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  • Title: Both IgG- and C1q-receptors play a role in the enhanced binding of IgG complexes to human mesangial cells.
    Author: van den Dobbelsteen ME, van der Woude FJ, Schroeijers WE, Klar-Mohamad N, van Es LA, Daha MR.
    Journal: J Am Soc Nephrol; 1996 Apr; 7(4):573-81. PubMed ID: 8724891.
    Abstract:
    The presence of immunoglobulin G (IgG) in the mesangial area in kidneys of patients with different forms of glomerulonephritis suggests a role for IgG in the inflammatory process. This study investigates whether IgG is able to bind to cultured human mesangial cells (MC) in vitro. Incubation of MC with 125I-aggregated IgG(125I-AIgG), as a model for immune complexes (IC), at 4 degrees C resulted in a time- and dose-dependent binding of 125I-AIgG to MC. The binding of 125I-AIgG to MC was inhibited by excess AIgG or Fc-fragments and not by F(ab')2-fragments or human serum albumin (HSA). Scatchard analysis revealed the presence of 2.8.10(6) receptors/cell with an affinity of 9.7.10(7) M-1. Incubation of MC with 125I-C1q resulted in a time- and dose-dependent binding of 125I-C1q to MC. The binding of 125I-C1q was inhibited by excess C1q or C1q talls and not by HSA. Scatchard analysis revealed the presence of 3.2.10(7) binding sites/cell with an affinity of 1.4.10(7) M-1. Immunoprecipitation of 125I-labeled MC membrane proteins with C1q or monoclonal antibodies directed against human C1q-R revealed a single 66 to 68 kd band under reducing conditions. Fluorescence-activated cell-sorter analysis revealed an average of 60.1% +/- 5.4% of the cells positive with a mean channel of fluorescence of 592. A cooperative effect between C1q-R and Fc gamma-R in the binding of 125I-AIgG to MC, was assessed by incubation of 125I-AIgG in the presence of increasing concentrations of C1q, C1q talls, or delta C1q. Only intact C1q showed a 6- to 11-fold enhancement in binding of 125I-AIgG to MC. These studies demonstrate the occurrence of C1q-R and Fc gamma-R on MC and indicate that binding of IC is enhanced after interaction of IC with C1q.
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