Immune complex activation of rat glomerular mesangial cells: dependence on the Fc region of antibody
Knauss, T.C.; Mené, P.; Ricanati, S.A.; Kester, M.; Dubyak, G.R.; Emancipator, S.N.; Sedor, J.R.
American Journal of Physiology 257(3 Pt 2): F478-F485
1989
ISSN/ISBN: 0002-9513 PMID: 2506766 Document Number: 336441
Glomerulonephritis is frequently associated with immunoglobulin deposition in the mesangium. We had previously shown that contractile, rat mesangial cells in culture synthesize superoxide anion after binding immune complexes (IC) in a manner dependent on the Fc regoin of immunoglobulin G (IgG). We now studied the effects of soluble IC on mesangial cell cystolic free calcium ([Ca2+]i) and phosphatidylinositol turnover as putative mechanisms of transmembrane signaling as well as prostaglandin biosynthesis and contraction. IC (500 .mu.g specific antibody) raised [Ca2+]i in mesangial cells loaded with fura-2 from resting levels of 100.4 .+-. 8.0 to a peak of 282.3 .+-. 31.5 nM in a dose-dependent manner. Removal of extracellular Ca2+ by ethylene glycol-bis(.beta.-aminoethyl ether)-N,N,N',N'-tetraacetic acid only slightly reduced peak, IC-stimulated [Ca2+]i to 236 .+-. 18 nM but prevented the sustained phase of the response, indicating that IC both mobilized Ca2+ from intracellular stores and increased the influx of Ca2+ across the plasma membrane. IC did not increase water-soluble inositol phosphates, measured by anion-exchange chromatography of trichloroacetic acid-extracted cells but markedly stimulated PGE2 and thromboxane B2 synthesis in a dose- and time-dependent manner. Finally, IC (250 .mu.g specific antibody) induced 45.8 .+-. 10.1% of the cells to contract with an average decrease in cross-sectional surface area of 20.0 .+-. 1.8% of basal as assessed by image-analysis microscopy. IC formed with F(ab')2 fragments of antibody and antigen or mixtures of antigen and nonimmune whole molecule antibody did not alter [Ca2+]i, induce prostaglandin synthesis, or stimulate mesangial cell contraction. These experiments provide further evidence that cultured mesangial cells express Fc receptors for IgG (Fc.gamma.R). We propose that Fc.gamma.R-mediated activation of mesangial cells contributes to the structural, biochemical, and functional changes characteristic of IC glomerular injury.