[Monoclonal antibody against LFA-1 (CD18) inhibits cellular and vascular rejection in rabbit cardiac allografts].
Leukocyte binding to endothelial adhesion molecules has been said to be an initiating step in cardiac allograft rejection. Whether antibody blockage of leukocyte ligands, CD18, for intercellular adhesion molecule (ICAM-1) would prevent allograft rejection was studied in a rabbit heterotopic transplant model. Cervical cardiac transplant was performed between donor Staffland and New Zealand White recipient rabbits. Ten animals were treated with intravenous anti-CD8 monoclonal antibody, 60.3, at the dose of 1 mg/kg for 7 days. No immunosuppressive drugs were used. Eleven transplant controls were untreated. At 7 days, animals were sacrificed and donor heart histology was compared. Peripheral WBC counts were significantly higher in treatment group compared to untreated group on both postoperative day 2 and 7. The cellular rejection score was 30% lower in treated group than untreated (p < 0.05), demonstrating localization of lymphocytes to perivenular collections. The proportion of arteries with evidence of vasculitis was 45% lower in treated group. Results suggests that monoclonal antibody against LFA-1 (CD18) may hold promise as a therapeutic agent for both cellular and vascular rejection.
Department of Thoracic and Cardiovascular Surgery, Tohoku University School of Medicine, Sendai, Japan.
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Sadahiro
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Allen
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D006084:Graft Rejection; D016027:Heart Transplantation / Q000276:immunology*; D007111:Immunity, Cellular; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D009206:Myocardium / Q000473:pathology; D011817:Rabbits; D016042:Transplantation, Heterotopic / Q000276:immunology*; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1