Up-regulation of Duffy antigen receptor expression in children with renal disease

Background. The Duffy antigen chemokine receptor (DARC) is a promiscuous ch emokine receptor that binds chemokines from the C-X-C and C-C families. DAR C was initially described on red blood cells, but subsequent studies have d emonstrated DARC protein expression on renal endothelial and epithelial cel ls, even in Duffy-negative individuals whose red cells lack DARC. Because a pproximately 68% of African Americans lack the Duffy/DARC on their red cell s, we carried out experiments to identify the specific renal cells expressi ng DARC protein and mRNA in African American children and to define whether DARC expression was altered in renal inflammatory processes. Methods. Immunohistochemistry and in situ hybridization studies were done i n 28 renal sections from children with each of the following diagnoses: HIV nephropathy (HIVAN), HIV-associated hemolytic uremic syndrome (HIV-HUS), H IV infection without renal disease, HIV-negative children without renal dis ease, and Argentinean children with classic HUS. Results. The predominant localization of DARC mRNA and protein was found in endothelial cells underlying postcapillary renal venules in all patients s tudied. However, DARC mRNA and protein were significantly up-regulated in p eritubular and glomerular capillaries, collecting duct epithelial cells, an d interstitial inflammatory cells in children with HIVAN, HIV-HUS, and clas sic HUS. Conclusion. These findings support the notion that the renal DARC is linked to the inflammatory cascade and that African American children may be at r isk of accumulating chemokines in renal tissues.