title: Characterization of CXCL16 and ADAM10 in the normal and transplanted kidney.
abstract: The chemokine CXCL16 plays an important role in the recruitment of leukocytes to sites of inflammation influencing the course of experimental glomerulonephritis. Here we show that human kidneys highly express CXCL16 in the distal tubule, connecting tubule and principal cells of the collecting duct with weak expression in the thick ascending limb of Henle. Beside the membrane localization, a soluble form of CXCL16 can be proteolytically released which acts as a chemotactic factor. In human renal tissue the expression pattern of the disintegrin-like metalloproteinase ADAM10 is similar to that of CXCL16, suggesting ADAM10 can potentially cleave CXCL16 in vivo. When we tested this in primary tubular cells we found that blockade of ADAM10 activity inhibited the IFN-gamma induced release of soluble CXCL16. Acute tubular damage in renal allografts was associated with elevated urinary CXCL16 and this correlated with focally increased apical CXCL16 expression in the distal tubules and collecting ducts. Renal allograft biopsies, with a histopathological diagnosis of acute interstitial rejection, showed increased basolateral ADAM10 expression together with high numbers of infiltrating T cells. Our results suggest that CXCL16 and ADAM10 are involved in the recruitment of T cells to the kidney and play an important role in inflammatory kidney diseases.
authors.affiliation: 1pharmazentrum frankfurt/ZAFES, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schramme
authors.forename: Mohamed Sadek
authors.initials: MS
authors.lastname: Abdel-Bakky
authors.forename: Paul
authors.initials: P
authors.lastname: Gutwein
authors.forename: Nicholas
authors.initials: N
authors.lastname: Obermüller
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Baer
authors.forename: Ingeborg A
authors.initials: IA
authors.lastname: Hauser
authors.forename: Andreas
authors.initials: A
authors.lastname: Ludwig
authors.forename: Stefan
authors.initials: S
authors.lastname: Gauer
authors.forename: Liliana
authors.initials: L
authors.lastname: Schäfer
authors.forename: Ewelina
authors.initials: E
authors.lastname: Sobkowiak
authors.forename: Peter
authors.initials: P
authors.lastname: Altevogt
authors.forename: Michael
authors.initials: M
authors.lastname: Koziolek
authors.forename: Eva
authors.initials: E
authors.lastname: Kiss
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gröne
authors.forename: Ritva
authors.initials: R
authors.lastname: Tikkanen
authors.forename: Itamar
authors.initials: I
authors.lastname: Goren
authors.forename: Heinfried
authors.initials: H
authors.lastname: Radeke
authors.forename: Josef
authors.initials: J
authors.lastname: Pfeilschifter
mesh_terms: D051722:ADAM Proteins / Q000276:immunology / Q000378:metabolism*; D000072197:ADAM10 Protein; D000328:Adult; D000368:Aged; D053829:Amyloid Precursor Protein Secretases / Q000276:immunology / Q000378:metabolism*; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000276:immunology / Q000378:metabolism* / Q000652:urine; D002634:Chemotaxis, Leukocyte; D005260:Female; D015870:Gene Expression; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D016030:Kidney Transplantation / Q000276:immunology*; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D051116:Receptors, Scavenger / Q000276:immunology / Q000378:metabolism*; D012995:Solubility; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D008565:Membrane Proteins; D051116:Receptors, Scavenger; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human