title: Immune complex activation of rat glomerular mesangial cells: dependence on the Fc region of antibody.
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)
authors.affiliation: Cleveland Veterans Administration Medical Center, Ohio.
authors.forename: T C
authors.initials: TC
authors.lastname: Knauss
authors.forename: P
authors.initials: P
authors.lastname: Mené
authors.forename: S A
authors.initials: SA
authors.lastname: Ricanati
authors.forename: M
authors.initials: M
authors.lastname: Kester
authors.forename: G R
authors.initials: GR
authors.lastname: Dubyak
authors.forename: S N
authors.initials: SN
authors.lastname: Emancipator
authors.forename: J R
authors.initials: JR
authors.lastname: Sedor
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000502:physiology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D007074:Immunoglobulin G; D007295:Inositol Phosphates / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats
chemical_list: D000936:Antigen-Antibody Complex; D001095:Arachidonic Acids; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007295:Inositol Phosphates; D011453:Prostaglandins; D016718:Arachidonic Acid; D002118:Calcium