Expression of the C-C chemokine receptor 5 in human kidney diseases1

Segerer, Stephan; Mack, Matthias; Regele, Heinz; Kerjaschki, Dontscho; Schlöndorff, Detlef
July 1999
Kidney International;Jul1999, Vol. 56 Issue 1, p52
Academic Journal
Expression of the C-C chemokine receptor 5 in human kidney diseases. Background.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. Methods.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. Results.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....


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