complement activation. Suppl. to Circulation 1995; 92:I–342 Abstract.Google Scholar
  24. 24.
    Naka Y, Roy DK, Marsh HC, et. al. Protective effects of complement blockade in an isograft model of lung preservation and transplantation. Am Col of Cardiology 45th Annual Scientific Symposium 1996; Abstract.Google Scholar
  25. 25.
    Pruitt SK and Bollinger RR. The effect of soluble complement receptor type I on hyperacute allograft rejection. J Surg Res 1991; 50:350–355.PubMedCrossRefGoogle Scholar
  26. 26.
    Pruitt SK, Baldwin WM, Marsh HC, Jr., Lin SS, Yeh CG, Bollinger RR. The effect of soluble complement receptor type I on hyperacute xenograft rejection. Transplantation 1991; 52:868–873.PubMedCrossRefGoogle Scholar
  27. 27.
    Pruitt SK, Kirk AD, Bollinger RR, Marsh HC, Jr., Collins BH, Levin JL, et al. The effect of soluble complement receptor type I on hyperacute rejection of porcine xenografts. Transplantation 1994; 57:363–370.PubMedCrossRefGoogle Scholar
  28. 28.
    Davis EA, Pruitt SK, Greene PS, Ibrahim S, Lam TT, Levin JL, et al. Inhibition of complement, evoked antibody, and cellular response prevents rejection of pig-to-primate cardiac xenografts. Transplantation 1996; 62:1018–1023.PubMedCrossRefGoogle Scholar
  29. 29.
    Pratt JR, Hibbs MJ, Laver AJ, Smith RAG, Sacks SH. Allograft immune response with sCR1 intervention. Transplant Immunol 1996; 4:72–75.CrossRefGoogle Scholar
  30. 30.
    Pratt JR, Harmer AW, Smith RAG, and Sacks SH. Influence of complement inhibition with soluble complement receptor (sCR1) on the B cell response in experimental allograft rejection. Transplantation Society 1996; Barcelona, Spain: Abstract.Google Scholar
  31. 31.
    Kallio E, Koskinen P, Krebs R, Ryan U, Hayry P, and Lemstrom K. Soluble recombinant complement receptor type 1 significantly reduces the development of experimental obliterative bronchiolitis in rat tracheal allografts. Int Transplantation Society 1996; Abstract.Google Scholar
  32. 32.
    Ryan US. Complement inhibitory therapeutics and xenotransplantation. Nature Medicine 1995; 1:967–968.PubMedCrossRefGoogle Scholar
  33. 33.
    Ryan US. Complement inhibition: the sine qua non of xenotransplantation? Xeno 1994; 2:19–22.Google Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Una S. Ryan
    • 1
  1. 1.T Cell Sciences, Inc.NeedhamUSA

Personalised recommendations