Role of Oxidants in Mast Cell Activation

Abstract

Reactive oxygen species (ROS), such as superoxide, hydrogen peroxide (H2O2), and hydroxyl radical, have for a long time been considered as accidental by-products of respiratory energy production in mitochondria and as being useless and rather deleterious to biological systems. Contrary to such a classical view, accumulating evidence indicates that upon stimulation of divergent receptor systems, ROS are intentionally produced and even required for appropriate signal transduction and biological responses. Work by our group and that of others have shown that stimulation of mast cells through the high-affinity IgE receptor (FcepsilonRI) induces the production of ROS such as superoxide and H2O2 possibly by the phagocyte NADPH oxidase homologue and that these endogenously produced oxidants have important functions in regulation of various mast cell responses, including degranulation, leukotriene secretion, and cytokine production. Subsequent studies have defined particular biochemical pathways that can be targeted by ROS and/or cellular redox balance. More recent research reveals that ROS may also play an important role in mast cell activation by divergent allergy-relevant environmental substances, for instance heavy metals and polycyclic aromatic hydrocarbons. This review summarizes current knowledge on the role of endogenous oxidants in mast cell activation.

ETAselective receptor antagonism prevents ventricular remodeling in volume-overloaded rats

“…A possible mechanism by which ET-1 receptor antagonism could mediate effects over cardiac mast cell density or activation is through the reduction of myocardial oxidative stress. In vitro studies have identified reactive oxygen species as an initiator of mast cell cytokine expression and histamine release (50,52). Recent work by Gilles et al (24) demonstrated a role for oxidative stress in mast cell activation in vivo following ischemia and reperfusion.…”

Effects of nonselective endothelin-1 receptor antagonism on cardiac mast cell-mediated ventricular remodeling in rats

“…The findings from that study showed corresponding increases in mast cell secretory products (i.e., histamine or TNF-␣) and elevated myocardial oxidants. Furthermore, in vitro studies have identified intracellular reactive oxygen species as the initiator of mast cell cytokine expression and histamine release (2,40,44). Recent reports have demonstrated that treatment of ischemic myocardium with either selective (ET A , BQ-123) or nonselective (ET A /ET B , bosentan) receptor antagonism significantly reduced catalase and superoxide dismutase activity as well as glutathione content (21,36).…”

Smoking, Metalloproteinases, and Vascular Disease

“…75 Mast cells are activated by oxidized LDL 76 and reactive oxygen species. 77 T lymphocytes in atherosclerotic plaques also express matrix metalloproteinases. 50 T lymphocytes are activated by oxidized LDL, 78 inflammatory cytokines, 79 and interaction with adhesion molecules.…”