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

Kidney Int. 2002 Aug;62(2):465-75. doi: 10.1046/j.1523-1755.2002.00477.x.


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 Fc(alpha)-R (CD89). Biochemical and molecular approaches were used to assess expression of CD89 and ASGP-R by MC.

Results: At 4 degrees 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 degrees 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibody Affinity
  • Antigen-Antibody Complex / immunology*
  • Antigen-Antibody Complex / metabolism
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Asialoglycoprotein Receptor / genetics
  • Asialoglycoprotein Receptor / metabolism
  • Asialoglycoproteins / metabolism
  • Carcinoma, Hepatocellular
  • Gene Expression / immunology
  • Glomerular Mesangium / cytology
  • Glomerular Mesangium / immunology*
  • Glomerular Mesangium / metabolism
  • Humans
  • Immunoglobulin A / immunology*
  • Immunoglobulin A / metabolism
  • Orosomucoid / analogs & derivatives*
  • Orosomucoid / metabolism
  • Protein Binding / immunology
  • RNA, Messenger / analysis
  • Receptors, Fc / genetics
  • Receptors, Fc / metabolism
  • Secretory Component / metabolism
  • U937 Cells


  • Antigen-Antibody Complex
  • Antigens, CD
  • Asialoglycoprotein Receptor
  • Asialoglycoproteins
  • Fc(alpha) receptor
  • Immunoglobulin A
  • Orosomucoid
  • RNA, Messenger
  • Receptors, Fc
  • Secretory Component
  • asialoorosomucoid