Treatment with anti-vascular cell adhesion molecule 1 monoclonal antibody induces long-term murine cardiac allograft acceptance.
Daily in vivo treatment of murine H-2d --> H-2b cardiac allograft recipients with 400 micrograms/day i.p. of M/K-2, a mAb to the endothelial adhesion molecule VCAM-1, resulted in prolongation of graft survival. The surviving allografts showed little of the histologic changes observed in acutely rejecting control allografts. When antibody treatment was discontinued after 20 days, grafts continued to function for at least 40 more days. This was approximately 30 days after mAb was no longer detectable by ELISA in the circulation, or by immunoperoxidase staining at the graft site. The most notable feature of grafts that survived 60 days was the presence of mild interstitial fibrosis. Endothelial reactivity was minimal with the mAbs MECA-32 and M/K-2, which have been used in previous studies to visualize the extensive endothelial inflammation that develops during untreated acute rejection. There was a mild cellular infiltrate containing T cells, but few macrophages. However, infiltrating T cells appeared to be inactive in that IL-2R+ cells were immunohistologically undetectable and mRNA for IL-2, IL-4, or IFN-gamma was undetectable by polymerase chain reaction. In general, the immunologic conditions in these long-term grafts differed from those seen in normal cardiac tissue, cardiac isografts, or cardiac allografts. These data demonstrate that M/K-2 mAb can suppress cardiac allograft rejection and induce long-term graft acceptance. This graft survival appears to be associated with the development of a unique state of immunity at the graft site.
Orosz
C G
CG
Department of Surgery, Ohio State University, College of Medicine, Columbus 43210.
Ohye
R G
RG
Pelletier
R P
RP
Van Buskirk
A M
AM
Huang
E
E
Morgan
C
C
Kincade
P W
PW
Ferguson
R M
RM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D016207:Cytokines / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D004801:Eosine Yellowish-(YS); D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation; D006416:Hematoxylin; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000166:cytology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013194:Staining and Labeling / Q000379:methods; D014184:Transplantation, Homologous; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016207:Cytokines; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin