Induction of myocarditis and valvulitis in lewis rats by different epitopes of cardiac myosin and its implications in rheumatic carditis.
Immune responses against cardiac myosin and group A streptococcal M protein have been implicated in the pathogenesis of rheumatic heart disease. Although cardiac myosin is known to produce myocarditis in susceptible animals, it has never been investigated for its role in production of valvular heart disease, the most serious sequelae of group A streptococcal infection in acute rheumatic fever. In our study, cardiac myosin induced valvulitis in the Lewis rat, and epitopes responsible for production of valvulitis were located in the rod region. Human and rat cardiac myosins induced severe myocarditis in the Lewis rats as expected. A purified S2 fragment (amino acid sequences 842 to 1295) produced the most severe myocarditis as well as valvulitis. Different regions of light meromyosin produced valvulitis (residues 1685 to 1936) or myocarditis (residues 1529 to 1611). Because streptococcal M proteins produced valvular heart disease in Lewis rats and have been linked to anti-cardiac myosin responses, we reacted myosin-sensitized lymphocytes isolated from the hearts of Lewis rats with peptides of streptococcal M5 protein in tritiated thymidine assays. Infiltrating lymphocytes responded most strongly to peptides within the B repeat region of streptococcal M protein. These data show direct evidence that immune responses against cardiac myosin lead to valvular heart disease and the infiltration of the heart by streptococcal M protein reactive T lymphocytes.
Galvin
Jeffrey E
JE
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
Hemric
Mark E
ME
Kosanke
Stanley D
SD
Factor
Stephen M
SM
Quinn
Anthony
A
Cunningham
Madeleine W
MW
D000818:Animals; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D000939:Epitopes / Q000276:immunology*; D006349:Heart Valve Diseases / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000473:pathology; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D015879:Myosin Subfragments / Q000276:immunology; D009218:Myosins / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012214:Rheumatic Heart Disease / Q000276:immunology
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D000939:Epitopes; D015879:Myosin Subfragments; D010446:Peptide Fragments; C014689:streptococcal M protein; D009218:Myosins