Membrane cofactor protein (MCP) is a cell-associated regulatory molecule for C system with C3b/C4b binding and factor I-dependent cofactor activity. mAb were raised against MCP and amounts and distribution examined on normal human cells and cell lines. The mean quantity of MCP was 3000 to 7000 copies/cell in normal blood cells, except for E which have no MCP. 

Of note, PMN did not fully reveal all MCP sites until incubated for greater than 30 min at 37° C. In most tumor cell lines, except for B cell lineages, expression of MCP increased by 2- to 8-fold in comparison with the normal cell counterparts. 

Strikingly, recombinant granulocyte CSF treatment of myeloid cell lines and hemin treatment of an erythroblastoid cell line, K562, led to a decrease of MCP to near normal levels. In contrast, C3b/C4b receptor (CR1) tended to increase with granulocyte-CSF treatment in several cell lines. We simultaneously determined levels of decay-accelerating factor (DAF) and CR1 in these tumor cells, and tested susceptibility to C3 deposition via activation of the alternative C pathway. 

Of 21 cell lines we examined, 14 lacked CR1 and two lacked DAF; none, however, lacked MCP. A slight amount of C3 deposition was observed in some myeloid cell lines and EBV-infected B cell lines. However, C3 deposition did not reflect a defect in the regulatory proteins. 

Tumor cells bearing MCP, lacking CR1 or DAF, and undergoing no C3 deposition, may escape C attack due to the compensatory effect of MCP in the absence of the other regulatory proteins. High expression of MCP provides a convenient means for tumor cells to blockC attack and survive in blood stream. 

We favor the interpretation that MCP is up-regulated in association with certain malignant disorders, and that cell differentiation results in a switch from an MCP-dominant state to aCR1-dominant state.