Reduction in cellular and vascular rejection by blocking leukocyte adhesion molecule receptors.
Whether antibody blockage of leukocyte receptors for intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 would prevent cardiac graft rejection was studied in a rabbit heterotopic transplant model. Monoclonal antibody 60.3, anti-CD18 (intercellular adhesion molecule-1 receptor, Group 1, n = 10) and monoclonal antibody HP1/2, anti-VLA-alpha 4 (vascular cell adhesion molecule-1 receptor, Group 2, n = 10) were administered to transplanted unimmunosuppressed animals. At 7 days, donor heart histology was compared to transplanted untreated controls (Group 3, n = 11). Peripheral white blood cell counts on postoperative day 2 were significantly higher in both treatment groups than controls. Significant increases in circulating neutrophils occurred in Group 1 (P < or = 0.05); lymphocytes predominated in Group 2 (P < or = 0.05). A significant reduction in cellular rejection was seen in Group 1 (P < or = 0.05) but not Group 2 hearts. Group 1 hearts demonstrated localization of lymphocytes to perivenular collections, whereas Group 2 hearts evidenced diffuse interstitial infiltration. Both treatment groups demonstrated a reduction in transplant arteritis compared to controls. Results suggest that monoclonal antibody 60.3 (anti-CD18) may hold promise as a therapeutic agent for both cellular and vascular rejection. Monoclonal antibody HP1/2 (anti-VLA-alpha 4) may reduce vascular rejection disproportionate to cellular rejection.
Sadahiro
M
M
Department of Surgery, University of Washington, Seattle.
McDonald
T O
TO
Allen
M D
MD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology; D001167:Arteritis / Q000473:pathology; D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules / Q000276:immunology; D003331:Coronary Vessels / Q000473:pathology; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation; D018799:Intercellular Adhesion Molecule-1; D007958:Leukocyte Count; D008214:Lymphocytes / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D011817:Rabbits; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology*; D016029:Receptors, Very Late Antigen / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016028:Receptors, Leukocyte-Adhesion; D016029:Receptors, Very Late Antigen; D018799:Intercellular Adhesion Molecule-1