EXPRESSION OF COMPLEMENT MEMBRANE REGULATORS MEMBRANE COFACTOR PROTEIN (CD46), DECAY-ACCELERATING FACTOR (CD55), AND PROTECTIN (CD59) IN HUMAN-MALIGNANT GLIOMAS
A. Maenpaa et al., EXPRESSION OF COMPLEMENT MEMBRANE REGULATORS MEMBRANE COFACTOR PROTEIN (CD46), DECAY-ACCELERATING FACTOR (CD55), AND PROTECTIN (CD59) IN HUMAN-MALIGNANT GLIOMAS, The American journal of pathology, 148(4), 1996, pp. 1139-1152
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.