Cell Biology – Immunology – Pathology
Kidney International (2002) 62, 465–475; doi:10.1046/j.1523-1755.2002.00477.x
Interactions of human mesangial cells with IgA and IgA-containing immune complexes1
Jan Novak, Huong L Vu, Lea Novak, Bruce A Julian, Jiri Mestecky and Milan Tomana
Departments of Microbiology, Pathology, and Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
Correspondence: Dr Jan Novak, Department of Microbiology, University of Alabama at Birmingham, 845 19th Street S, BBRB 734, Birmingham, Alabama 35294, USA. E-mail: Jan_Novak@microbio.uab.edu
1See Editorial by Gómez-Guerrero, Suzuki, and Egido, p. 715.
Received 26 March 2001; Revised 7 March 2002; Accepted 22 March 2002.
Abstract
Interactions of human mesangial cells with IgA and IgA-containing circulating immune complexes.
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
-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.
Keywords:
renal mesangial cells, circulating immune complexes, IgA nephropathy, glomerulonephritis
