NDT Advance Access originally published online on February 13, 2007
Nephrology Dialysis Transplantation 2007 22(6):1720-1729; doi:10.1093/ndt/gfm007
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Expression of the chemokine receptor CCR1 in human renal allografts
1Medizinische Poliklinik-Innenstadt, University of Munich, Germany, 2Department of Pathology, University of Washington, Seattle, WA, USA and 3Clinical Institute of Pathology, University of Vienna, Vienna, Austria
Correspondence and offprint requests to: Stephan Segerer, Medizinische Poliklinik-Innenstadt, Pettenkoferstrasse 8a, 80336 Munich, Germany. Email: stephan.segerer{at}lrz.uni-muenchen.de
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Abstract |
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Background. Chemokines are involved in the recruitment of leukocytes to vascularized allografts. CCR1 is a receptor for various proinflammatory chemokines and CCR1 blockade reduces renal allograft injury in rabbits. The purpose of the study was to characterize CCR1-positive cells in human renal allografts.
Methods. Formalin-fixed, paraffin-embedded allograft nephrectomies (n = 9) and non-involved parts of tumour nephrectomies (n = 10) were studied. Immunohistochemistry for CCR1, CD3 and CD68 was performed on consecutive sections. Double immunofluorescence for CCR1 and CD3, CD20, CD68, DC-SIGN and S100 was used on selected cases. Expression of CCR1 mRNA and the ligands CCL3 and CCL5 was studied in renal allograft biopsies with acute rejection (n = 10), with chronic allograft nephropathy (n = 8) and controls (n = 8).
Results. CCR1 protein was expressed by circulating cells in glomerular and peritubular capillaries, colocalizing with CD68. In renal allografts CCR1-positive cells were present within glomerular tufts, but only scattered CCR1-positive cells were found in tubulointerstitial infiltrates. CCR1 did not colocalize with the majority of CD68-positive cells in the interstitium. The small number of CCR1-positive interstitial cells were identified as CD20- or DC-SIGN-positive by double immunofluorescence. CCR1 mRNA was significantly increased in renal biopsies with acute allograft rejection (P < 0.001), and with chronic allograft nephropathy (P < 0.05), it correlated with the expression of CCL3 and CCL5, and with serum-creatinine.
Conclusions. CCR1 mRNA expression was associated with renal function in allografts. CCR1 protein expression was restricted to monocytes, CD20-positive B cells and DC-SIGN-positive dendritic cells. Thus most interstitial macrophages were CCR1 negative, which may relate to down-regulation after migration into the interstitium in human renal allografts.
Keywords: allograft rejection; CCL5; CCR1; CD20; chemokines; DC-SIGN
Received for publication: 10. 9.06
Accepted in revised form: 4. 1.07