REGULATION OF THE FUNCTION OF THE FIRST COMPONENT OF COMPLEMENT BY HUMAN CLQ RECEPTOR

A membrane-associated receptor for the Clq subcomponent of complement is widely distributed among different cell types. While a number of po ssible physiological functions of the Clq receptor (C1qR) on different cell types have been described, the way in which C1qR regulates compl ement activity remains unclear. This report describes the mechanism by which C1qR regulates activation of the first component of complement, C1. Using purified components of complement, we were able to show tha t membrane-associated C1qR as well as detergent-solubilized C1qR, puri fied from polymorphonuclear leukocytes, human umbilical vein endotheli al cells or an endothelial cell line, EA.hy 926, are able to inhibit c omplement-mediated lysis of Clq-sensitized erythrocytes. Using hemolyt ic assays, we were able to demonstrate that C1qR prevents the associat ion of Clq with Clr and Cls to form macromolecular C1. In addition, in cubation of C1qR with the collagen-like stalks, but not with the globu lar heads of Clq, inhibits the effect of C1qR. This demonstrates that C1qR exerts its complement inhibitory effect by binding to the collage n-like stalk of Clq. No complement regulatory effect of C1qR was obser ved on preformed macromolecular C1. These data suggest that besides su ch well-known complement regulatory molecules as CD55 (DAF), CD46 (MCP ), CD35 (CR1) and CD59 (HRF), C1qR too is able to regulate complement activity.