Distribution of cell adhesion molecules (ICAM-1, VCAM-1, ELAM-1) in renal tissue during allograft rejection.

The tissue distribution of cellular adhesion molecules (CAMs) was studied in specimens from 10 normal human kidneys and in 52 biopsies from kidney allografts with cell-mediated rejection. In addition to the vascular presence of ICAM-1, a common finding in normal kidneys, expression of ICAM-1 on tubular cells was observed in 22 graft biopsies. Compared with normal kidneys, where VCAM-1 was present on Bowman's capsules and few proximal tubular cells, a markedly enhanced expression of VCAM-1 in numerous tubuli (including distal tubular segments) was observed in 51 graft biopsies. In 41 graft specimens VCAM-1 appeared also in variable numbers of peritubular capillaries. Infiltrating leukocytes carrying VCAM-1 were observed in 7 grafts. ELAM-1 could not be found in normal kidneys but was restricted to some peritubular capillaries in 29 grafts. Comparable results were obtained with cultured renal tubular cells when stimulated by TNF-alpha. That the induced appearance of adhesion molecules was in fact related to actual cellular synthesis was demonstrated by Northern blot analysis. Thus, little ICAM-1 specific mRNA of 3.4-kb length could be detected in unstimulated cultured renal tubular cells, but hybridization was markedly increased after stimulation with TNF-alpha. A substantial amount of VCAM-1 specific mRNA of 3.2-kb length was present already in unstimulated renal tubular cells. Likewise, synthesis of VCAM-1 mRNA was enhanced by stimulation with TNF-alpha. TNF-stimulated endothelial cells also showed weak synthesis of VCAM-1 mRNA. The results provide further evidence that constitutive and inducible expression of cell adhesion molecules contributes to the process of allograft rejection.