Experimental studies on the role of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 in hypertensive nephrosclerosis.
T helper cells and macrophages infiltrate into the renal cortical interstitium during the course of hypertensive nephrosclerosis. To investigate the mechanisms of mononuclear cell infiltration, we examined the expression of the intercellular adhesion molecule-1 (ICAM-1) and its counterpart lymphocyte function-associated antigen-1 (LFA-1) in the progression of hypertensive renal injury. We studied nonclipped kidneys of two-kidney, one clip renovascular hypertensive and sham-operated control rats immunohistochemically at 4, 7, 14, and 28 days after clipping (n = 5 per group and time point). Systolic pressure was significantly 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 glomeruli showed augmented ICAM-1 staining. Increased ICAM-1 was associated with an accumulation of LFA-1-positive mononuclear cells in the perivascular region (day 14: 15 +/- 4 versus 2 +/- 0.2 cells/mm2 in sham, P < .005) and intertubular region (127 +/- 11 versus 32 +/- 3 cells per millimeter squared in sham, P < .005). The maximum was obtained at day 14 and remained elevated until day 28. In addition, the number of interstitial LFA-1-positive infiltrating cells was related to the degree of interstitial and tubular ICAM-1 expression and correlated with blood pressure (r = .75, P < .001, n = 18). Our data suggest that ICAM-1 is involved in the recruitment of macrophages/lymphocytes via specific interaction of ICAM-1 and LFA-1 in this model of hypertensive target-organ damage.
Mai
M
M
Department of Internal Medicine-Nephrology, University of Erlangen-Nürnberg, Germany.
Hilgers
K F
KF
Geiger
H
H
D000818:Animals; D001835:Body Weight; D006977:Hypertension, Renal / Q000209:etiology / Q000503:physiopathology*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D007668:Kidney / Q000473:pathology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D008297:Male; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1