Expression of the chemokine receptor CCR1 in human renal allografts

Nephrol Dial Transplant. 2007 Jun;22(6):1720-9. doi: 10.1093/ndt/gfm007. Epub 2007 Feb 13.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics
  • Antigens, CD20 / biosynthesis
  • Antigens, Differentiation, Myelomonocytic / biosynthesis
  • Antigens, Differentiation, Myelomonocytic / genetics
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / metabolism
  • Bowman Capsule / immunology
  • Bowman Capsule / pathology
  • Cell Adhesion Molecules / biosynthesis
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology
  • Female
  • Humans
  • Kidney Function Tests
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / pathology
  • Kidney Tubules / immunology
  • Kidney Tubules / pathology
  • Lectins, C-Type / biosynthesis
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Monocytes / metabolism
  • Monocytes / pathology
  • Receptors, CCR1
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Chemokine / biosynthesis*
  • Receptors, Chemokine / chemistry
  • Receptors, Chemokine / genetics
  • Transplantation, Homologous / immunology

Substances

  • Antigens, CD
  • Antigens, CD20
  • Antigens, Differentiation, Myelomonocytic
  • CCR1 protein, human
  • CD68 antigen, human
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Receptors, CCR1
  • Receptors, Cell Surface
  • Receptors, Chemokine