The role of the complement system in the pathogenesis of multiple organ failure in shock.

T. Zimmermann, Z. Laszik, S. Nagy, J. Kaszaki, F. Joo

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The results of our experiments suggest that the development of MOF is the result of a concerted autodestructive inflammatory process affecting the endothelium which is probably triggered off by the complement system. The combination of two noxious events (application of a low dose of endotoxin during hemorrhagic shock) leads to an enormous intravasal activation of complement including formation of C5a and the deposition of active split products of C3 (C3a, C3b) in the tissue of lung, liver, small intestine and kidney. Histological examination revealed ARDS-like pulmonary changes with inflammatory microvascular lesions and granulocytic infiltration primarily in the liver and to a lesser degree in the intestines and the kidney. The severity of organic lesion closely correlated with the extent of complement deposited. This corroborates the clinical observation that pulmonary and hepatic lesions are always the first signs of MOF, no matter what kind of noxious influence (trauma or peritonitis) gave rise to its development (Mc Menamy, 1980). Which mechanisms are involved in the processes by which active split products of C3 cause damage to tissue? C3a possesses strong chemotactic forces which can bring about aggregation of granulocytes in the tissue. Deposition of C3b on the contrary may lead to the formation of the cytolytically active membrane-attack-complex with the result of direct cell damage. We did not find any severe organic lesion or deposition of complement in our controls (endotoxin only, hemorrhage only). Our results suggest that MOF is a sequel of a generalized, autodestructive, inflammatory process which results from a hyperintensive and uncontrolled humoral immunoresponse to noxious events.(ABSTRACT TRUNCATED AT 250 WORDS)

Original languageEnglish
Pages (from-to)291-297
Number of pages7
JournalProgress in clinical and biological research
Publication statusPublished - 1989

ASJC Scopus subject areas

  • Medicine(all)

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