SOLUBLE HUMAN-COMPLEMENT RECEPTOR-TYPE-1 INHIBITS COMPLEMENT-MEDIATEDHOST-DEFENSE

Soluble complement receptor type 1 (sCR1) is a powerful inhibitor of c omplement activation. Because of this ability, sCR1 may prove to be an important therapeutic agent that can be used to block the immunopatho logic effects of uncontrolled complement activation in a variety of cl inically significant disorders. Although several previous studies have examined the ability of sCR1 to inhibit complement-mediated immunopat hologic damage, there is no information on its ability to interfere wi th the host's defense against infection. In the current experiments sC R1 exerted a concentration-dependent inhibitory effect on the phagocyt osis of Strepto-coccus pneumoniae by human polymorphonuclear leukocyte s in vitro. Not only did sCR1 inhibit complement-dependent opsonizatio n of the pneumococcus but a higher concentrations it also inhibited th e ingestion of bacteria which had been previously opsonized. Furthermo re, when rats were injected with sCR1, it inhibited both their serum h emolytic activity and serum opsonic activity in a dose-dependent fashi on. Finally, for rats treated with sCR1, the 50% lethal dose was also shown to be significantly lower than that for control animals after in travenous challenge with S. pneumoniae and Pseudomonas aeruginosa. The se data demonstrate that sCR1 significantly inhibits complement-mediat ed host defense against bacterial infection.