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. 1998;7(6):417–420. doi: 10.1080/09629359990649

Acidosis activates complement system in vitro.

M Emeis 1, J Sonntag 1, C Willam 1, E Strauss 1, M M Walka 1, M Obladen 1
PMCID: PMC1781874  PMID: 9927235

Abstract

We investigated the in vitro effect of different forms of acidosis (pH 7.0) on the formation of anaphylatoxins C3a and C5a. Metabolic acidosis due to addition of hydrochloric acid (10 micromol/ml blood) or lactic acid (5.5 micromol/ml) to heparin blood (N=12) caused significant activation of C3a and C5a compared to control (both p=0.002). Respiratory acidosis activated C3a (p=0.007) and C5a (p=0.003) compared to normocapnic controls. Making blood samples with lactic acidosis hypocapnic resulted in a median pH of 7.37. In this respiratory compensated metabolic acidosis, C3a and C5a were not increased. These experiments show that acidosis itself and not lactate trigger for activation of complement components C3 and C5.

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Selected References

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  1. Brus F., van Oeveren W., Okken A., Bambang S. O. Activation of circulating polymorphonuclear leukocytes in preterm infants with severe idiopathic respiratory distress syndrome. Pediatr Res. 1996 Mar;39(3):456–463. doi: 10.1203/00006450-199603000-00013. [DOI] [PubMed] [Google Scholar]
  2. Buerke M., Murohara T., Lefer A. M. Cardioprotective effects of a C1 esterase inhibitor in myocardial ischemia and reperfusion. Circulation. 1995 Jan 15;91(2):393–402. doi: 10.1161/01.cir.91.2.393. [DOI] [PubMed] [Google Scholar]
  3. Burger R., Zilow G., Bader A., Friedlein A., Naser W. The C terminus of the anaphylatoxin C3a generated upon complement activation represents a neoantigenic determinant with diagnostic potential. J Immunol. 1988 Jul 15;141(2):553–558. [PubMed] [Google Scholar]
  4. Fishelson Z., Horstmann R. D., Müller-Eberhard H. J. Regulation of the alternative pathway of complement by pH. J Immunol. 1987 May 15;138(10):3392–3395. [PubMed] [Google Scholar]
  5. Hammer C. H., Hänsch G., Gresham H. D., Shin M. L. Activation of the fifth and sixth components of the human complement system: C6-dependent cleavage of C5 in acid and the formation of a bimolecular lytic complex, C5b,6a. J Immunol. 1983 Aug;131(2):892–898. [PubMed] [Google Scholar]
  6. Heideman M., Hugli T. E. Anaphylatoxin generation in multisystem organ failure. J Trauma. 1984 Dec;24(12):1038–1043. doi: 10.1097/00005373-198412000-00006. [DOI] [PubMed] [Google Scholar]
  7. Hill J., Lindsay T. F., Ortiz F., Yeh C. G., Hechtman H. B., Moore F. D., Jr Soluble complement receptor type 1 ameliorates the local and remote organ injury after intestinal ischemia-reperfusion in the rat. J Immunol. 1992 Sep 1;149(5):1723–1728. [PubMed] [Google Scholar]
  8. Horstick G., Heimann A., Götze O., Hafner G., Berg O., Böhmer P., Becker P., Darius H., Rupprecht H. J., Loos M. Intracoronary application of C1 esterase inhibitor improves cardiac function and reduces myocardial necrosis in an experimental model of ischemia and reperfusion. Circulation. 1997 Feb 4;95(3):701–708. doi: 10.1161/01.cir.95.3.701. [DOI] [PubMed] [Google Scholar]
  9. Ikai M., Itoh M., Joh T., Yokoyama Y., Okada N., Okada H. Complement plays an essential role in shock following intestinal ischaemia in rats. Clin Exp Immunol. 1996 Oct;106(1):156–159. doi: 10.1046/j.1365-2249.1996.d01-817.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Klos A., Ihrig V., Messner M., Grabbe J., Bitter-Suermann D. Detection of native human complement components C3 and C5 and their primary activation peptides C3a and C5a (anaphylatoxic peptides) by ELISAs with monoclonal antibodies. J Immunol Methods. 1988 Jul 22;111(2):241–252. doi: 10.1016/0022-1759(88)90133-0. [DOI] [PubMed] [Google Scholar]
  11. Rossen R. D., Michael L. H., Kagiyama A., Savage H. E., Hanson G., Reisberg M. A., Moake J. N., Kim S. H., Self D., Weakley S. Mechanism of complement activation after coronary artery occlusion: evidence that myocardial ischemia in dogs causes release of constituents of myocardial subcellular origin that complex with human C1q in vivo. Circ Res. 1988 Mar;62(3):572–584. doi: 10.1161/01.res.62.3.572. [DOI] [PubMed] [Google Scholar]
  12. Sonntag J., Emeis M., Strauss E., Obladen M. In vitro activation of complement and contact system by lactic acidosis. Mediators Inflamm. 1998;7(1):49–51. doi: 10.1080/09629359891388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sonntag J., Stiller B., Walka M. M., Maier R. F. Anaphylatoxins in fresh-frozen plasma. Transfusion. 1997 Aug;37(8):798–803. doi: 10.1046/j.1537-2995.1997.37897424401.x. [DOI] [PubMed] [Google Scholar]
  14. Sonntag J., Wagner M. H., Strauss E., Obladen M. Complement and contact activation in term neonates after fetal acidosis. Arch Dis Child Fetal Neonatal Ed. 1998 Mar;78(2):F125–F128. doi: 10.1136/fn.78.2.f125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Turnage R. H., Magee J. C., Guice K. S., Myers S. I., Oldham K. T. Complement activation by the hydroxyl radical during intestinal reperfusion. Shock. 1994 Dec;2(6):445–450. doi: 10.1097/00024382-199412000-00010. [DOI] [PubMed] [Google Scholar]
  16. Weiser M. R., Williams J. P., Moore F. D., Jr, Kobzik L., Ma M., Hechtman H. B., Carroll M. C. Reperfusion injury of ischemic skeletal muscle is mediated by natural antibody and complement. J Exp Med. 1996 May 1;183(5):2343–2348. doi: 10.1084/jem.183.5.2343. [DOI] [PMC free article] [PubMed] [Google Scholar]

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