title: Cooperation between decay-accelerating factor and membrane cofactor protein in protecting cells from autologous complement attack.
abstract: Decay-accelerating factor (DAF or CD55) and membrane cofactor protein (MCP or CD46) function intrinsically in the membranes of self cells to prevent activation of autologous complement on their surfaces. How these two regulatory proteins cooperate on self-cell surfaces to inhibit autologous complement attack is unknown. In this study, a GPI-anchored form of MCP was generated. The ability of this recombinant protein and that of naturally GPI-anchored DAF to incorporate into cell membranes then was exploited to examine the combined functions of DAF and MCP in regulating complement intermediates assembled from purified alternative pathway components on rabbit erythrocytes. Quantitative studies with complement-coated rabbit erythrocyte intermediates constituted with each protein individually or the two proteins together demonstrated that DAF and MCP synergize the actions of each other in preventing C3b deposition on the cell surface. Further analyses showed that MCP's ability to catalyze the factor I-mediated cleavage of cell-bound C3b is inhibited in the presence of factors B and D and is restored when DAF is incorporated into the cells. Thus, the activities of DAF and MCP, when present together, are greater than the sum of the two proteins individually, and DAF is required for MCP to catalyze the cleavage of cell-bound C3b in the presence of excess factors B and D. These data are relevant to xenotransplantation, pharmacological inhibition of complement in inflammatory diseases, and evasion of tumor cells from humoral immune responses.
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: W G
authors.initials: WG
authors.lastname: Brodbeck
authors.forename: C
authors.initials: C
authors.lastname: Mold
authors.forename: J P
authors.initials: JP
authors.lastname: Atkinson
authors.forename: M E
authors.initials: ME
authors.lastname: Medof
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018958:CD55 Antigens / Q000502:physiology*; D016466:CHO Cells; D051561:Complement C3 Convertase, Alternative Pathway; D050577:Complement C3-C5 Convertases; D003179:Complement C3b / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D003180:Complement C3b Inactivator Proteins / Q000502:physiology*; D011415:Complement Factor B / Q000502:physiology; D003170:Complement Pathway, Alternative / Q000276:immunology*; D006224:Cricetinae; D004357:Drug Synergism; D017261:Glycosylphosphatidylinositols / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010446:Peptide Fragments / Q000502:physiology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D003180:Complement C3b Inactivator Proteins; D017261:Glycosylphosphatidylinositols; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D003179:Complement C3b; D050577:Complement C3-C5 Convertases; D051561:Complement C3 Convertase, Alternative Pathway; D011415:Complement Factor B