RAT MESANGIAL CELLS EXPRESS MACROPHAGE-MIGRATION INHIBITORY FACTOR IN-VITRO AND IN-VIVO

Mesangial cells are thought to promote glomerular macrophage accumulat ion in glomerulonephritis. This may occur through the production of ma crophage migration inhibitory factor (MIF), a molecule known to regula te macrophage accumulation at sites of inflammation. To study this, gl omerular MIF expression and macrophage accumulation were examined in r at anti-Thy-1 disease, a model of mesangioproliferative nephritis. In situ hybridization and immunohistochemistry showed that MIF is express ed by some podocytes in normal rat glomeruli. De novo MIF expression b y glomerular endothelium was seen on day 1 of anti-Thy-1 disease. On d ay 6, glomerular MIF mRNA and protein expression were prominent in seg mental proliferative lesions, which was also the location of most infi ltrating macrophages. Double-staining identified de nova MIF mRNA and protein expression by proliferating mesangial cells within these lesio ns. Cytokine regulation of mesangial cell MIF expression was examined in vitro. Northern blotting showed that cultured rat mesangial cells e xpress a single 0.6-kb species of MIF mRNA, and Western blotting detec ted a single protein band of 12.5 kD. Six-hour stimulation of mesangia l cells with interferon-gamma or platelet-derived growth factor signif icantly increased MIF mRNA levels. However, the addition of recombinan t MIF to mesangial cells did not affect mesangial cell proliferation o r constitutive transforming growth factor-beta mRNA expression, nor di d MIF induce monocyte chemoattractant protein-1 mRNA expression. In co nclusion, this is the first study to demonstrate that mesangial cells can produce MIF in vivo and in vitro. It is postulated that mesangial cell MIF production in response to injury acts to promote macrophage a ccumulation within segmental proliferative lesions in rat anti-Thy-1 n ephritis.