IngentaConnect Fractalkine expression on human renal tubular epithelial cells: p...

Authors: CHAKRAVORTY, S. J.¹; COCKWELL, P.¹; GIRDLESTONE, J.²; BROOKS, C. J.¹; SAVAGE, C. O. S.¹

Source: Clinical & Experimental Immunology, Volume 129, Number 1, July 2002 , pp. 150-159(10)

Abstract:

SUMMARY

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-α, 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.

Keywords: Fractalkine TNF-α renal epithelial cell adhesion

Document Type: Research article

DOI: 10.1046/j.1365-2249.2002.01906.x

Affiliations: 1: Renal Immunobiology, MRC Centre for Immune Regulation, 2: Department of Anatomy, MRC Centre for Immune Regulation, The Medical School, University of Birmingham, B15 2TT, UK.

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Fractalkine expression on human renal tubular epithelial cells: potential role in mononuclear cell adhesion