Serum contains an activity termed C-INH which inhibits the attachment of the C complex of complement to bystander cells. The serum constituents which express this activity have not yet been defined. The present studies were initiated to examine the possibility that serum lipoproteins have C-INH activity. Lipoproteins were prepared by sequential flotations and were free of other proteins detectable by immunochemical procedures; they comprised 3% of the serum proteins but accounted for approximately 25% of the serum C-INH activity. The lipoproteins selectively inhibited the attachment of C to bystander cells by interacting with C in solution; they did not inhibit either the formation of C from C and C7 or the lysis of preformed EC by limiting amounts of C8 and C9. Furthermore, the lipoproteins did not inhibit the complement-mediated hemolysis of EA or EAC. Inhibitory activity was found in each of the three major lipoprotein density classes, with the high density lipoproteins having the greatest specific activity. Poly-L-lysine, previously shown to counteract serum -INH also partially blocked the inhibitory activity of the lipoproteins. These experiments point to lipoproteins as a major constituent of serum -INH, and emphasize that lipoproteins exercise a potentially important modulating effect upon the complement membrane attack mechanism.

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This work was supported by grants from the Leukemia Research Foundation, Inc., the Hunter Trust, and the Chicago Heart Association; presented in part at the Annual Meetings of the Central Society for Clinical Investigation, November 2, 1975 (1), and the American Association of Immunologists, April 13, 1976 (2).

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