Complement receptor is an inhibitor of the complement cascade.
A glycoprotein from the membrane of human erythrocytes has been identified as a receptor for C3b (CR1). It promotes the dissociation of the alternative pathway C3 convertase C3b,Bb and the cleavage of C3b by C3b/C4b inactivator. We find that CR1 also inactivates the C3 and C5 convertases of the classical pathway. CR1 inhibits the consumption of C3 by C3 convertase EAC142 and enhances the decay of C4b,2a sites. On a weight basis, CR1 is approximately 5-10 times more active than C4 binding protein, a serum inhibitor of C4b,2a. The binding of 125I-CR1 to EAC14 cells is inhibited by C2. Therefore, it is likely that CR1 and C2 compete for a site on C4b. CR1 inhibited C5 convertase even more effectively, but had no effect on the assembly of the late complement components. At high concentrations, CR1 alone has no irreversible effects on cell-bound C4b. In the fluid phase, CR1 can function as a cofactor for the cleavage of the alpha' chain of C4b by C3b/C4b inactivator. A well-known function of CR1 is to promote adherence of microbes or immune complexes bearing C3b and C4b to cells. This interaction could result in a microenvironment damaging to the plasma membrane of the responding cell because the extrinsic C3b and C4b fragments can serve as additional sites of assembly of enzymes of the cascade. We therefore wish to propose that CR1 on the surface of cells supplies an increased local concentration of a strong inhibitor of the amplifying enzymes of the complement system and provides cells with a mechanism for circumventing damage when they bind C3b- and C4b-bearing substrates.
D050577:Complement C3-C5 Convertases / Q000037:antagonists & inhibitors; D003181:Complement C4 / Q000037:antagonists & inhibitors; D003182:Complement C5 / Q000037:antagonists & inhibitors; D003169:Complement Inactivator Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D003171:Complement Pathway, Classical; D004910:Erythrocyte Membrane / Q000032:analysis; D006801:Humans; D011951:Receptors, Complement / Q000502:physiology*
D003181:Complement C4; D003182:Complement C5; D003169:Complement Inactivator Proteins; D011951:Receptors, Complement; D050577:Complement C3-C5 Convertases