Cholesterol and atheroma lipids activate complement and stimulate granulocytes. A possible mechanism for amplification of ischemic injury in atherosclerotic states

Dale E. Hammerschmidt, Charles S. Greenberg, Osamu Yamada, Philip R. Craddock, Harry S. Jacob

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Previous studies in experimental myocardial infarction have suggested that PMNs and plasma C might interact to intensify ischemic injury. From the finding of large amounts of activated C (specifically C5a) in the plasma of a patient with severe, ulcerating atherosclerosis and the cholesterol embolization syndrome, we postulated that crystalline cholesterol might activate C and thereby amplify infarctive tissue damage. On simple incubation, crystalline cholesterol-as well as lipids from atheromata-activated plasma C; such plasma then potently aggregated normal PMNs and provoked them to damage cultured endothelial cells in vitro. The active principle in cholesterol-incubated plasma was of molecular weight and antigenicity consistent with C5a (or C5a[desarginine]). Optimal activation required the presence of Ig and an intact classical C pathway. Exposure of plasma to crystalline cholesterol by ulceration of, or hemorrhage into, atherosclerotic plaques might therefore activate C in vivo, promoting further ischemic damage by causing leukostatic-leukoembolic compromise of small vessels downstream from the site of activation.

Original languageEnglish (US)
Pages (from-to)68-77
Number of pages10
JournalThe Journal of laboratory and clinical medicine
Volume98
Issue number1
StatePublished - Jul 1981

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