Role for interactions between IP-10/Mig and CXCR3 in proliferative glomerulonephritis

The mechanisms responsible for mesangial cell proliferation in proliferativ e glomerulonephritis are only partially understood. This article reports th e results of an immunohistochemical study showing high expression of the ch emokine receptor CXCR3 by mesangial cells of patients with IgA nephropathy, membranoproliferative glomerulonephritis, or rapidly progressive glomerulo nephritis. CXCR3 was also detectable by flow cytometry in cultured human me sangial cells, in which it appeared to be functionally active, as determine d by the ability of its ligand, the (interferon-gamma)-inducible protein of 10 kD (IP-10) to induce intracellular Ca2+ influx. Both IP-10 and the mono kine induced by interferon-gamma (Mig) were also effective in inducing prol iferation of human mesangial cells. These data suggest that in patients wit h proliferative glomerulonephritis, the chemokines IP-10 and/or Mig not onl y may act as chemoattractants for infiltrating mononuclear cells in the inf lamed tissue, but also may directly induce the proliferation of mesangial c ells.