Intrarenal infusion of supernatant from cytokine-activated human mesangial cells may cause glomerular damage.
BACKGROUND
The pathogenesis of glomerular damage in glomerulonephritis (GN) is not fully understood. Several studies have suggested that reactive oxygen molecules play a role in renal disease. It is known that, during GN, mesangial cells are activated. In a previous study, we demonstrated that in vitro interleukin (IL)-1 plus IL-6 stimulated cultured human mesangial cell (HMC) activation to release free oxygen radicals.


METHODS
In this study, we measured hydrogen peroxide (H2O2) and superoxide anion (O2-) levels after stimulation by IL-1 plus IL-6 in cultured HMCs. We then infused H2O2 directly into the left renal arteries of Sprague-Dawley rats. We also infused the culture supernatants of HMCs after stimulation by IL-1 plus IL-6 into the left renal arteries of rats. Two hours after stopping the infusion, the kidneys were removed and fixed using Carson's modified Millonig's buffer for electron microscopy.


RESULTS
Both 100 microM H2O2 and supernatants of HMCs stimulated by IL-1 10 U/ml plus IL-6 1,000 U/ml caused similar glomerular damage, including blebbing and sloughing of endothelial cells, and denuded basement membrane in glomeruli. When 100 microM H2O2 or supernatants of cytokine-activated HMCs were infused into renal arteries, they caused hematuria and proteinuria.


CONCLUSIONS
These results suggest that activated HMCs may secrete free radicals and cause glomerular damage.
Chen
W P
WP
Department of Pediatrics, Taipei Veterans General Hospital, Taiwan, ROC.
Tan
S K
SK
Chen
A
A
Lin
C Y
CY
D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D016207:Cytokines / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000378:metabolism; D005921:Glomerulonephritis / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D013481:Superoxides / Q000378:metabolism
D016207:Cytokines; D017382:Reactive Oxygen Species; D013481:Superoxides; D006861:Hydrogen Peroxide