Glomerular endothelial injury associated with free radical production induced by a fungal cell wall component, (1-->3) beta-D glucan.
Clinical evidence suggests that microangiopathy may be induced by fungal infection. The present study evaluated the toxic effect of (1-->3) beta-D glucan, a major component of fungal cell wall, on cultured transformed glomerular endothelial cells (TF-GEN). When TF-GEN were exposed to increasing concentrations of (1-->3) beta-D glucan (beta-DG; 115 to 430 pg/ml) for 1 to 3 hours, concentration- and time-dependent increases in hydroxyl radical production were demonstrated by electron paramagnetic resonance spectrometry using 5, 5-dimethyl-1-pyrrolyne-N-oxide as a spin trap agent. The amount of radicals induced by 230 or 430 pg/ml beta-DG was comparable to that induced by E. coli LPS (1 or 10 microg/ml). The beta-DG-induced free radical production was associated with a subsequent increase in LDH release from TF-GEN. When TF-GEN pretreated with U78517F (0.1 or 1.0 microM), a lipophilic antioxidant, were stimulated with LPS (1 or 10 microg/ml) or beta-DG (230 pg/ml) for 3 hours, free radical production by TF-GEN was significantly reduced in cells pretreated with the higher concentration of U78517F. Thus, fungal (1-->3) beta-D glucan induces glomerular endothelial injury by stimulating cellular free radical production. Such a mechanism may underlie microangiopathy in systemic fungal infections.
Iwamoto
N
N
Department of Pediatric Nephrology, Tokyo Women's Medical College, Japan.
Yoshioka
T
T
Nitta
K
K
Ito
K
K
D000818:Animals; D002176:Candida albicans / Q000378:metabolism*; D002177:Candidiasis / Q000150:complications; D002417:Cattle; D002473:Cell Wall / Q000378:metabolism*; D002839:Chromans / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D005936:Glucans / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D014652:Vascular Diseases / Q000209:etiology / Q000378:metabolism; D047071:beta-Glucans
D002839:Chromans; D016166:Free Radical Scavengers; D005609:Free Radicals; D005936:Glucans; D010879:Piperazines; D047071:beta-Glucans; C066382:U 78517F; C033363:beta-1,3-glucan