Pathogenic mechanisms in rheumatic carditis: focus on valvular endothelium.
To clarify immune-mediated mechanisms in rheumatic heart disease caused by group A streptococcal infection, valve tissues from rheumatic patients with valvular heart disease who required valve replacement were studied for reactivity with monoclonal anti-CD4 or anti-CD8 monoclonal antibodies or anti-vascular cell adhesion molecule-1 (VCAM-1). At the valve surface, CD4(+) and CD8(+) T lymphocytes were adherent to valve endothelium and penetrated through the subendothelial layer. T cell extravasation into the valve through the surface valvular endothelium appeared to be an important event in the development of rheumatic heart disease. VCAM-1 was expressed on the valvular endothelium in rheumatic valves. Evidence suggested that the pathogenesis of rheumatic heart disease involved the activation of surface valvular endothelium with the expression of VCAM-1 and the extravasation of CD4(+) and CD8(+) lymphocytes through the activated endothelium into the valve. Lymphocytic infiltration through the valve surface endothelium has not been appreciated as a potential initiating step in disease pathogenesis.
Roberts
S
S
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Kosanke
S
S
Terrence Dunn S
Jankelow
D
D
Duran
C M
CM
Cunningham
M W
MW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002448:Cell Adhesion; D002648:Child; D004699:Endocardium / Q000276:immunology*; D004727:Endothelium / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve / Q000276:immunology* / Q000503:physiopathology; D009205:Myocarditis / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D012214:Rheumatic Heart Disease / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D013297:Streptococcus pyogenes; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D019010:Vascular Cell Adhesion Molecule-1