In Vivo Effects of Monoclonal Antibodies against Rat β2 Integrins on Kidney Ischemia–Reperfusion Injury

Abstract Background. Ischemia–reperfusion (IR) involves adhesion of leukocytes to the activated endothelium, leading to tissue damage. CD11/CD18 β 2 integrins interact with their ligands on endothelial cells and may therefore represent a therapeutic target for the prevention of IR. We investigated the effects of three monoclonal antibodies (mAbs) that recognize epitopes of heavy or light chain of the β 2 integrins on IR in kidneys. Methods. Uninephrectomized Fischer rats were subjected to 45 or 60 min of renal ischemia, treated with intravenously anti-β 2 integrin monoclonal antibodies (anti-CD11a, anti-CD11b, and anti-CD18) 5 min prior to reperfusion, and compared to a nontreated group. Serum creatinine, blood urea nitrogen (BUN), and kidney histopathological damages were assessed at 1, 2, and 7 days after ischemia. Results. After 45 and 60 min of ischemia, serum creatinine and BUN were significantly higher in the control than in animals treated with anti-CD11a and anti-CD18 at 24 and 48 h. Administration of anti-CD11b had a beneficial effect on renal function after 45 min but not after 60 min of ischemia. Histologic and immunostaining studies demonstrated mild tubular necrosis and less leukocyte infiltration in the anti-CD11a- and anti-CD18-treated groups compared to the control group. Conclusion. These results indicate that selected antibodies to CD11a/CD18 may decrease kidney IR injury when administered prior to reperfusion.