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 ext rahepatic tissues, but its expression in renal cells is not well estab lished. This study examines the presence of ASGP-R in cultured mesangi al cells (MC), key cells involved in the removal of macromolecules dep osited in the glomerulus. The binding of asialo-orosomucoid (ASOR) to rat MC was saturable and galactose-specific. In addition, MC internali zed and degraded ASOR in a Ca2+-dependent manner. Parallel studies wer e performed in a homologous system (human MG), obtaining similar bindi ng curve and competition with unlabeled ASOR and carbohydrates. The pu rified receptor from rat MC consisted of two proteins (41 and 55 kD) w ith 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 I gA1 with the mesangial ASGP-R was explored. As for the interaction wit h ASOR, catabolism of IgA 1 by rat and human MC was Ca2+-dependent and was reduced with galactose. In addition, the interaction of ASOR with rat MC was partially inhibited by incubation with IgA1 and its desial ylated form, but not by IgA2, as demonstrated in binding experiments a nd in receptor purification. It is concluded that MC possess ASGP-R sp ecific for galactose residues of several glycoproteins, including IgA1 . These data could be important for a better understanding of the path ogenesis of IgA nephropathy.