Expression of adhesion molecules in kidney with experimental chronic obstructive uropathy: The pathogenic role of ICAM-1 and VCAM-1

Background: Chronic obstructive uropathy induced by maintained unilateral u reter ligation in the rat is characterized morphologically by interstitial inflammation, interstitial fibrosis, and tubular atrophy. Infiltrating mono nuclear inflammatory cells, particularly T lymphocytes and macrophages, may contribute to the progression of this lesion by mediating tubular injury a nd by the activation of interstitial fibroblasts, with resultant tubular at rophy and interstitial fibrosis, respectively. Altered expression and activ ation of adhesion molecules by leukocytes, vascular endothelial cells, and parenchymal cells likely contributes both to the infiltration of inflammato ry cells into the tubulointerstitial compartment and to the interaction of activated inflammatory cells with parenchymal cells. Methods: In the curren t study, we examined changes in the expression of intercellular adhesion mo lecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in a 90-da y model of maintained unilateral ureter ligation in male Sprague-Dawley rat s. Results: Rat kidneys showed constitutive expression of ICAM-1 mRNA and c onstitutive immunostaining for ICAM-1 in peritubular capillaries, glomeruli , and a small percentage of cortical tubules. Ureter ligation resulted in a rapid increase in ICAM-1 mRNA, which was almost 2-fold greater than those of the contralateral and control kidneys as early as 3 h and which was main tained at a 4- to 6-fold higher level in the ligated vs. contralateral kidn eys throughout the entire 90-day time course. There was a marked increase i n ICAM-1 immunostaining within the tubular epithelium, with up to 80% of bo th cortical and medullary tubular cross-sections showing strong apical immu nostaining from day 6 to 25, with a subsequent decrease throughout the rema inder of the experiment. ICAM-1 immunostaining in the expanding interstitiu m in the ligated kidneys showed a gradual increase throughout the duration of the experiment. In contrast, glomerular immunostaining for ICAM-1 was de creased in the ligated compared to the contralateral kidneys throughout the entire experiment. There was a later but prominent increase in VCAM-1 mRNA in ligated kidneys, which was first evident at 2 days and which was mainta ined 2- to 10-fold greater than the contralateral kidneys throughout the en tire time course. VCAM-1 immunostaining increased in the expanding intersti tium, but decreased in glomeruli in obstructed vs, contralateral kidneys. T ubular staining for VCAM-1 did not change after ureter ligation. Conclusion : Increased ICAM-1 and VCAM-1 may contribute to the prominent inflammatory cell infiltration in the chronic tubulointerstitial nephritis accompanying maintained unilateral ligation. Tubule expression of ICAM-1, which occurs d uring a similar time course as previously documented for tubular cell proli feration and especially tubular cell apoptosis in this model, may contribut e to injurious interactions of activated inflammatory cells with tubular ep ithelium. Copyright (C) 2000 S. Karger AG. Basel.