Functional properties of membrane cofactor protein of complement.
Membrane cofactor protein (MCP or gp45-70) of the complement system is a cofactor for factor I-mediated cleavage of fluid-phase C3b and C3b-like C3, which opens the thioester bond. In the present study the activity of MCP was further characterized. Unexpectedly, in the absence of factor I, MCP stabilized the alternative- and, to a lesser extent, the classical-pathway cell-bound C3 convertases and thereby enhanced C3b deposition. Soluble MCP, if added exogenously, hardly functioned as cofactor for the cleavage of erythrocyte-bound C3b to iC3b; i.e. its activity, compared with the cofactor activity of factor H, was inefficient, since less than 10% of the bound C3b was MCP-sensitive. Further, exogenously added soluble MCP was also a weak cofactor for the cleavage of C3b bound to zymosan. Likewise, factor I, in the presence of cells bearing MCP, cleaved fluid-phase C3b inefficiently. These results imply that MCP has very little extrinsic cofactor activity for factor I. In contrast, exogenously added MCP and factor I mediated efficient cleavage of erythrocyte-bound C3b if the concentration of Nonidet P40 was sufficient to solubilize the cells. Interestingly, soluble MCP and factor I degraded C3b attached to certain solubilized acceptor membrane molecules more readily than others. The cleavage reaction of fluid-phase and cell-bound C3b by soluble MCP and factor I produced iC3b, but no C3c and C3dg. These and prior data indicate that soluble MCP has potent cofactor activity for fluid-phase C3b or C3b bound to solubilized molecules, but acts inefficiently towards C3b on other cells. This functional profile is unique for a C3b/C4b binding protein and, taken together with its wide tissue distribution, suggests an important role for MCP in the regulation of the complement system.
Seya
T
T
Department of Immunology, Center for Adult Diseases, Osaka, Japan.
Atkinson
J P
JP
D000818:Animals; D015703:Antigens, CD; D018958:CD55 Antigens; D002460:Cell Line; D050577:Complement C3-C5 Convertases / Q000378:metabolism; D003169:Complement Inactivator Proteins / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D007700:Kinetics; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008970:Molecular Weight
D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D003169:Complement Inactivator Proteins; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D003165:Complement System Proteins; D050577:Complement C3-C5 Convertases