EXPRESSION OF COMPLEMENT MEMBRANE REGULATORS MEMBRANE COFACTOR PROTEIN (CD46), DECAY-ACCELERATING FACTOR (CD55), AND PROTECTIN (CD59) IN HUMAN-MALIGNANT GLIOMAS

Gliomas are malignant brain tumors, which, despite recent progress in surgical and radiological treatment, still have a poor prognosis. sinc e gliomas apparently resist immunological clearance mechanisms, we bec ame interested in examining bow gliomas resist killing by the human co mplement system. The resistance of human cells to complement-mediated damage is, in large part, mediated by specific inhibitors of complemen t: membrane cofactor protein (CD46), decay-accelerating factor (CD55), and protectin (CD59). In the present study we examined the expression of complement regulators in 14 human glioma tumors and in 7 glioma ce ll lines (U251, U87, HS683, U373, U138, U118, and H2). Protectin was f ound to be strongly expressed by all glioma tumors and cell lines. Nor thern blotting analysis demonstrated the typical pattern of four to fi ve protectin mRNAs in the glioma cells. Except for blood vessels, the expression of decay-accelerating factor was weak or absent in the tumo rs in situ, whereas in the cell lines its expression varied ranging fr om negative to intermediate. Membrane cofactor protein was moderately expressed by all the cell lines but only weakly ia the tumors. Cell-ki lling experiments demonstrated that the glioma cell lines were excepti onally resistant to C-mediated lysis. Five of the seven cell lines (U3 73, HS683, U118, U138, and H2) resisted complement lysis under conditi ons where most other cell lines were sensitive to killing. Neutralizat ion experiments using specific monoclonal antibodies indicated that pr otectin was functionally the most important complement regulator in th e glioma cells. Tbe killing of the U87 and U251 cells could be signifi cantly increased by a blocking anti-protectin monoclonal antibody, whe reas for the other cell lines only moderate or no response was observe d. The H2 cell line resisted killing by all antibodies and by compleme nt These results show that protectin is the most important complement regulator on human glioma cells. The exceptional complement resistance of some glioma cell lines suggests that they may utilize other, hithe rto less well characterized, mechanisms to resist complement killing.