Regulation of the function of the first component of complement by human C1q receptor.
A membrane-associated receptor for the C1q subcomponent of complement is widely distributed among different cell types. While a number of possible physiological functions of the C1q receptor (C1qR) on different cell types have been described, the way in which C1qR regulates complement 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 that membrane-associated C1qR as well as detergent-solubilized C1qR, purified from polymorphonuclear leukocytes, human umbilical vein endothelial cells or an endothelial cell line, EA.hy 926, are able to inhibit complement-mediated lysis of C1q-sensitized erythrocytes. Using hemolytic assays, we were able to demonstrate that C1qR prevents the association of C1q with C1r and C1s to form macromolecular C1. In addition, incubation of C1qR with the collagen-like stalks, but not with the globular heads of C1q, inhibits the effect of C1qR. This demonstrates that C1qR exerts its complement inhibitory effect by binding to the collagen-like stalk of C1q. No complement regulatory effect of C1qR was observed on preformed macromolecular C1. These data suggest that besides such-well-known complement regulatory molecules as CD55 (DAF), CD46 (MCP), CD35 (CR1) and CD59 (HRF), C1qR too is able to regulate complement activity.
van den Berg
R H
RH
Department of Nephrology, University Hospital Leiden, The Netherlands.
Faber-Krol
M
M
van Es
L A
LA
Daha
M R
MR
D002352:Carrier Proteins; D003174:Complement C1 Inactivator Proteins / Q000502:physiology*; D015922:Complement C1q / Q000037:antagonists & inhibitors; D015923:Complement C1r / Q000037:antagonists & inhibitors; D003173:Complement C1s / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D009504:Neutrophils / Q000502:physiology; D011951:Receptors, Complement / Q000502:physiology*
C087299:C1QBP protein, human; D002352:Carrier Proteins; D003174:Complement C1 Inactivator Proteins; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement; C032402:complement 1q receptor; D015922:Complement C1q; D015923:Complement C1r; D003173:Complement C1s