title: Fractalkine expression on human renal tubular epithelial cells: potential role in mononuclear cell adhesion.
abstract: Fractalkine (CX3CL1) is a transmembrane molecule with a CX3C chemokine domain attached to an extracellular mucin stalk which can induce both adhesion and migration of leucocytes. Mononuclear cell infiltration at renal tubular sites and associated tubular epithelial cell damage are key events during acute renal inflammation following renal allograft transplantation. Using northern and Western blot analysis, we have demonstrated the expression of fractalkine message and protein by renal tubular epithelial cells in vitro. The expression was up-regulated by TNF-alpha, a key proinflammatory cytokine in acute rejection. Investigation of surface expression of fractalkine on cultured proximal tubular epithelial cells revealed only a subpopulation of positively staining cells. Immunohistochemistry revealed that only a proportion of tubules in renal allograft biopsies showed induction of fractalkine expression. Studies using a static model of adhesion demonstrated CX3CR1/fractalkine interactions accounted for 26% of monocytic THP-1 cell and 17% of peripheral blood natural killer cell adhesion to tubular epithelial cells, suggesting that fractalkine may have a functional role in leucocyte adhesion and retention, at selected tubular sites in acute renal inflammation. Thus, fractalkine blockade strategies could reduce mononuclear cell mediated tubular damage and improve graft survival following kidney transplantation.
authors.affiliation: Renal Immunobiology, MRC Centre for Immune Regulation, The Medical School, University of Birmingham, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Chakravorty
authors.forename: P
authors.initials: P
authors.lastname: Cockwell
authors.forename: J
authors.initials: J
authors.lastname: Girdlestone
authors.forename: C J
authors.initials: CJ
authors.lastname: Brooks
authors.forename: C O S
authors.initials: CO
authors.lastname: Savage
mesh_terms: D000208:Acute Disease; D000073883:CX3C Chemokine Receptor 1; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006084:Graft Rejection / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007249:Inflammation; D016030:Kidney Transplantation; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D018121:Receptors, Cytokine / Q000502:physiology; D015728:Receptors, HIV / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; D015815:Cell Adhesion Molecules; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008565:Membrane Proteins; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha