Contributions of mesangial cells to glomerular immune functions

Abstract

Mesangial cells play an important role in the maintenance of the structure and function of the glomerulus. In addition mesangial cells are capable of macromolecular uptake, and generation of autocoids and cytokines. Our studies have explored the mechanism of IgG uptake by cultured rat mesangial cells. Mesangial cells were found to express Fc receptors for IgG as demonstrated by specific binding studies, indirect immunofluorescence microscopy, immunoblotting and Northern blot analysis. The number of Fc receptors for IgG on mesangial cells was upregulated by interferon gamma, cyclic AMP and monocyte-macrophage specific colony stimulating factor--CSF-1. In addition uptake of IgG complexes was acutely increased by angiotensin II and inhibited by cAMP. These latter effects are independent of receptor number, but are mediated by changes in the cytoskeleton. These observations may be of significance for hemodynamically independent effects of vasoactive agents on mesangial function. Finally we examined the potential of mesangial cells for generation of CSF-1. Cultured mesangial cells produced radioimmunoassayable CSF-1 and expressed mRNA for CSF-1. Interferon gamma stimulated, whereas cAMP and agents increasing cAMP, such as forskolin and PGE2, inhibited CSF-1 production. This was due to decreased transcription resulting in lower levels of mRNA for CSF-1. The interactions of CSF-1, other cytokines, prostaglandins and cAMP may be important in regulating immune-like functions of mesangial cells, and especially their response to immunecomplexes.