Macrophages, monocyte chemoattractant peptide-1, and TGF-beta 1 in experimental hydronephrosis

Abstract

Early cellular and molecular derangements have been evaluated as potential pivotal factors for the late development of interstitial fibrosis after experimental hydronephrosis. In this study, we delineated the kinetics of renal cortical macrophage infiltration as well as the cortical expression of transforming growth factor-beta 1 (TGF-beta 1) and monocyte chemoattractant peptide-1 (MCP-1) at 12, 48, and 96 h after unilateral ureteral obstruction (UUO). Interstitial macrophage number in the obstructed kidney versus the contralateral unobstructed kidney (CUK) significantly increased by 12 (11.1 +/- 0.9 vs. 4.5 +/- 0.6), 48 (27.5 +/- 0.9 vs. 4.0 +/- 0.8), and 96 h (71.4 +/- 4.6 vs. 3.2 +/- 0.4) after UUO. MCP-1 mRNA was detected from 12 to 96 h in the obstructed kidney but was absent in the CUK specimens at all time points. Apical tubular MCP-1 expression, on immunolabeling, was present from 12 through 96 h after UUO in the obstructed kidney but not the CUK specimen. On Northern analysis, there were highly significant 2.6-, 5.8-, and 7.0-fold increments in renal cortical TGF-beta 1 mRNA levels at 12, 48, and 96 h, respectively, in the obstructed kidney versus the CUK specimen. Intracellular TGF-beta 1, on immunolabeling, was detected only in the obstructed kidneys of UUO rats at all three time points and was confined to peritubular cells of the renal interstitium. A significant (P < 0.005) correlation (r = 0.95) between interstitial macrophage number and cortical TGF-beta 1 mRNA levels was noted.(ABSTRACT TRUNCATED AT 250 WORDS)