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Glomerular endothelial injury associated with free radical production induced by a fungal cell wall component,
N Iwamoto1, T Yoshioka, K Nitta
1Department of Pediatric Nephrology, Tokyo Women's Medical College, Japan.
Abstract:
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.
Insights
Fungal (1-->3) beta-D glucan, a fungal cell wall component, triggers hydroxyl radical production and glomerular endothelial injury. This mechanism may explain microangiopathy in systemic fungal infections.
Area of Science:
- Nephrology
- Immunology
- Mycology
Background:
- Clinical evidence links fungal infections to microangiopathy.
- Fungal cell walls contain (1-->3) beta-D glucan, a potential mediator of cellular damage.
Purpose of the Study:
- To investigate the toxic effects of (1-->3) beta-D glucan on glomerular endothelial cells.
- To elucidate the role of free radical production in fungal-induced endothelial injury.
Main Methods:
- Cultured transformed glomerular endothelial cells (TF-GEN) were exposed to varying concentrations and durations of (1-->3) beta-D glucan.
- Hydroxyl radical production was measured using electron paramagnetic resonance spectrometry.
- Lactate dehydrogenase (LDH) release was assessed as a marker of cell injury.
- The effect of the antioxidant U78517F on radical production was evaluated.
Main Results:
- Exposure to (1-->3) beta-D glucan caused a concentration- and time-dependent increase in hydroxyl radical production.
- Radical production was comparable to that induced by E. coli lipopolysaccharide (LPS).
- Increased free radical production correlated with enhanced LDH release, indicating cell injury.
- Pretreatment with the antioxidant U78517F significantly reduced free radical production.
Conclusions:
- Fungal (1-->3) beta-D glucan induces glomerular endothelial injury via stimulation of cellular free radical production.
- This pathway is a potential mechanism underlying microangiopathy in systemic fungal infections.
- Antioxidant intervention may offer a therapeutic strategy against fungal-induced endothelial damage.