Distinct expression of CCR1 and CCR5 in glomerular and interstitial lesions of human glomerular diseases

We investigated the presence of CCR1- and CCR5-positive cells immunohistochemically in the kidneys of 38 patients with several renal diseases, including 13 crescentic glomerulonephritis patients. In addition, we determined cell phenotypes of CCR1- and CCR5-positive cells using a dual immunostaining technique. Urinary levels of their ligands, for CCR1 and CCR5; macrophage inflammaton/protein (MIP)-1 alpha, MIP-1 beta and regulated upon activation in normal T cells expressed and secreted (RANTES) were evaluated by enzyme-linked immunosorbent assay. CCR1- and CCR5-positive cells were detected in both glomeruli and interstitium of the diseased kidneys. Using a dual immunostaining technique, these positive cells were CD68-positive macrophages (M Phi) and CDS-positive T cells. The number of CCR1-positive cells in glomeruli was correlated with urinary levels of MIP-1 alpha. The number of CCR1-positive cells in the interstitium was correlated with both urinary MIP-1 alpha and RANTES levels. CCR1-positive cells in the interstitium remained after glucocorticoid therapy, most of which were M Phi, and were correlated with the intensity of interstitial fibrosis and tubular atrophy. Glomerular CCR5-positive cells were well correlated with extracapillary lesions and urinary MIP-1 alpha levels, while interstitial CCR5-positive cells, mainly CD3-positive T cells, were correlated with interstitial lesions and urinary RANTES levels. Renal CCR5-positive cells were dramatically decreased during convalescence induced by glucocorticoids. These results suggest that chemokine receptor signaling may be pivotal for human renal diseases through the recruitment and activation of M Phi and T cells; CCR5-positive cells may participate in glomerular lesions including extracapillary lesions via MIP-1 alpha and in interstitial lesions via RANTES. CCR1 may be involved in interstitial lesions in resolving phase after glucocorticoid therapy. Copyright (C) 2000 S. Karser AG, Basel.