Sd. Ricardo et al., EXPRESSION OF ADHESION MOLECULES IN RAT RENAL-CORTEX DURING EXPERIMENTAL HYDRONEPHROSIS, Kidney international, 50(6), 1996, pp. 2002-2010
Unilateral ureteral obstruction (UUO) is associated with an early and
steadily increasing infiltration of macrophages into the renal cortica
l interstitium. As adhesion molecules may play an important role in ma
crophage recruitment following the mechanical disturbance after UUO, w
e delineated the tilne course of inlercellular adhesion molecule (ICAM
)-1 and vascular adhesion molecule (VCAM)-1 mRNA and protein expressio
n. 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 a
t 12, 24, 48, and 96 hours after obstruction. respectively, in compari
son to the contralateral unobstructed kidney (CUK). Despite an apparen
t relief of obstruction, four weeks followin_g reversal of obstruction
mRNA levels of ICAM-1 remained equivalent to the 96-hour obstructed k
idney group. No significant difference in ICAM-1 mRNA expression was o
bserved between the obstructed kidneys and CUK specimens. Immunohistoc
hemistry revealed focal labeling of ICAM-1 on the apical and basolater
al surface of the rrnal tubules, peritubuiar interstitium, and vessels
of the renal cortex by 12 hours after UUO. In contrast, only faint st
aining for ICAM-1 protein was observed in the cortex from CUK specimen
s. The obstructed and CUK specimens exhibited diffuse immunolocalizati
on of VCAM-1 in the cortical tubules and Bowmans capsular epithelium.
In situ hybridization showed mRNA transcription for ICAM-1 localized i
n the peritubular interstitium and cortical tubules from obstructed ki
dneys. To lend mechanistic insight into the response of ICAM-1 to the
mechanical disturbance after UUO, the expression of ICAM-1 mRNA was ex
amined when freshly isolated proximal tubules were exposed to angioten
sin II (1 to 1000 mu M) immediately after preparation. Levels of ICAM-
1 mRNA were elevated 1.4-, 7.1-, and 3.7-fold when exposed to 10 mu M
100 mu M and 1000 mu M of angiotensin II for one hour. respectively, w
hen compared to control cultures. The addition of losartan to proximal
tubules for one hour prior to angiotensin II stimulation decreased IC
AM-1 levels to control values. In summary, this investigation demonstr
ates that ICAM-1 is important in the: initiation of macrophage recruit
ment into the renal cortex of the obstructed kidney. These findings pr
ovide evidence that angiotensin II, produced after ureteral ligation a
s a result of tubular injury and dysfunction, may play a central role
in the release of ICAM-1 from the proximal tubule epithelial cells.