Strain combination-dependent genesis of necrotizing arteritis in anti-ICAM-1 antibody-perfused renal allografts in the rat.
Rat kidneys were perfused with anti-intercellular adhesion molecule-1 (anti-ICAM-1) monoclonal antibody prior to allotransplantation. In the two strain combinations examined, LEF-to-WKAH transplants resulted in accelerated graft loss, and no prolongation of graft survival. The accelerated graft loss was the result of frequent occurrence of necrotizing arteritis within the grafts. In contrast, TO-to-WKAH transplants resulted in no change in graft survival and no arteritis. Necrotizing vasculitis in the LEJ-to-WKAH grafts was characterized by fibrinoid necrosis, collection of cellular infiltrates and serum macromolecular protein entrapment. The F(ab1)2 form of anti-ICAM-1 antibody partially preserved the antibody's capacity to accelerate graft loss. Therefore, although endothelial injury by Fc-mediated cytotoxicity may be involved in vascular damage, other mechanisms also come into play. The amount and distribution pattern of ICAM-1 antigen were identical in both TO and LEJ strains. Intravenous anti-ICAM-1 antibody administration combined with lipopolysaccharide, Poly(I)-Poly(C), warm ischemia to the kidney, or subcutaneous immunization with allogeneic spleen cells, but without renal transplantation, did not generate necrotizing vasculitis or proteinuria. These observations plus our previous data on the rat liver transplantation model clearly show that graft perfusion with anti-ICAM-1 monoclonal antibody invokes extensive vascular damage within allografts by Fc-mediated and Fc-independent mechanisms, depending on the donor-to-host combination.
Kanagawa
K
K
Department of Pathology, Hokkaido University, School of Medicine, Sapporo, Japan.
Ishikura
H
H
Ishizu
A
A
Kimura
C
C
Seki
T
T
Koyanagi
T
T
Yoshiki
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015153:Blotting, Western; D003602:Cytotoxicity, Immunologic; D006085:Graft Survival; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000276:immunology*; D007668:Kidney / Q000098:blood supply*; D016030:Kidney Transplantation; D010488:Polyarteritis Nodosa / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1