Mesangial cells possess an asialoglycoprotein receptor with affinity for human immunoglobulin A.
Asialoglycoprotein receptor (ASGP-R), a hepatic lectin involved in the clearance of galactose-terminal glycoproteins, is also present in extrahepatic tissues, but its expression in renal cells is not well established. This study examines the presence of ASGP-R in cultured mesangial cells (MC), key cells involved in the removal of macromolecules deposited in the glomerulus. The binding of asialo-orosomucoid (ASOR) to rat MC was saturable and galactose-specific. In addition, MC internalized and degraded ASOR in a Ca(2+)-dependent manner. Parallel studies were performed in a homologous system (human MC), obtaining similar binding curve and competition with unlabeled ASOR and carbohydrates. The purified receptor from rat MC consisted of two proteins (41 and 55 kD) with similar size to the hepatic receptor. Both subunits were detected by mRNA expression analysis (ratio 2:1). Because the hepatic receptor presents avidity for the carbohydrates of IgA1, a protein deposited in the glomerulus of patients with IgA nephropathy, the interaction of IgA1 with the mesangial ASGP-R was explored. As for the interaction with ASOR, catabolism of IgA1 by rat and human MC was Ca(2+)-dependent and was reduced with galactose. In addition, the interaction of ASOR with rat MC was partially inhibited by incubation with IgA1 and its desialylated form, but not by IgA2, as demonstrated in binding experiments and in receptor purification. It is concluded that MC possess ASGP-R specific for galactose residues of several glycoproteins, including IgA1. These data could be important for a better understanding of the pathogenesis of IgA nephropathy.
Gómez-Guerrero
C
C
Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.
Duque
N
N
Egido
J
J
D000818:Animals; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D008969:Molecular Sequence Data; D009961:Orosomucoid / Q000031:analogs & derivatives / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*
D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D007070:Immunoglobulin A; D009961:Orosomucoid; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C017030:asialoorosomucoid