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. 1971 Oct 31;134(5):1131–1143. doi: 10.1084/jem.134.5.1131

BIOLOGICAL ACTIVITY OF COMPLEMENT IN VIVO

ROLE OF C5 IN THE ACCUMULATION OF POLYMORPHONUCLEAR LEUKOCYTES IN INFLAMMATORY EXUDATES

Ralph Snyderman 1, Jean K Phillips 1, Stephan E Mergenhagen 1
PMCID: PMC2139022  PMID: 5112201

Abstract

The importance of C5 in the generation of complement (C)-dependent chemotactic activity in vitro is well recognized. However, the actual role C5 may play in the accumulation of polymorphonuclear leukocytes (PMN) at inflammatory sites in vivo has not been established. Injection of glycogen or endotoxin into the peritoneal cavities of guinea pigs resulted, shortly thereafter, in the local accumulation of PMN. Preceding the influx of leukocytes, the peritoneal fluid became chemotactic for rabbit PMN in vitro. The majority of this activity could be attributed to a cleavage product of C5 (C5a). Similarly, injection of endotoxin into the peritoneal cavity of C5-normal mice resulted in the generation of a chemotactic factor for mouse PMN which was followed by the accumulation of PMN in the peritoneal fluid. In contrast, injection of endotoxin into the peritoneal cavity of C5-deficient mice resulted in the generation of virtually no detectable chemotactic activity and a markedly depressed accumulation of PMN during the first 24 hr after injection. The data suggest that C5 plays an important role in the early phases of PMN accumulation in response to inflammatory stimuli. The rapid accumulation of PMN in response to an inflammatory stimulus such as bacterial endotoxin would be expected to be a major factor in host defense against proliferation and dissemination of infectious agents.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BEN-EFRAIM S., CINADER B. THE ROLE OF COMPLEMENT IN THE PASSIVE CUTANEOUS REACTION OF MICE. J Exp Med. 1964 Nov 1;120:925–942. doi: 10.1084/jem.120.5.925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BOYDEN S. The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leucocytes. J Exp Med. 1962 Mar 1;115:453–466. doi: 10.1084/jem.115.3.453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Caren L. D., Rosenberg L. T. The role of complement in resistance to endogenous and exogenous infection with a common mouse pathogen, Corynebacterium kutscheri. J Exp Med. 1966 Oct 1;124(4):689–699. doi: 10.1084/jem.124.4.689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cochrane C. G. Immunologic tissue injury mediated by neutrophilic leukocytes. Adv Immunol. 1968;9:97–162. doi: 10.1016/s0065-2776(08)60442-3. [DOI] [PubMed] [Google Scholar]
  5. HIRSCH J. G., CHURCH A. B. Studies of phagocytosis of group A streptococci by polymorphonuclear leucocytes in vitro. J Exp Med. 1960 Mar 1;111:309–322. doi: 10.1084/jem.111.3.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Mergenhagen S. E., Snyderman R., Gewurz H., Shin H. S. Significance of complement to the mechanism of action of endotoxin. Curr Top Microbiol Immunol. 1969;50:37–77. doi: 10.1007/978-3-642-46169-9_2. [DOI] [PubMed] [Google Scholar]
  7. Morelli R., Rosenberg L. T. Role of complement during experimental Candida infection in mice. Infect Immun. 1971 Apr;3(4):521–523. doi: 10.1128/iai.3.4.521-523.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Müller-Eberhard H. J. Chemistry and reaction mechanisms of complement. Adv Immunol. 1968;8:1–80. doi: 10.1016/s0065-2776(08)60464-2. [DOI] [PubMed] [Google Scholar]
  9. Ratnoff O. D. Some relationships among hemostasis, fibrinolytic phenomena, immunity, and the inflammatory response. Adv Immunol. 1969;10:145–227. doi: 10.1016/s0065-2776(08)60417-4. [DOI] [PubMed] [Google Scholar]
  10. Shin H. S., Smith M. R., Wood W. B., Jr Heat labile opsonins to pneumococcus. II. Involvement of C3 and C5. J Exp Med. 1969 Dec 1;130(6):1229–1241. doi: 10.1084/jem.130.6.1229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Shin H. S., Snyderman R., Friedman E., Mellors A., Mayer M. M. Chemotactic and anaphylatoxic fragment cleaved from the fifth component of guinea pig complement. Science. 1968 Oct 18;162(3851):361–363. doi: 10.1126/science.162.3851.361. [DOI] [PubMed] [Google Scholar]
  12. Snyderman R., Gewurz H., Mergenhagen S. E. Interactions of the complement system with endotoxic lipopolysaccharide. Generation of a factor chemotactic for polymorphonuclear leukocytes. J Exp Med. 1968 Aug 1;128(2):259–275. doi: 10.1084/jem.128.2.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Snyderman R., Phillips J., Mergenhagen S. E. Polymorphonuclear leukocyte chemotactic activity in rabbit serum and Guinea pig serum treated with immune complexes: evidence for c5a as the major chemotactic factor. Infect Immun. 1970 Jun;1(6):521–525. doi: 10.1128/iai.1.6.521-525.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Snyderman R., Shin H. S., Hausman M. H. A chemotactic factor for mononuclear leukocytes. Proc Soc Exp Biol Med. 1971 Nov;138(2):387–390. doi: 10.3181/00379727-138-35903. [DOI] [PubMed] [Google Scholar]
  15. Snyderman R., Shin H. S., Phillips J. K., Gewurz H., Mergenhagen S. E. A neutrophil chemotatic factor derived from C'5 upon interaction of guinea pig serum with endotoxin. J Immunol. 1969 Sep;103(3):413–422. [PubMed] [Google Scholar]
  16. WARD P. A., COCHRANE C. G., MUELLER-EBERHARD H. J. THE ROLE OF SERUM COMPLEMENT IN CHEMOTAXIS OF LEUKOCYTES IN VITRO. J Exp Med. 1965 Aug 1;122:327–346. doi: 10.1084/jem.122.2.327. [DOI] [PMC free article] [PubMed] [Google Scholar]

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