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

Abstract

The Duffy antigen receptor for chemokines is up-regulated during acute renal transplant rejection and crescentic glomerulonephritis.BackgroundRecruitment of leukocytes during immune responses requires the coordinate expression of adhesion molecules in concert with chemokines and their receptors. The Duffy antigen receptor for chemokines (DARC) binds multiple chemokines and is expressed on postcapillary venules in the normal kidney. The chemokine receptor CCR5, which shares the ligand regulated upon activation, normal T-cell expressed and secreted (RANTES) with DARC, is expressed by infiltrating T cells in the renal interstitium. As DARC might be involved in the attraction of CCR5-positive cells, we studied the distribution of DARC and CCR5 in two forms of cell-mediated renal injury: renal allograft rejection and crescentic glomerulonephritis (cGN).MethodsA total of 87 renal specimens, including 12 pretransplant biopsies, 47 transplant biopsies (Banff 1, N = 10; Banff 2, N = 19; and various other 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.ResultsCompared with pretransplant biopsies, the mean number of DARC-positive interstitial venules was significantly increased during both transplant rejection and cGN. This was accompanied by an infiltration of CCR5-positive leukocytes. During transplant rejection, the number and distribution of CCR5-positive cells correlated with DARC-positive venules. Infiltrating CCR5-positive leukocytes were found mainly in the interstitium, often clustering 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.ConclusionsWe hypothesize that the increased number of DARC-positive venules in areas of interstitial injury and the colocalization with CCR5-positive infiltrating leukocytes may indicate a role for endothelial DARC expression during leukocyte adhesion and interstitial infiltration