Interactions of human mesangial cells with IgA and IgA-containing 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(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.
Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294,USA. Jan_Novak@microbio.uab.edu
Jan
J
Novak
Huong L
HL
Vu
Lea
L
Novak
Bruce A
BA
Julian
Jiri
J
Mestecky
Milan
M
Tomana
D000915:Antibody Affinity; D000936:Antigen-Antibody Complex / Q000276:immunology* / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D037263:Asialoglycoprotein Receptor / Q000235:genetics / Q000378:metabolism; D001212:Asialoglycoproteins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular; D015870:Gene Expression / Q000276:immunology; D005920:Glomerular Mesangium / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology* / Q000378:metabolism; D009961:Orosomucoid / Q000031:analogs & derivatives* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism; D012635:Secretory Component / Q000378:metabolism; D020298:U937 Cells
D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D009961:Orosomucoid; D012333:RNA, Messenger; D011961:Receptors, Fc; D012635:Secretory Component; C017030:asialoorosomucoid