In vitro decrease of glomerular heparan sulfate by lymphocytes from idiopathic nephrotic syndrome patients.
BACKGROUND
Lymphocytes are involved in the physiopathologic mechanism of idiopathic nephrotic syndrome (INS). We have recently demonstrated that plasma 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 cells (PBMCs), PBL, and monocytes from patients and controls. The amounts of GAG and HS were assessed using a cationic membrane after metabolic labeling.


RESULTS
In coculture with GECs, mononuclear cells from controls decreased total epithelial cell GAG (-30% with PBMC, P < 0.05; -25% with PBL, P < 0.02; -19% with monocytes, P < 0.05). Particularly HSs were decreased (-36% with 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 in 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, supernatants of stimulated PBMCs from patients decreased also GAG and HS in comparison with controls (-13%, P < 0.02; -15%, P < 0.02, respectively, for GAG and HS).


CONCLUSIONS
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.
Department of Pediatrics, University Hospital of Geneva, Geneva, Switzerland.
B
B
Birmele
G
G
Thibault
H
H
Nivet
A
A
de Agostini
E P
EP
Girardin
D002478:Cells, Cultured; D002648:Child; D002809:Chondroitin Sulfates / Q000378:metabolism; D006025:Glycosaminoglycans / Q000737:chemistry / Q000378:metabolism; D006497:Heparan Sulfate / Q000037:antagonists & inhibitors*; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008214:Lymphocytes / Q000502:physiology*; D009000:Monocytes / Q000502:physiology; D009404:Nephrotic Syndrome / Q000378:metabolism* / Q000473:pathology; D011108:Polymers / Q000378:metabolism; D012016:Reference Values
D002809:Chondroitin Sulfates; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D011108:Polymers