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Alterations in intracellular reactive oxygen species generation and redox potential modulate mast cell function
1Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, GB.
European Journal of Immunology
|January 1, 1997
Summary
Certain chemicals trigger autoimmune responses by increasing reactive oxygen species (ROS) in mast cells, impacting their function and mediator release. Modulating ROS production influences these chemically induced autoimmune effects.
Area of Science:
- Immunology
- Toxicology
- Cell Biology
Background:
- Mercuric chloride, gold compounds, and D-penicillamine induce a T helper (Th)2 cell-associated autoimmune syndrome in Brown Norway rats.
- These agents sensitize rat peritoneal mast cells for IgE-triggered mediator release and interleukin-4 mRNA production in vitro.
- The hypothesis posits that these agents affect mast cell function through intracellular reactive oxygen species (ROS) production and redox balance.
Purpose of the Study:
- To investigate the role of intracellular ROS production and redox balance in chemically induced mast cell activation.
- To determine if mercuric chloride, gold compounds, and D-penicillamine influence mast cell function via ROS generation.
Main Methods:
- Mast cells were isolated from Brown Norway rats via peritoneal washout.
- Cells were incubated with mercuric chloride, gold compounds, or D-penicillamine (with copper ions) to assess ROS production using 2',7'-dichlorofluorescein.
- The effect of direct oxidative stress (H2O2) and modulation of ROS (desferrioxamine, catalase, glutathione, 2-mercaptoethanol) on mast cell mediator release was evaluated.
Main Results:
- Incubation with the tested compounds induced intracellular ROS production in mast cells, with mast cells being more sensitive than splenocytes.
- Direct oxidative stress sensitized mast cells for mediator release, similar to mercuric chloride.
- Inhibition of ROS formation or replenishment of glutathione reduced HgCl2-enhanced IgE-mediated serotonin release.
- Modulation of ROS production/redox balance affected the compounds' impact on mast cell function.
Conclusions:
- The tested compounds induce ROS generation within mast cells, supporting their role in mast cell sensitization.
- Direct oxidative stress sensitizes mast cells for mediator release.
- Modulation of ROS production and redox balance influences the effects of these compounds on mast cell function, highlighting the importance of oxidative/antioxidative balance in chemically induced autoimmunity.