LPS promotes CB3-induced myocarditis in resistant B10.A mice.
Coxsackie virus B3 (CB3) infection of A/J or A.SW mice results in autoimmune myocarditis characterized by a diffuse mononuclear cell infiltrate and heart-specific autoantibodies. C57BL/10 congenic mice that are identically treated are resistant to this disease. CB3-infected resistant B10.A mice were treated with LPS to determine if this immunomodulator alters disease susceptibility. In contrast to mice infected only with CB3 or treated only with LPS. CB3-infected/LPS-treated (CB3/LPS) B10.A mice developed autoimmune myocarditis similar to that observed in susceptible A/J or A.SW mice. By Day 14, CB3/LPS-induced disease was characterized by significant mortality, myocardial immunoglobulin deposition, and mononuclear cell infiltration of the heart. Immunohistochemical examination revealed deposits of IgG in the heart tissue and serum IgG autoantibodies reactive with sarcolemmal and fibrillary antigens in normal heart tissue. This serum IgG reacted with normal mouse cardiac antigens of a wide range of molecular weights by Western immunoblotting. Because LPS treatment is capable of increasing cytokine levels as well as MHC Class I and Class II expression in heart tissue, it suggests that these factors may contribute to susceptibility to autoimmune myocarditis in CB3-infected mice.
Lane
J R
JR
Johns Hopkins University, School of Hygiene and Public Health, Department of Immunology and Infectious Diseases, Baltimore, Maryland 21205.
Neumann
D A
DA
Lafond-Walker
A
A
Herskowitz
A
A
Rose
N R
NR
D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D003384:Coxsackievirus Infections / Q000150:complications*; D029822:Enterovirus B, Human; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D009206:Myocardium / Q000276:immunology / Q000473:pathology
D001323:Autoantibodies; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D008070:Lipopolysaccharides