EXPERIMENTAL STUDIES ON THE ROLE OF INTERCELLULAR-ADHESION MOLECULE-1AND LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1 IN HYPERTENSIVE NEPHROSCLEROSIS

T helper cells and macrophages infiltrate into the renal cortical inte rstitium during the course of hypertensive nephrosclerosis. To investi gate the mechanisms of mononuclear cell infiltration, we examined the expression of the intercellular adhesion molecule-1 (ICAM-1) and its c ounterpart lymphocyte function-associated antigen-1 (LFA-I) in the pro gression of hypertensive renal injury. We studied nonclipped kidneys o f two-kidney, one clip renovascular hypertensive and sham-operated con trol rats immunohistochemically at 4, 7, 14, and 28 days after clippin g (n = 5 per group and time point). Systolic pressure was significantl y elevated by day 7 (154 +/- 4 versus 117 +/- 6 mm Hg in sham, P < .05 ). The development of hypertension resulted in a progressive increase of ICAM-1 expression in the perivascular and interstitial areas of the renal cortex and on proximal tubular brush borders. Only a few glomer uli showed augmented ICAM-1 staining. Increased ICAM-1 was associated with an accumulation of LFA-1-positive mononuclear cells in the periva scular region (day 14: 15 +/- 4 versus 2 +/- 0.2 cells/mm(2) in sham, P < .005) and intertubular region (127 +/- 11 versus 32 +/- 3 cells pe r millimeter squared in sham, P < .005). The maximum was obtained at d ay 14 and remained elevated until day 28. In addition, the number of i nterstitial LFA-1-positive infiltrating cells was related to the degre e of interstitial and tubular ICAM-1 expression and correlated with bl ood pressure (r = .75, P < .001, n = 18). Our data suggest that ICAM-1 is involved in the recruitment of macrophages/lymphocytes via specifi c interaction of ICAM-1 and LFA-1 in this model of hypertensive target -organ damage.