IDENTIFICATION AND CHARACTERIZATION OF MEMBRANE COFACTOR PROTEIN (CD46) IN THE HUMAN KIDNEYS

Membrane cofactor protein (MCP, CD46) is an integral protein that serv es as a cofactor for factor I in inactivating C3b/C4b deposited on the same cell membrane as C3bi/C4c+C4d. This C3b/C4b inactivation is clos ely associated with self-protection of host cells from autologous comp lement attack. We have studied the distribution and properties of MCP in the normal human kidney by immunohistochemical and immunoblotting m ethods using monoclonal antibodies against MCP. MCP was predominantly expressed on the juxtaglomerular apparatus. Glomerular capillary walls , mesangial areas, and tubulus were also MCP positive. Glomerulus MCP was composed of two major bands of 45-65 kDa, which were similar to th ose of lymphocyte MCP: The proportion of the high and low molecular we ight components in glomerulus MCP, however, was considerably different from that of lymphocyte MCP among the individual samples tested. Glom erular epithelial cells and mesangial cells from an individual having equal amounts of high and low molecular weight components in the lymph ocytes were cultured seperately and the properties of their MCP invest igated. MCP in the mesangial cells and glomerular epithelial cells sho wed profiles in which the upper band was predominant. The results may explain the unique distribution of the high and low molecular weight f orms in the glomerulus. These forms of MCP together with factor I were all capable of inactivating C3b to C3bi. Message analysis suggested t hat glomerular epithelial cells and mesangial cells synthesized a sing le species of mRNA of 4.2 kb from which the polymorphic MCP species we re generated. Flow cytometric analysis suggested that MCP was minimal in mesangial cells. These results, taken together with the previous re ports on the distribution of other complement regulatory proteins, inf er that the distribution profile of MCP is rather similar to that of D AF but differs from those of CD59 and CR1 in the normal human kidney; this may reflect the differences between their roles or functional pro perties in renal tissue.