C-protein in the skeletal muscle induces severe autoimmune polymyositis in Lewis rats.
To obtain a good animal model for polymyositis, we previously induced experimental autoimmune myositis (EAM) in Lewis rats by immunization with partially purified skeletal myosin. However, the nature of EAM-inducing antigen(s) in the partially purified myosin preparation remains unclear because it may contain several myositogenic antigens. In the present study, we further purified myosin and C-protein from partially purified myosin preparations and examined their EAM-inducing ability. It was revealed that immunization with both C-protein and purified myosin elicited EAM, which was essentially the same as that induced by partially purified myosin. However, their myositogenic ability was quite different. C-protein induced severe EAM of high histological grade and lesion frequency, whereas purified myosin induced only mild EAM. Immunohistochemical staining of C-protein-induced lesions demonstrated that muscle fiber-infiltrating cells were CD8beta+ T cells and macrophages and that CD4+ cells were mainly located in the endomysium and interfiber connective tissue. Collectively, these findings suggest that C-protein in the skeletal muscle is the major myositogenic antigen and induces inflammatory lesions mimicking those of human polymyositis.
Kohyama
K
K
Department of Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Japan.
Matsumoto
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D002352:Carrier Proteins / Q000276:immunology* / Q000302:isolation & purification; D000939:Epitopes; D006801:Humans; D007114:Immunization; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000276:immunology; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D009218:Myosins / Q000276:immunology / Q000302:isolation & purification; D017285:Polymyositis / Q000276:immunology* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D000099163:Myosin Binding Protein C
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D000939:Epitopes; D009218:Myosins; D000099163:Myosin Binding Protein C