ICAM-1 and VCAM-1 in human renal allograft rejection

ICAM-1 and VCAM-1 in human renal allograft rejection. Light microscopy studies have demonstrated heightened ICAM-1 and VCAM-1 expression in renal allograft rejection in experimental animals and in humans, and administration of ICAM-1 blocking antibodies has been shown to prolong graft survival in nonhuman primates. We used a precise ultrastructural immunogold localization technique to identify the exact sites of expression of ICAM-1 and VCAM-1 in both normal human kidney and in renal allograft rejection. In the normal kidney ICAM-1 is moderately strongly expressed in glomeruli, on the endothelium and parietal epithelium and in the interstitium, on the endothelium of peritubular capillaries, arterioles and small arteries, on fibroblast-like interstitial cells and on the brush border of proximal tubules. In contrast, in normal kidney, VCAM-1 expression is restricted to the parietal epithelium and the basolateral surfaces of a few proximal tubule cells. In allograft rejection, although ICAM-1 expression appears to be increased, its pattern of distribution is similar to that seen in the normal kidney. However, VCAM-1 in allograft rejection is widely expressed on the endothelium of peritubular capillaries and arterioles in association with adhesion of mononuclear leukocytes within these vessels. The tubular expression of VCAM-1, although still focal in nature, is increased on the basolateral surfaces in association with lymphocytic infiltration of tubules. Although ICAM-1 expression appears to be up-regulated in renal allograft rejection in a pattern of distribution similar to that seen in the normal kidney, we postulate that it is VCAM-1 which appears on the peritubular capillary endothelium and is strongly focally expressed on the basolateral surfaces of tubules, which is perhaps more strategically placed to be the most relevant adhesion molecule in allograft rejection.