Interactions of human mesangial cells with IgA and IgA-containing immune complexes

Academic Article

Abstract

  • Background. IgA nephropathy (IgAN) is characterized by IgA1-containing immune complexes in mesangial deposits and in the circulation. The circulating immune complexes (CIC) are composed of galactose- (Gal) deficient IgA1 and IgG or IgA1 antibodies specific for the Gal-deficient IgA1; interactions of these CIC with mesangial cells (MC) were studied. Methods. Binding, internalization, and catabolic degradation of myeloma IgA1 protein as a standard control and the isolated CIC were studied using human MC, hepatoma cell line HepG2 expressing the asialoglycoprotein receptor (ASGP-R), and monocyte-like cell line U937 expressing the Fcα-R (CD89). Biochemical and molecular approaches were used to assess expression of CD89 and ASGP-R by MC. Results. At 4°C, radiolabeled IgA1 bound to MC and HepG2 cells in a dose-dependent and saturable manner. The binding was inhibited by IgA-containing CIC or excess IgA1 or its Fc fragment but not by the Fab fragment of IgA1. At 37°C, the cell-bound IgA1 was internalized and catabolized. In addition to IgA1, HepG2 cells also bound (in a Ca2+-dependent manner), internalized, and catabolized asialoorosomucoid (ASOR), other asialo-(AS)-glycoproteins, and secretory component (SC). The binding by MC appeared to be restricted to IgA1 or AS-IgA1 and was not Ca2+-dependent. Furthermore, MC and HepG2 cells internalized and catabolized IgA1-containing CIC. Using RT-PCR with ASGP-R- or CD89-specific primers, mRNAs of the two respective genes were not detected in MC. Conclusions. The data showed that the ability of MC to bind IgA1 and IgA1-containing CIC in vitro was mediated by an IgA receptor that was different from CD89 or ASGP-R and had a higher affinity for IgA-CIC than for uncomplexed IgA.
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    Author List

  • Novak J; Vu HL; Novak L; Julian BA; Mestecky J; Tomana M
  • Start Page

  • 465
  • End Page

  • 475
  • Volume

  • 62
  • Issue

  • 2