Expression of the C-C chemokine receptor 5 in human kidney diseases

Background. Chemokines are proteins that contribute to the migration of leu kocytes to sites of tissue injury. CCR5 is a receptor for the C-C chemokine RANTES, which is expressed in inflammatory kidney diseases and transplant rejection. Methods. In order to study the distribution of CCR5, we developed a series of monoclonal antibodies against human CCR5. These antibodies were then eva luated by flow cytometry, Western blot, and immunohistochemistry on formali n-fixed, paraffin-embedded tonsils. Eighty biopsies from patients with memb ranous glomerulonephritis (N = 9), ISA nephropathy (N = 10), lupus nephriti s (N = 10), membranoproliferative glomerulonephritis (N = 10), acute inters titial nephritis (N = 13, chronic interstitial nephritis (N = 10), acute tr ansplant rejection (N = 9), and chronic transplant rejection (N = 9) were s tained for CCR5 and CD3 expression in parallel sections. Results. One monoclonal antibody (MC-5) showed a single protein band of app roximately 38 kD corresponding to CCR5 in Western blot, By indirect immunoh istochemistry, a cell membrane signal was detected exclusively on mononucle ar inflammatory cells. All control stainings with an isotype-matched mouse IgG2a were negative. CCR5-positive cells were identified in areas of inters titial infiltration in biopsies of chronic glomerulonephritis, interstitial nephritis, and transplant rejection. The staining of CCR5 showed the same distribution as CD3-positive T cells. In patients with impaired renal funct ion, a significantly higher number of CCR5-positive cells were found as com pared with patients with normal renal function. In contrast to the prominen ce of CCR5-positive cells in the interstitial infiltrate, the number of CCR 5-positive cells within the glomeruli was low, even in cases with prolifera tive glomerulonephritis. No CCR5 expression could be detected on intrinsic cells of glomerular, tubular, or vascular structures. Conclusions. The pattern of CCR5 and CD3 cell infiltration suggests that CC R5-positive T cells may play a role in interstitial processes leading to fi brosis, Further studies are required to define the pathophysiological relev ance of these cells in progressive renal diseases.