Leukocyte CD18 receptors may be a better target than ICAM-1 ligands for reducing histologic evidence of cellular and vascular rejection in the rabbit.
Building evidence suggests that blocking the ICAM-1/CD18 interaction may affect the course of graft rejection. Treatment with monoclonal antibody (mAb) to CD18 was compared to antibody to ICAM-1 in a rabbit heterotopic heart transplant model to determine whether blocking the leukocyte receptor for ICAM-1, CD18, was more effective than antibody targeting of the ligand for ICAM-1. Following transplantation, 28 recipient rabbits were randomized to receive either placebo, mAb to CD18, or mAb to ICAM-1 for 7 days until sacrifice. The cellular rejection grade and percentage of arteries with vascular rejection were significantly lower in animals treated with anti-CD18 than with anti-ICAM-1. As assessed by histology, antibody treatment was more effective in reducing both cellular and vascular rejection when directed at the leukocyte receptor CD18 than the ICAM-1 ligand. These findings suggest that other ICAM ligands may play an active role in the immune response and that CD18 may be important for migration of lymphocytes through myocardium.
Sadahiro
M
M
Department of Cardiovascular Surgery, Tohoku University, Sendai, Japan.
McDonald
T O
TO
Nelson
K
K
Thomas
R
R
Allen
M D
MD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001665:Binding Sites; D018821:CD18 Antigens / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D007958:Leukocyte Count; D011817:Rabbits
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D018799:Intercellular Adhesion Molecule-1