The Duffy antigen receptor for chemokines is up-regulated during acute renal transplant rejection and crescentic glomerulonephritis

Background Recruitment of leukocytes during immune responses requires the c oordinate expression of adhesion molecules in concert with chemokines and t heir receptors. The Duffy antigen receptor for chemokines (DARC) binds mult iple chemokines and is expressed on postcapillary venules in the normal kid ney. The chemokine receptor CCR5, which shares the ligand regulated upon ac tivation, normal T-cell expressed and secreted (RANTES) with DARC, is expre ssed by infiltrating T cells in the renal interstitium. As DARC might be in volved in the attraction of CCR5-positive cells, we studied the distributio n of DARC and CCR5 in two forms of cell-mediated renal injury: renal allogr aft rejection and crescentic glomerulonephritis (cGN). Methods. A total of 87 renal specimens. including 12 pre transplant biopsie s, 47 transplant biopsies (Banff 1, N = 10: Banff 2, N = 19; and various ot her lesions N = 18), and 28 biopsies from patients with cGN, was analyzed. Immunohistochemistry for CCR5 and DARC was performed on serial sections of formalin-fixed and paraffin-embedded tissue. Results. Compared with pretransplant biopsies, the mean number of DARC-posi tive interstitial venules was significantly increased during both transplan t rejection and cGN. This was accompanied by an infiltration of CCR5-positi ve leukocytes. During transplant rejection, the number and distribution of CCR5-positive cells correlated with DARC-positive venules. Infiltrating CCR 5-positive leukocytes were found mainly in the interstitium, often clusteri ng around Bowman's capsules in biopsies from cGN. The number of glomerular CCR5 positive cells is low, but they are common in a subset of crescents. Conclusions. We hypothesize that the increased number of DARC-positive venu les in areas of interstitial injury and the colocalization with CCR5-positi ve infiltrating leukocytes may indicate a role for endothelial DARC express ion during leukocyte adhesion and interstitial infiltration.