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The Requirement for Serum Complement in the Detoxification of Bacterial Endotoxin¹

Department of Pathology, University of Connecticut Health Center, Farmington, Connecticut 06032

Abstract

The in vitro detoxification of bacterial endotoxin requires both the fifth (C5) and and sixth (C6) components of complement and proceeds in the presence of 0.01 M EDTA. Addition of purified C5 or C6 to the genetically deficient serum corrects the defect in detoxification of endotoxin. Mice lacking C5 show a greatly increased susceptibility to the lethal effects of endotoxin and C6 deficient rabbits, in contrast to normal rabbits, fail to develop an increased detoxifying capacity in serum as a result of recent exposure to endotoxin. While human plasma is more effective than serum in detoxifying endotoxin, this cannot be completely ascribed to the reduction in levels of cations. The mechanism by which the complement system participates in the detoxification of endotoxin is peculiarly different from the usual sequential pathways of the complement system. In broad biologic terms, these findings suggest a previously unrecognized, protective function of the complement system.

Footnotes

¹ This work was supported by National Institutes of Health Grant AI 09651-01.