CHARACTERIZATION OF THE COMPLEMENT-REGULATORY PROTEINS DECAY-ACCELERATING FACTOR (DAF,CD55) AND MEMBRANE COFACTOR PROTEIN (MCP,CD46) ON A HUMAN COLONIC ADENOCARCINOMA CELL-LINE

To avoid destruction by complement, normal and malignant cells express membrane glycoproteins that restrict complement activity. These inclu de decay-accelerating factor (DAF, CD55), membrane cofactor protein (M CP, CD46) and protectin (CD59), which are all expressed on colonic ade nocarcinoma cells in situ. In this study we have characterised the C3/ C5 convertase regulators DAF and MCP on the human colonic adenocarcino ma cell line HT29. DAF was found to be a glycosyl-phosphatidylinositol -anchored 70-kDa glycoprotein. Blocking experiments with F(ab')2 fragm ents of the anti-DAF monoclonal antibody BRIC 216 showed that DAF modu lates the degree of C3 deposition and mediates resistance to complemen t-mediated killing of the cells. The expression and function of DAF we re enhanced by tumour necrosis factor alpha (TNF alpha) and interleuki n-1 beta (IL-1 beta). Cells incubated with interferon gamma (IFN gamma ) did not alter their DAF expression. Two MCP forms were expressed, wi th molecular masses of approximately 58 kDa and 68 kDa, the lower form predominating. MCP expression was up-regulated by IL-1 beta, but not by TNF alpha or IFN gamma. Expression of DAF and MCP promotes resistan ce of colonic adenocarcinoma cells to complement-mediated damage, and represents a possible mechanism of tumour escape.