Human skeletal myoblasts spontaneously activate allogeneic complement but are resistant to killing
Gasque, P.; Morgan, B.P.; Legoedec, J.; Chan, P.; Fontaine, M.
Journal of Immunology 156(9): 3402-3411
1996
ISSN/ISBN: 0022-1767 PMID: 8617966 Document Number: 457518
The complement (C) system has previously been implicated in several diseases of muscle. We here report that human myoblasts or rhabdomyosarcoma cell lines spontaneously activate C through the classical pathway, causing release of anaphylatoxins and coating of myoblasts with opsonic C fragments but without causing cell killing. Survival of myoblasts is a consequence of the abundant expression of the membrane C regulatory molecules MCP and CD59, and neutralization of CD59 renders cells susceptible to C killing. The decay-accelerating factor was expressed at a very low level. Myoblasts and rhabdomyosarcoma lines also abundantly express the fluid-phase regulators C1-inhibitor, factor H, C4 binding protein, S-protein, and clusterin and secrete a soluble form of CD59. Expression of membrane and fluid-phase regulators is enhanced by either IFN-gamma or TNF-alpha. Although myoblasts resist C killing, spontaneous activation of C on these cells may have important consequences in inflammatory diseases of muscle where the generation of anaphylactic and opsonic fragments will recruit and activate inflammatory cells. C activation on myoblasts may also have consequences for the use of these cells as vehicles for gene delivery. Inhibition of C using soluble complement receptor 1 (sCR1) efficiently protected myoblasts from C attack in vitro, and this agent, already being tested in therapy of several C-mediated diseases, might be of value in inflammatory muscle disease and in improving the efficiency of gene delivery.