Expression of the chemokine receptor CCR1 in human renal allografts.
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.
Mayer
Verena
V
Medizinische Poliklinik-Innenstadt, Pettenkoferstrasse 8a, 80336 Munich, Germany.
Hudkins
Kelly L
KL
Heller
Florian
F
Schmid
Holger
H
Kretzler
Matthias
M
Brandt
Ulrike
U
Anders
Hans-Joachim
HJ
Regele
Heinz
H
Nelson
Peter J
PJ
Alpers
Charles E
CE
Schlöndorff
Detlef
D
Segerer
Stephan
S
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D018951:Antigens, CD20 / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050476:Bowman Capsule / Q000276:immunology / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D007684:Kidney Tubules / Q000276:immunology / Q000473:pathology; D037181:Lectins, C-Type / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D054389:Receptors, CCR1; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D014184:Transplantation, Homologous / Q000276:immunology; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; D000097382:CD68 Molecule
D015703:Antigens, CD; D018951:Antigens, CD20; D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D054389:Receptors, CCR1; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C515300:CCR1 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule