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

Clin Exp Immunol. 2002 Jul;129(1):150-9. doi: 10.1046/j.1365-2249.2002.01906.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • CX3C Chemokine Receptor 1
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology
  • Cell Adhesion Molecules / biosynthesis
  • Cell Adhesion Molecules / genetics
  • Cells, Cultured / drug effects
  • Cells, Cultured / metabolism
  • Chemokine CX3CL1
  • Chemokines, CX3C / biosynthesis
  • Chemokines, CX3C / genetics
  • Chemokines, CX3C / pharmacology
  • Chemokines, CX3C / physiology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Gene Expression Regulation / drug effects
  • Graft Rejection / metabolism
  • Graft Rejection / pathology*
  • Humans
  • Inflammation
  • Kidney Transplantation*
  • Kidney Tubules, Proximal / metabolism*
  • Kidney Tubules, Proximal / pathology
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / metabolism
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics
  • Membrane Proteins / pharmacology
  • Membrane Proteins / physiology*
  • Monocytes / cytology
  • Monocytes / metabolism
  • Receptors, Cytokine / physiology
  • Receptors, HIV / physiology
  • Recombinant Proteins / pharmacology
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology


  • CX3C Chemokine Receptor 1
  • CX3CL1 protein, human
  • Cell Adhesion Molecules
  • Chemokine CX3CL1
  • Chemokines, CX3C
  • Membrane Proteins
  • Receptors, Cytokine
  • Receptors, HIV
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha