Analysis of inflammatory endothelial changes, including VCAM-1 expression, in murine cardiac grafts.
We have employed a murine model of cardiac transplantation and two monoclonal antibodies, M/K-2 and MECA-32, to study the responses of graft endothelia during allograft rejection. Using immunohistologic techniques, we demonstrate that the monoclonal antibody M/K-2, which binds to the murine cellular adhesion molecule VCAM-1, reacts with an inducible endothelial epitope found in rejecting cardiac allografts, but not in cardiac isografts, normal cardiac tissues, or extracardiac vasculature from allografted mice. Similar, but focal, M/K-2 reactivity is also found in nontransplanted hearts undergoing virally induced myocarditis. M/K-2 reactivity does not develop in the nonrejecting cardiac allografts from nu/nu mice, and M/K-2 reactivity is found only in grafts that develop CD25+ graft-infiltrating cells--i.e., allografts but not isografts. PCR analyses of grafts during development of VCAM-1 expression indicate that allografts, but not isografts, contain mRNA for the cytokines IL-2 and IFN-gamma, and either of these cytokines may be associated with the expression of M/K-2 reactivity in rejecting allografts. Unlike M/K-2, MECA-32 identifies an inducible epitope that is observed on myocardial endothelia of both isografts and allografts, but not normal cardiac tissues. Further, expression of the MECA-32 epitope can occur in grafts that do not develop CD25+ infiltrating lymphocytes, since it is observed in isografts and the native hearts of transplanted or sham-operated mice. Indeed, MECA-32 reactivity may be T cell independent, since it is also found in nonrejecting allografts of nu/nu mice. PCR analyses of grafts during development of MECA-32 reactivity indicate that cardiac isografts contain mRNA for IL-1, IL-6, TNF, and lymphotoxin. One or more of these might be associated with induction of MECA-32 reactivity.
Pelletier
R P
RP
Department of Surgery, Ohio State University College of Medicine, Columbus 43210.
Morgan
C J
CJ
Sedmak
D D
DD
Miyake
K
K
Kincade
P W
PW
Ferguson
R M
RM
Orosz
C G
CG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation; D007249:Inflammation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D014184:Transplantation, Homologous; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019010:Vascular Cell Adhesion Molecule-1