Electron microscopic studies demonstrated that lesions were produced on the endotoxic lipopolysaccharide (LPS) as well as on the cell surface of V. alcalescens after reaction with fresh guinea pig serum. These lesions were approximately 90 A in diameter, and were seen on two characteristic structural entities derived from LPS preparations after incubation with serum. The use of numerous inhibitors, inactivators, and reaction conditions affecting hemolytic C' activity revealed that these lesions were mediated by the C' system. Concomitant with lesion formation, C' was fixed; the effect on classical C'3 activity was pronounced. It is concluded that endotoxic LPS, as contained in the outer three-layered membrane of the bacterial cell, is a substrate for the C' enzymes. It is suggested that certain biological activities of endotoxin may derive from its effects on the C' system.

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