HUMAN SKELETAL MYOBLASTS SPONTANEOUSLY ACTIVATE ALLOGENEIC COMPLEMENTBUT ARE RESISTANT TO KILLING

The complement (C) system has previously been implicated in several di seases of muscle. We here report that human myoblasts or rhabdomyosarc oma cell lines spontaneously activate C through the classical pathway, causing release of anaphylatoxins and coating of myoblasts with opson ic C fragments but without causing cell killing. Survival of myoblasts is a consequence of the abundant expression of the membrane C regulat ory molecules MCP and CD59, and neutralization of CD59 renders cells s usceptible to C killing. The decay-accelerating factor was expressed a t a very low level. Myoblasts and rhabdomyosarcoma lines also abundant ly express the fluid-phase regulators C1-inhibitor, factor H, C4 bindi ng protein, S-protein, and clusterin and secrete a soluble form of CD5 9. Expression of membrane and fluid-phase regulators is enhanced by ei ther IFN-gamma or TNF-alpha. Although myoblasts resist C killing, spon taneous activation of C on these cells may have important consequences in inflammatory diseases of muscle where the generation of anaphylact ic and opsonic fragments will recruit and activate inflammatory cells. C activation on myoblasts may also have consequences for the use of t hese cells as vehicles for gene delivery. Inhibition of C using solubl e complement receptor 1 (sCR1) efficiently protected myoblasts from C attack in vitro, and this agent, already being tested in therapy of se veral C-mediated diseases, might be of value in inflammatory muscle di sease and in improving the efficiency of gene delivery.