Expression of adhesion molecules in rat renal cortex during experimental hydronephrosis

Abstract

Unilateral ureteral obstruction (UUO) is associated with an early and steadily increasing infiltration of macrophages into the renal cortical interstitium. As adhesion molecules may play an important role in macrophage recruitment following the mechanical disturbance after UUO, we delineated the time course of intercellular adhesion molecule (ICAM)-1 and vascular adhesion molecule (VCAM)-1 mRNA and protein expression. A significant 6.6- (P < 0.001), 2.6- (P < 0.025), 2.6- (P < 0.01), and 2.0-fold (P < 0.005) increase in ICAM-1 mRNA expression was observed at 12, 24, 48, and 96 hours after obstruction, respectively, in comparison to the contralateral unobstructed kidney (CUK). Despite an apparent relief of obstruction, four weeks following reversal of obstruction mRNA levels of ICAM-1 remained equivalent to the 96-hour obstructed kidney group. No significant difference in VCAM-1 mRNA expression was observed between the obstructed kidneys and CUK specimens. Immunohistochemistry revealed focal labeling of ICAM-1 on the apical and basolateral surface of the renal tubules, peritubular interstitium, and vessels of the renal cortex by 12 hours after UUO. In contrast, only faint staining for ICAM-1 protein was observed in the cortex from CUK specimens. The obstructed and CUK specimens exhibited diffuse immunolocalization of VCAM-1 in the cortical tubules and Bowman's capsular epithelium. In situ hybridization showed mRNA transcription for ICAM-1 localized in the peritubular interstitium and cortical tubules from obstructed kidneys. To lend mechanistic insight into the response of ICAM-1 to the mechanical disturbance after UUO, the expression of ICAM-1 mRNA was examined when freshly isolated proximal tubules were exposed to angiotensin II (1 to 100 microM) immediately after preparation. Levels of ICAM-1 mRNA were elevated 1.4-, 7.1-, and 3.7-fold when exposed to 10 microM, 100 microM, and 1000 microM of angiotensin II for one hour, respectively, when compared to control cultures. The addition of losartan to proximal tubules for one hour prior to angiotensin II stimulation decreased ICAM-1 levels to control values. In summary, this investigation demonstrates that ICAM-1 is important in the initiation of macrophage recruitment into the renal cortex of the obstructed kidney. These findings provide evidence that angiotensin II, produced after ureteral ligation as a result of tubular injury and dysfunction, may play a central role in the release of ICAM-1 from the proximal tubule epithelial cells.