I. Nakanishi et al., IDENTIFICATION AND CHARACTERIZATION OF MEMBRANE COFACTOR PROTEIN (CD46) IN THE HUMAN KIDNEYS, European Journal of Immunology, 24(7), 1994, pp. 1529-1535
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.