In vivo deposition of myosin-specific autoantibodies in the hearts of mice with experimental autoimmune myocarditis.
Experimental autoimmune myocarditis (EAM) is elicited in certain strains of mice by immunizing with mouse cardiac myosin. Concomitant with the onset of myocardial inflammation is the induction of circulating IgG antibodies to myosin. To further examine the role of myosin in disease, both EAM-susceptible (A/J) and EAM-resistant (B10.A) mice were immunized with myosin emulsified in CFA and examined for myocardial inflammation and IgG deposition. Myocarditis was common in susceptible, but not resistant strain mice. IgG deposition was extensive in A/J mice, but modest in B10.A mice, when compared to controls given adjuvant alone. Localization was independent of inflammatory or necrotic lesions. A spot ELISA indicated that antimyosin IgG antibody-secreting cells were present in the myocardial infiltrate and likely contributed to antibody localization. Antibody was eluted from the hearts of immunized animals and found to react strongly with normal heart tissue by indirect immunohistochemistry. This reactivity was not completely absorbed by skeletal muscle, indicating that some of the antibody was heart-specific. Western immunostaining demonstrated that eluates from immunized A/J and B10.A mice possessed anti-myosin antibody activity; similar reactivity was not observed in eluates from control mice of either strain. Comparison of heart reactivity with syngeneic and allogeneic tissue suggests that although myosin immunization elicits homologous antibody in both strains, each may recognize distinct epitopes. These findings strongly suggest that cardiac myosin or a myosin-like determinant is expressed on the surface of normal mouse myocytes.
Neumann
D A
DA
Johns Hopkins University, School of Hygiene and Public Health, Department of Immunology and Infectious Diseases Baltimore, MD 21205.
Lane
J R
JR
Wulff
S M
SM
Allen
G S
GS
LaFond-Walker
A
A
Herskowitz
A
A
Rose
N R
NR
D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology; D001323:Autoantibodies / Q000378:metabolism*; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D007074:Immunoglobulin G / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009205:Myocarditis / Q000276:immunology*; D009206:Myocardium / Q000276:immunology; D009218:Myosins / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D009218:Myosins