title: The chemokine receptor CXCR7 is expressed on lymphatic endothelial cells during renal allograft rejection.
abstract: CXCR7 is an atypical receptor for the chemokines CXCL11 and CXCL12, which were found to be involved in animal models of allograft injury. We studied the expression of CXCR7 and its ligands in human kidneys by first quantifying the mRNA in 53 renal allograft biopsies. Receptor and ligand mRNAs were expressed in renal allografts, with a significant induction of CXCL11 and CXCL12 in biopsies showing borderline lesions and acute rejection. Immunohistochemical analysis for CXCR7 was performed in a series of 64 indication and 24 protocol biopsies. The indication biopsies included 46 acute rejections, 6 with interstitial fibrosis and tubular atrophy, and 12 pretransplant biopsies as controls. In control biopsies, CXCR7 protein was found on smooth muscle and on endothelial cells of a small number of peritubular vessels. The number of CXCR7-positive vessels was increased in acute rejection and, using double immunofluorescence labeling, a subset of these CXCR7-positive endothelial cells were identified as lymphatic vessels. Both CXCR7-positive blood and lymphatic vessels increased during allograft rejection. We found that CXCR7 is present in both blood and lymphatic endothelial cells in human renal allografts. Whether its presence modulates the formation of chemokine gradients and the recruitment of inflammatory cells will require further experimental studies.
authors.affiliation: Division of Nephrology, University Hospital, Zurich 8091, Switzerland.
authors.forename: Matthias A
authors.initials: MA
authors.lastname: Neusser
authors.forename: Anna K
authors.initials: AK
authors.lastname: Kraus
authors.forename: Heinz
authors.initials: H
authors.lastname: Regele
authors.forename: Clemens D
authors.initials: CD
authors.lastname: Cohen
authors.forename: Thomas
authors.initials: T
authors.lastname: Fehr
authors.forename: Dontscho
authors.initials: D
authors.lastname: Kerjaschki
authors.forename: Rudolf P
authors.initials: RP
authors.lastname: Wüthrich
authors.forename: Mark E T
authors.initials: ME
authors.lastname: Penfold
authors.forename: Thomas
authors.initials: T
authors.lastname: Schall
authors.forename: Stephan
authors.initials: S
authors.lastname: Segerer
mesh_terms: D001706:Biopsy; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054371:Chemokine CXCL11 / Q000235:genetics / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008024:Ligands; D009392:Nephrectomy; D012333:RNA, Messenger / Q000276:immunology / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D054371:Chemokine CXCL11; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; D008024:Ligands; D012333:RNA, Messenger; D019707:Receptors, Chemokine