title: Fractalkine expression in human renal inflammation.
abstract: Immune and inflammatory human renal disease is associated with heavy mononuclear cell infiltration. The trafficking of these cells to extravascular sites is directed by local production of chemokines. Fractalkine is the first described cell-surface anchored chemokine and has potent mononuclear cell-directed adhesion and chemotactic properties. The purpose of this study was to analyse the expression and distribution of fractalkine in human renal inflammation. In situ hybridization and immunohistochemistry were used to study renal biopsies from 15 patients with predominant glomerular inflammation (vasculitic glomerulonephritis) and 15 with predominant tubular and interstitial inflammation (acute renal allograft rejection). Controls comprised non-inflammatory glomerulonephritis and normal tissue. Fractalkine mRNA was predominantly expressed in the major compartment, glomerular or tubulointerstitial, affected by disease and with the strongest expression localized to vascular sites local to inflammation. In acute renal allograft rejection, there was increased expression of fractalkine mRNA by tubular epithelial cells. There was no expression of fractalkine by infiltrating leukocytes and there was only sparse expression in control tissue. Fractalkine mRNA expression correlated with infiltrating leukocyte subsets. Immunohistochemistry confirmed this pattern of expression, with serial section co-localization showing fractalkine expression in areas with macrophage (CD68+) and T cell (CD3+) infiltrates. These expression patterns show that fractalkine is a strong candidate for directing mononuclear cell infiltration in human renal inflammation.
authors.affiliation: Department of Renal Immunobiology, Division of Medical Sciences, Medical School, University of Birmingham, Birmingham, UK. paul.cockwell@university-bim.wmids.nhs.uk
authors.forename: Paul
authors.initials: P
authors.lastname: Cockwell
authors.forename: Srabasti J
authors.initials: SJ
authors.lastname: Chakravorty
authors.forename: John
authors.initials: J
authors.lastname: Girdlestone
authors.forename: Caroline O S
authors.initials: CO
authors.lastname: Savage
mesh_terms: D000208:Acute Disease; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis; D001327:Autoimmune Diseases / Q000378:metabolism; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005921:Glomerulonephritis / Q000378:metabolism*; D006084:Graft Rejection / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D016030:Kidney Transplantation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D014657:Vasculitis / Q000378:metabolism*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008565:Membrane Proteins; D012333:RNA, Messenger