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. 1988 Jul 1;168(1):443–448. doi: 10.1084/jem.168.1.443

C5a stimulates secretion of tumor necrosis factor from human mononuclear cells in vitro. Comparison with secretion of interleukin 1 beta and interleukin 1 alpha

PMCID: PMC2188974  PMID: 3260938

Abstract

We have demonstrated that purified C5a is a potent stimulus to human PBMC secretion of TNF-alpha, IL-1 beta, and IL-1 alpha, which proceeds in a dose-dependent fashion. At a given concentration of C5a, TNF-alpha and IL-1 beta secretion did not differ significantly; both were secreted in significantly greater quantity than IL-1 alpha. Clinical conditions such as Gram-positive and Gram-negative bacterial infections, trauma, and immune complex diseases activate complement. Through the mediation of TNF and IL-1 secreted in response to C5a, these diverse disorders can share common features of fever, coagulopathy, acute phase protein production, and disordered metabolism.

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Selected References

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  1. Beutler B., Cerami A. Cachectin: more than a tumor necrosis factor. N Engl J Med. 1987 Feb 12;316(7):379–385. doi: 10.1056/NEJM198702123160705. [DOI] [PubMed] [Google Scholar]
  2. Beutler B., Krochin N., Milsark I. W., Luedke C., Cerami A. Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance. Science. 1986 May 23;232(4753):977–980. doi: 10.1126/science.3754653. [DOI] [PubMed] [Google Scholar]
  3. Beutler B., Milsark I. W., Cerami A. C. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science. 1985 Aug 30;229(4716):869–871. doi: 10.1126/science.3895437. [DOI] [PubMed] [Google Scholar]
  4. Clancy R. M., Dahinden C. A., Hugli T. E. Arachidonate metabolism by human polymorphonuclear leukocytes stimulated by N-formyl-Met-Leu-Phe or complement component C5a is independent of phospholipase activation. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7200–7204. doi: 10.1073/pnas.80.23.7200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dinarello C. A. Interleukin-1: amino acid sequences, multiple biological activities and comparison with tumor necrosis factor (cachectin). Year Immunol. 1986;2:68–89. [PubMed] [Google Scholar]
  6. Dinarello C. A., Mier J. W. Lymphokines. N Engl J Med. 1987 Oct 8;317(15):940–945. doi: 10.1056/NEJM198710083171506. [DOI] [PubMed] [Google Scholar]
  7. Duff G. W., Atkins E. The detection of endotoxin by in vitro production of endogenous pyrogen: comparison with limulus amebocyte lysate gelation. J Immunol Methods. 1982 Aug 13;52(3):323–331. doi: 10.1016/0022-1759(82)90004-7. [DOI] [PubMed] [Google Scholar]
  8. Goodman M. G., Chenoweth D. E., Weigle W. O. Induction of interleukin 1 secretion and enhancement of humoral immunity by binding of human C5a to macrophage surface C5a receptors. J Exp Med. 1982 Sep 1;156(3):912–917. doi: 10.1084/jem.156.3.912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hammerschmidt D. E., Weaver L. J., Hudson L. D., Craddock P. R., Jacob H. S. 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. doi: 10.1016/s0140-6736(80)91403-8. [DOI] [PubMed] [Google Scholar]
  10. Hugli T. E., Müller-Eberhard H. J. Anaphylatoxins: C3a and C5a. Adv Immunol. 1978;26:1–53. doi: 10.1016/s0065-2776(08)60228-x. [DOI] [PubMed] [Google Scholar]
  11. José P. J., Forrest M. J., Williams T. J. Human C5a des Arg increases vascular permeability. J Immunol. 1981 Dec;127(6):2376–2380. [PubMed] [Google Scholar]
