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J Clin Invest. 1986 June; 77(6): 1812–1816.
PMCID: PMC370538

Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates.

Abstract

In vitro and in vivo studies have suggested that human complement component C5a plays a key role in neutrophil injury in the adult respiratory distress syndrome (ARDS). First, using leukocyte aggregometry, we demonstrated that the addition of a recently developed rabbit anti-human polyclonal antibody to C5a des arg to endotoxin-activated plasma prevented leukocyte aggregation in vitro. We then administered the anti-C5a des arg antibody to septic primates (Macaca fascicularis). Three groups of primates, control, septic, and anti-C5a antibody treated septic, were studied (n = 4 in each group). A 30-min infusion of Escherichia coli (1 X 10(10)/kg) resulted in severe sepsis and ARDS. Primates were killed 4 h after completion of the E. coli infusion. Septic animals not treated with anti-C5a antibody had 75% mortality (3/4), decreased oxygenation, severe pulmonary edema, and profound hypotension. Septic primates treated with anti-C5a antibodies did not die and did not develop decreased oxygenation (P less than 0.05) or increased extravascular lung water (P less than 0.05). They also had a marked recovery in their mean arterial blood pressure (P less than 0.05). This study demonstrates that treatment with rabbit anti-human C5a des arg antibodies attenuates ARDS and some of the systemic manifestations of sepsis in nonhuman primates.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Fowler AA, Hamman RF, Good JT, Benson KN, Baird M, Eberle DJ, Petty TL, Hyers TM. Adult respiratory distress syndrome: risk with common predispositions. Ann Intern Med. 1983 May;98(5 Pt 1):593–597. [PubMed]
  • Fein AM, Lippmann M, Holtzman H, Eliraz A, Goldberg SK. The risk factors, incidence, and prognosis of ARDS following septicemia. Chest. 1983 Jan;83(1):40–42. [PubMed]
  • Stevens JH, Raffin TA. Adult respiratory distress syndrome--I. Aetiology and mechanisms. Postgrad Med J. 1984 Aug;60(706):505–513. [PMC free article] [PubMed]
  • Sacks T, Moldow CF, Craddock PR, Bowers TK, Jacob HS. Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes. An in vitro model of immune vascular damage. J Clin Invest. 1978 May;61(5):1161–1167. [PMC free article] [PubMed]
  • Craddock PR, Hammerschmidt D, White JG, Dalmosso AP, Jacob HS. Complement (C5-a)-induced granulocyte aggregation in vitro. A possible mechanism of complement-mediated leukostasis and leukopenia. J Clin Invest. 1977 Jul;60(1):260–264. [PMC free article] [PubMed]
  • Hammerschmidt DE, Bowers TK, Lammi-Keefe CJ, Jacob HS, Craddock PR. Granulocyte aggregometry: a sensitive technique for the detection of C5a and complement activation. Blood. 1980 Jun;55(6):898–902. [PubMed]
  • Tonnesen MG, Smedly LA, Henson PM. Neutrophil-endothelial cell interactions. Modulation of neutrophil adhesiveness induced by complement fragments C5a and C5a des arg and formyl-methionyl-leucyl-phenylalanine in vitro. J Clin Invest. 1984 Nov;74(5):1581–1592. [PMC free article] [PubMed]
  • Hosea S, Brown E, Hammer C, Frank M. Role of complement activation in a model of adult respiratory distress syndrome. J Clin Invest. 1980 Aug;66(2):375–382. [PMC free article] [PubMed]
  • Gelfand JA, Donelan M, Hawiger A, Burke JF. Alternative complement pathway activation increases mortality in a model of burn injury in mice. J Clin Invest. 1982 Dec;70(6):1170–1176. [PMC free article] [PubMed]
  • Parrish DA, Mitchell BC, Henson PM, Larsen GL. Pulmonary response of fifth component of complement-sufficient and -deficient mice to hyperoxia. J Clin Invest. 1984 Sep;74(3):956–965. [PMC free article] [PubMed]
  • Hammerschmidt DE, Weaver LJ, Hudson LD, Craddock PR, Jacob HS. Association of complement activation and elevated plasma-C5a with adult respiratory distress syndrome. Pathophysiological relevance and possible prognostic value. Lancet. 1980 May 3;1(8175):947–949. [PubMed]
  • Hugli TE, Gerard C, Kawahara M, Scheetz ME, 2nd, Barton R, Briggs S, Koppel G, Russell S. Isolation of three separate anaphylatoxins from complement-activated human serum. Mol Cell Biochem. 1981 Dec 4;41:59–66. [PubMed]
  • Wechter WJ, Nelson JW, Perper RJ, Parcells AJ, Riebe KW, Evans JS, Satoh PS, Ko H. Manufacture of antithymocyte globulin (ATGAM) for clinical trials. Transplantation. 1979 Oct;28(4):303–307. [PubMed]
  • Hull RA, Gill RE, Hsu P, Minshew BH, Falkow S. Construction and expression of recombinant plasmids encoding type 1 or D-mannose-resistant pili from a urinary tract infection Escherichia coli isolate. Infect Immun. 1981 Sep;33(3):933–938. [PMC free article] [PubMed]
  • O'Hanley P, Lark D, Falkow S, Schoolnik G. Molecular basis of Escherichia coli colonization of the upper urinary tract in BALB/c mice. Gal-Gal pili immunization prevents Escherichia coli pyelonephritis in the BALB/c mouse model of human pyelonephritis. J Clin Invest. 1985 Feb;75(2):347–360. [PMC free article] [PubMed]
  • Mihm FG, Feeley TW, Rosenthal MH, Lewis F. Measurement of extravascular lung water in dogs using the thermal-green dye indicator dilution method. Anesthesiology. 1982 Aug;57(2):116–122. [PubMed]
  • Starkebaum G, Jimenez RA, Arend WP. Effect of immune complexes on human neutrophil phagocytic function. J Immunol. 1982 Jan;128(1):141–147. [PubMed]

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