title: Pathogenic mechanisms in rheumatic carditis: focus on valvular endothelium.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: S
authors.initials: S
authors.lastname: Roberts
authors.forename: S
authors.initials: S
authors.lastname: Kosanke
authors.lastname: Terrence Dunn S
authors.forename: D
authors.initials: D
authors.lastname: Jankelow
authors.forename: C M
authors.initials: CM
authors.lastname: Duran
authors.forename: M W
authors.initials: MW
authors.lastname: Cunningham
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D019010:Vascular Cell Adhesion Molecule-1