Cardiac myosin-induced myocarditis. Heart autoantibodies are not involved in the induction of the disease.
We recently demonstrated that cardiac myosin is capable of inducing autoimmune myocarditis in genetically predisposed mice. This disease parallels coxsackievirus B3-induced autoimmune myocarditis in many respects and is associated with high-titer autoantibodies specific for cardiac myosin. The following lines of evidence suggest that these autoantibodies are not involved in the induction of autoimmune myocarditis: 1) immunoperoxidase staining of heart sections from cardiac myosin-immunized A/J and A.SW mice revealed IgG depositions only along damaged muscle fibres in infiltrated areas, but not in intact tissue; 2) myosin autoantibodies did not bind to the surface of viable cardiac myocytes isolated from mice, but only reacted with myocytes permeabilized with detergent; 3) mice treated with a single high dose of cyclophosphamide, which reduces the humoral immune response, still developed severe myocarditis, despite the fact that their autoantibody titers were reduced to the level of adjuvant-injected controls; and 4) passive transfer of high-titer myosin autoantibodies failed to induce myocarditis, although the titers in the recipients were comparable to those found in mice with cardiac myosin-induced disease. Together, the results suggest that high-titer myosin autoantibodies are secondary rather than primary to the disease.
Neu
N
N
Institute for General and Experimental Pathology, Medical School, University of Innsbruck, Austria.
Ploier
B
B
Ofner
C
C
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000954:Antigens, Surface / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D003520:Cyclophosphamide / Q000494:pharmacology; D007116:Immunization, Passive; D007136:Immunoglobulins / Q000378:metabolism; D051379:Mice; D008805:Mice, Inbred A; D009205:Myocarditis / Q000276:immunology*; D009206:Myocardium / Q000276:immunology*; D009218:Myosins / Q000276:immunology*
D000954:Antigens, Surface; D001323:Autoantibodies; D007136:Immunoglobulins; D003520:Cyclophosphamide; D009218:Myosins