  12. Lisi P. J., Chu C. W., Koch G. A., Endres S., Lonnemann G., Dinarello C. A. Development and use of a radioimmunoassay for human interleukin-1 beta. Lymphokine Res. 1987 Summer;6(3):229–244. [PubMed] [Google Scholar]
  13. Morgan E. L., Thoman M. L., Weigle W. O., Hugli T. E. Anaphylatoxin-mediated regulation of the immune response. II. C5a-mediated enhancement of human humoral and T cell-mediated immune responses. J Immunol. 1983 Mar;130(3):1257–1261. [PubMed] [Google Scholar]
  14. Movat H. Z., Burrowes C. E., Cybulsky M. I., Dinarello C. A. Acute inflammation and a Shwartzman-like reaction induced by interleukin-1 and tumor necrosis factor. Synergistic action of the cytokines in the induction of inflammation and microvascular injury. Am J Pathol. 1987 Dec;129(3):463–476. [PMC free article] [PubMed] [Google Scholar]
  15. Ognibene F. P., Martin S. E., Parker M. M., Schlesinger T., Roach P., Burch C., Shelhamer J. H., Parrillo J. E. Adult respiratory distress syndrome in patients with severe neutropenia. N Engl J Med. 1986 Aug 28;315(9):547–551. doi: 10.1056/NEJM198608283150904. [DOI] [PubMed] [Google Scholar]
  16. Okusawa S., Dinarello C. A., Yancey K. B., Endres S., Lawley T. J., Frank M. M., Burke J. F., Gelfand J. A. C5a induction of human interleukin 1. Synergistic effect with endotoxin or interferon-gamma. J Immunol. 1987 Oct 15;139(8):2635–2640. [PubMed] [Google Scholar]
  17. Okusawa S., Gelfand J. A., Ikejima T., Connolly R. J., Dinarello C. A. Interleukin 1 induces a shock-like state in rabbits. Synergism with tumor necrosis factor and the effect of cyclooxygenase inhibition. J Clin Invest. 1988 Apr;81(4):1162–1172. doi: 10.1172/JCI113431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Renfer L., Frank M. M., Hammer C. H., Harvath L., Lawley T. J., Yancey K. B. A simplified method for purification of human C5a from citrated plasma. J Immunol Methods. 1986 Apr 17;88(2):193–205. doi: 10.1016/0022-1759(86)90006-2. [DOI] [PubMed] [Google Scholar]
  19. Scuderi P., Sterling K. E., Lam K. S., Finley P. R., Ryan K. J., Ray C. G., Petersen E., Slymen D. J., Salmon S. E. Raised serum levels of tumour necrosis factor in parasitic infections. Lancet. 1986 Dec 13;2(8520):1364–1365. doi: 10.1016/s0140-6736(86)92007-6. [DOI] [PubMed] [Google Scholar]
  20. Tracey K. J., Beutler B., Lowry S. F., Merryweather J., Wolpe S., Milsark I. W., Hariri R. J., Fahey T. J., 3rd, Zentella A., Albert J. D. Shock and tissue injury induced by recombinant human cachectin. Science. 1986 Oct 24;234(4775):470–474. doi: 10.1126/science.3764421. [DOI] [PubMed] [Google Scholar]
  21. Waage A., Halstensen A., Espevik T. Association between tumour necrosis factor in serum and fatal outcome in patients with meningococcal disease. Lancet. 1987 Feb 14;1(8529):355–357. doi: 10.1016/s0140-6736(87)91728-4. [DOI] [PubMed] [Google Scholar]
  22. Weinberg P. F., Matthay M. A., Webster R. O., Roskos K. V., Goldstein I. M., Murray J. F. Biologically active products of complement and acute lung injury in patients with the sepsis syndrome. Am Rev Respir Dis. 1984 Nov;130(5):791–796. doi: 10.1164/arrd.1984.130.5.791. [DOI] [PubMed] [Google Scholar]
  23. van der Meer J. W., Endres S., Lonnemann G., Cannon J. G., Ikejima T., Okusawa S., Gelfand J. A., Dinarello C. A. Concentrations of immunoreactive human tumor necrosis factor alpha produced by human mononuclear cells in vitro. J Leukoc Biol. 1988 Mar;43(3):216–223. doi: 10.1002/jlb.43.3.216. [DOI] [PubMed] [Google Scholar]

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