EVIDENCE FOR A LIGAND-RECEPTOR SYSTEM MEDIATING THE BIOLOGIC EFFECTS OF GLYCATED ALBUMIN IN GLOMERULAR MESANGIAL CELLS

Mesangial cells cultured with albumin modified by Amadori glucose addu cts exhibit decreased proliferation in association with increased elab oration of Type TV collagen. To test the hypothesis that this modulati on of mesangial cell biology is linked to ligand binding, we examined renal glomerular mesangial cells for the expression of receptors that interact with Amadori-modified albumin. Murine mesangial cells bound g lycated albumin in a dose-dependent and saturable manner, displaying h igh and low affinity binding sites. Binding of glycated but not nongly cated albumin was inhibited by monoclonal antibodies that specifically react with albumin containing fructosyllysine groups. LDL containing Amadori glucose adducts did not compete with glycated albumin for bind ing. These results are consistent with ligand selectivity of the bindi ng sites for an Amadori-modified sequence within an albumin domain and suggest that a ligand receptor system mediates the effects of glycate d albumin on mesangial cell proliferation and matrix production. (C) 1 995 Academic Press, Inc.