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

Chemokines are proteins that contribute to the migration of leukocytes 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.

In order to study the distribution of CCR5, we developed a series of monoclonal antibodies against human CCR5. These antibodies were then evaluated by flow cytometry, Western blot, and immunohistochemistry on formalin-fixed, paraffin-embedded tonsils. Eighty biopsies from patients with membranous glomerulonephritis (N = 9), IgA nephropathy (N = 10), lupus nephritis (N = 10), membranoproliferative glomerulonephritis (N = 10), acute interstitial nephritis (N = 13), chronic interstitial nephritis (N = 10), acute transplant rejection (N = 9), and chronic transplant rejection (N = 9) were stained for CCR5 and CD3 expression in parallel sections.

One monoclonal antibody (MC-5) showed a single protein band of approximately 38 kD corresponding to CCR5 in Western blot. By indirect immunohistochemistry, a cell membrane signal was detected exclusively on mononuclear inflammatory cells. All control stainings with an isotype-matched mouse IgG2a were negative. CCR5-positive cells were identified in areas of interstitial 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 function, a significantly higher number of CCR5-positive cells were found as compared with patients with normal renal function. In contrast to the prominence of CCR5-positive cells in the interstitial infiltrate, the number of CCR5-positive cells within the glomeruli was low, even in cases with proliferative glomerulonephritis. No CCR5 expression could be detected on intrinsic cells of glomerular, tubular, or vascular structures.

The pattern of CCR5 and CD3 cell infiltration suggests that CCR5-positive T cells may play a role in interstitial processes leading to fibrosis. Further studies are required to define the pathophysiological relevance of these cells in progressive renal diseases.