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Expression of the chemokine receptor CCR1 in human renal allografts
Verena Mayer1, Kelly L Hudkins, Florian Heller
1Medizinische Poliklinik-Innenstadt, Pettenkoferstrasse 8a, 80336 Munich, Germany.
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.
Insights
Chemokine receptor CCR1 (CC chemokine receptor 1) is present on monocytes, B cells, and dendritic cells in human kidney allografts. Increased CCR1 mRNA in biopsies correlates with poorer renal function and allograft rejection.
Area of Science:
- Immunology
- Nephrology
- Transplantation
Background:
- Chemokines mediate leukocyte recruitment to allografts.
- CCR1 blockade reduces renal allograft injury in rabbits.
- Understanding CCR1-positive cells in human renal allografts is crucial.
Purpose of the Study:
- To characterize CCR1-positive cells in human renal allografts.
- To investigate the role of CCR1 in renal allograft injury.
Main Methods:
- Immunohistochemistry and double immunofluorescence on human renal allograft nephrectomies.
- Analysis of CCR1 mRNA and chemokine ligand expression (CCL3, CCL5) in renal allograft biopsies.
- Correlation with clinical parameters like serum creatinine.
Main Results:
- CCR1 protein expressed on circulating monocytes, CD20+ B cells, and DC-SIGN+ dendritic cells in allografts.
- CCR1 mRNA significantly increased in acute rejection and chronic allograft nephropathy.
- CCR1 mRNA levels correlated with chemokine ligands and serum creatinine.
Conclusions:
- CCR1 mRNA expression is linked to renal function in allografts.
- Interstitial macrophages are largely CCR1-negative, suggesting downregulation post-migration.
- CCR1-positive cells include monocytes, B cells, and dendritic cells in human renal allografts.
