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 s hown to prolong graft survival in nonhuman primates. We used a precise ultrastructural immunogold localization technique to identify the exa ct sites of expression of ICAM-1 and VCAM-1 in both normal human kidne y and in renal allograft rejection. In the normal kidney ICAM-1 is mod erately strongly expressed in glomeruli, on the endothelium and pariet al epithelium and in the interstitium, on the endothelium of peritubul ar capillaries, arterioles and small arteries, on fibroblast-like inte rstitial cells and on the brush border of proximal tubules. In contras t, in normal kidney, VCAM-1 expression is restricted to the parietal e pithelium and the basolateral surfaces of a few proximal tubule cells. In allograft rejection, although ICAM-1 expression appears to be incr eased, its pattern of distribution is similar to that seen in the norm al kidney. However, VCAM-1 in allograft rejection is widely expressed on the endothelium of peritubular capillaries and arterioles in associ ation with adhesion of mononuclear leukocytes within these vessels. Th e tubular expression of VCAM-1, although still focal in nature, is inc reased on the basolateral surfaces in association with lymphocytic inf iltration of tubules. Although ICAM-1 expression appears to be up-regu lated in renal allograft rejection in a pattern of distribution simila r to that seen in the normal kidney, we postulate that it is VCAM-1 wh ich appears on the peritubular capillary endothelium and is strongly f ocally expressed on the basolateral surfaces of tubules, which is perh aps more strategically placed to be the most relevant adhesion molecul e in allograft rejection.