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  • Title: Immune complex activation of rat glomerular mesangial cells: dependence on the Fc region of antibody.
    Author: Knauss TC, Mené P, Ricanati SA, Kester M, Dubyak GR, Emancipator SN, Sedor JR.
    Journal: Am J Physiol; 1989 Sep; 257(3 Pt 2):F478-85. PubMed ID: 2506766.
    Abstract:
    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 region of immunoglobulin G (IgG). We now studied the effects of soluble IC on mesangial cell cytosolic free calcium ([Ca2+]i) and phosphatidylinositol turnover as putative mechanisms of transmembrane signaling as well as prostaglandin biosynthesis and contraction. IC (500 micrograms 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 micrograms 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.(ABSTRACT TRUNCATED AT 250 WORDS)
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