BOTH IGG-RECEPTORS AND C1Q-RECEPTORS PLAY A ROLE IN THE ENHANCED BINDING OF IGG COMPLEXES TO HUMAN MESANGIAL CELLS

The presence of immunoglobulin G (IgG) in the mesangial area in kidney s of patients with different forms of glomerulonephritis suggests a ro le for IgG in the inflammatory process. This study investigates whethe r IgG is able to bind to cultured human mesangial cells (MC) in vitro. Incubation of MC with I-125-aggregated IgG (I-125-AlgG), as a model f or immune complexes (IC), at 4 degrees C resulted in a time- and dose- dependent binding of I-125-AlgG to MC, The binding of I-125-AlgG to MC was inhibited by excess AlgG or Fc-fragments and not by F(ab')(2)-fra gments or human serum albumin (HSA). Scatchard analysis revealed the p resence of 2.8 . 10(6) receptors/cell with an affinity of 9.7 . 10(7) M(-1). Incubation of MC with I-125-Clq resulted in a time- and dose-de pendent binding of I-125-Clq to MC. The binding of I-125-Clq was inhib ited by excess Clq or Clq tails and not by HSA. Scatchard analysis rev ealed the presence of 3.2 . 10(7) binding sites/cell with an affinity of 1.4 . 10(7) M(-1). Immunoprecipitation of I-125-labeled MC membrane proteins with Clq or monoclonal antibodies directed against human Clq -R revealed a single 66 to 68 kd band under reducing conditions. Fluor escence-activated cell-sorter analysis revealed an average of 60.1% +/ - 5.4% of the cells positive with a mean channel of fluorescence of 59 2. A cooperative effect between Clq-R and Fc gamma R in the binding of I-125-AlgG to MC, was assessed by incubation of I-125-AlgG in the pre sence of increasing concentrations of Clq, Clq tails, or delta Clq. On ly intact Clq showed a 6- to 11-fold enhancement in binding of I-125-A lgG to MC, These studies demonstrate the occurrence of Clq-R and Fc ga mma R on MC and indicate that binding of IC is enhanced after interact ion of IC with Clq.