Membrane cofactor protein (CD46) protects cells from complement-mediated attack by an intrinsic mechanism.
The cleavage of C3 is a critical step for complement (C) activation in the classical and alternative pathways. This reaction is controlled by the regulators of C activation protein family. Membrane cofactor protein (MCP) is a cofactor for the factor I-mediated inactivation of C3b and C4b. As a widely distributed membrane protein, MCP may protect host cells from inadvertent C activation. Human MCP has recently been shown to protect transfected rodent cells from human C-mediated lysis. In this report the relationship of MCP expression to C3b deposition and cytoprotection was examined using NIH/3T3 cells transfected with human MCP and exposed to human serum as a source of C and naturally occurring anti-mouse antibody. MCP inhibited C3b deposition in a dose-dependent fashion and inhibited lysis of the mouse cells expressing it. MCP did not inhibit lysis on bystander cells. These results demonstrate the protective role of MCP, at the cellular level, by an intrinsic mechanism.
Oglesby
T J
TJ
Division of Rheumatology, Howard Hughes Medical Institute, St. Louis, Missouri.
Allen
C J
CJ
Liszewski
M K
MK
White
D J
DJ
Atkinson
J P
JP
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D003176:Complement C3 / Q000378:metabolism; D003165:Complement System Proteins / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D014162:Transfection
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C497857:CD46 protein, human; D003176:Complement C3; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D003165:Complement System Proteins; D004247:DNA