concanavalin-a and Albuminuria

Diabetic mellitus is attended by the development of endothelial dysfunction which is suggested to be accompanied with a chronic low-degree of inflammation. During a chronic hepatic inflammatory response, specific changes in glycosylation of the acute phase protein alpha1-acid glycoprotein (AGP) can be detected. In this report we studied the changes in glycosylation of AGP in more detail and evaluated the relation between a change in glycosylation of AGP and urinary albumin secretion in Type I diabetic patients. The glycosylation of AGP, studied by crossed affinity immunoelectrophoresis (CAIE) and high pH anion exchange chromatography with pulse amperometric detection (HPAEC-PAD), showed an increase in alpha3-fucosylation. Staining with an antibody against sialyl Lewis(x) (sLe(x)) implied that part of the alpha3-fucosylation was present in a sLe(x)-conformation. In the group of Type I diabetic patients with increased urinary albumin excretion, a significant increase in alpha3-fucosylation of AGP (p<0.0005) could be detected. Therefore, the increased alpha3-fucosylation of AGP can be used as an additional marker for the development of vascular complications in Type I diabetic patients.

Topics: Adolescent; Adult; Aged; Albuminuria; Carbohydrate Conformation; Chromatography, Ion Exchange; Concanavalin A; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Female; Fucose; Fucosyltransferases; Glycosylation; Humans; Inflammation; Lectins; Male; Middle Aged; Oligosaccharides; Orosomucoid; Sialyl Lewis X Antigen; Statistics as Topic

Supernatants of peripheral blood mononuclear cell culture from children with minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) were tested for their ability to increase glomerular basement membrane (GBM) permeability and for effects on anionic sites in the GBM. Supernatants from cultures of concanavalin A-stimulated peripheral blood mononuclear cells from patients with MCNS, those with FSGS and normal controls were infused into the renal arteries of normal rats. Infusion of the supernatants from patients with MCNS and FSGS caused a significant reduction of anionic sites in the GBM (p less than 0.001) and a significant increase in urinary albumin excretion (p less than 0.05), whereas infusion of supernatants in control cases did not reduce anionic sites nor increase urinary albumin excretion. These findings show that stimulation of peripheral blood mononuclear cells from MCNS and FSGS with concanavalin A results in liberation of soluble substances which reduce polyanions in the GBM and increases GBM permeability.

Topics: Albuminuria; Animals; Cell Membrane; Cell Membrane Permeability; Cells, Cultured; Child; Concanavalin A; Culture Media; Glomerulosclerosis, Focal Segmental; Humans; Kidney Glomerulus; Male; Monocytes; Nephrosis, Lipoid; Rats; Rats, Inbred Strains; Reproducibility of Results