title: Human skeletal myoblasts spontaneously activate allogeneic complement but are resistant to killing.
abstract: 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 I (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.
authors.affiliation: Department of Medical Biochemistry, University of Wales College of Medicine, Cardiff, United Kingdom.
authors.forename: P
authors.initials: P
authors.lastname: Gasque
authors.forename: B P
authors.initials: BP
authors.lastname: Morgan
authors.forename: J
authors.initials: J
authors.lastname: Legoedec
authors.forename: P
authors.initials: P
authors.lastname: Chan
authors.forename: M
authors.initials: M
authors.lastname: Fontaine
mesh_terms: D016923:Cell Death / Q000276:immunology; D002478:Cells, Cultured; D003169:Complement Inactivator Proteins / Q000096:biosynthesis / Q000235:genetics; D003171:Complement Pathway, Classical / Q000235:genetics*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D018482:Muscle, Skeletal / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000302:isolation & purification; D017463:Receptors, Complement 3b / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D012208:Rhabdomyosarcoma / Q000235:genetics / Q000276:immunology; D012995:Solubility; D014407:Tumor Cells, Cultured
chemical_list: D003169:Complement Inactivator Proteins; D012333:RNA, Messenger; D017463:Receptors, Complement 3b; D011994:Recombinant Proteins