In vitro decrease of glomerular heparan sulfate by lymphocytes from idiopathic nephrotic syndrome patients

Background. Lymphocytes are involved in the physiopathologic mechanism of i diopathic nephrotic syndrome (INS). We have recently demonstrated that plas ma from patients with INS decreases human glomerular epithelial cell (GEC) glycosaminoglycans (GAGs), particularly heparan sulfates (HS) in vitro. In this study we investigate the effect of peripheral blood lymphocytes (PBL) from INS patients on glomerular cell GAG and HS. Methods. Human GECs were cultured with total peripheral blood mononuclear c ells (PBMCs), PBL, and monocytes from patients and controls. The amounts of GAG and HS were assessed using a cationic membrane after metabolic labelin g. Results. In coculture with GECs, mononuclear cells from controls decreased total epithelial cell GAG (-30% with PBMC, P < 0.05; -25% with PBL, P < 0.0 2; -19% with monocytes, P < 0.05). Particularly HSs were decreased (-36% wi th PBMC, P < 0.05; -27% with PBL, P < 0.02; and -19% with monocytes, P < 0. 05). When GECs were in coculture with PBL from INS patients, the decrease i n GAG and HS was significantly greater in comparison to control PBL (-10%, P < 0.02; -10%, P < 0.02, respectively, for GAG and HS). Moreover, supernat ants of stimulated PBMCs from patients decreased also GAG and HS in compari son with controls (-13%, P < 0.02; -15%, P < 0.02, respectively, for GAG an d HS). Conclusion. These data provide direct evidence that PBLs from INS patients are able to decrease GEC HS as previously shown with plasma from patients. This might be instrumental in the onset of albuminuria.