Prolongation of rat cardiac allograft survival by a monoclonal antibody: anti-rat intercellular adhesion molecule-1.
A mouse monoclonal antibody 1A29, which binds to the rat intercellular adhesion molecule-1 (ICAM-1), was studied for its effect on cardiac allograft survival. Expression of ICAM-1 was detectable only on vascular endothelium in normal heart, but was induced on myocardium associated with interstitial mononuclear cell infiltration during acute rejection. Treatment with monoclonal antibody 1A29 for 10 days after transplantation in 15 rats significantly prolonged allograft survival (mean(s.d.) 18(2) days; P < 0.001), as compared with 15 isotype-matched control monoclonal antibody (mean(s.d.) 10(1) days) recipients. Five-day treatment with monoclonal antibody 1A29, when started at 5 days after transplantation (the time for which acute rejection is ongoing), also significantly extended the survival (mean(s.d.) 12(1) days; P < 0.01) in seven rats. On histological examination, treatment with monoclonal antibody 1A29 reduced the degree of T-cell infiltration of both CD4+ and CD8+ subsets, and greatly reduced myocardial necrosis, vascular injury and intravenous thrombi. These results indicate that an anti-ICAM-1 monoclonal antibody can be used to prevent or treat acute rejection in the rat cardiac allograft model and suggest that human ICAM-1 is an important target for immunosuppression in clinical organ transplantation.
Kobayashi
H
H
Department of Paediatric Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Miyano
T
T
Yamataka
A
A
Yamataka
T
T
Yagita
H
H
Eto
H
H
Ligo
Y
Y
Tansyo
S
S
Kojima
Y
Y
Tamatani
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D016516:CD4-CD8 Ratio; D015815:Cell Adhesion Molecules / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D018799:Intercellular Adhesion Molecule-1