Oxidative stress-mediated cardiac mast cell degranulation

• Published in: Toxicological and environmental chemistry 2010-08, Vol.92 (7), p.1293-1301
• Main Authors: Meléndez, Giselle C., Voloshenyuk, Tetyana G., McLarty, Jennifer L., Levick, Scott P., Brower, Gregory L.
• Format: Article
• Language: English
• Subjects: Antioxidants; cardiac remodeling; Cellular biology; Heart; Histamine; mast cell; Oxidative stress; Physiology; pollution; reactive oxygen species; Sulfur
• ISSN: 0277-2248; 1029-0486
• DOI: 10.1080/02772240903306409

Pulmonary mast cell degranulation is a well-characterized response to diesel exhaust exposure. A primary constituent of fossil fuel combustion is sulfur dioxide (SO 2 ). SO 2 was shown to induce mast cell degranulation in an immortalized cell line secondary to induction of intracellular oxidative stress; however, it is not known whether SO 2 -induced oxidative stress directly triggers the activation of cardiac mast cells. Accordingly, this study sought to determine whether Na 2 SO 3 induces degranulation of cardiac mast cells, and furthermore whether cardiac mast cell activation may be prevented by inhibition of oxidative stress. To this end, cardiac mast cells were isolated from epicardial surface of the heart and incubated with increasing concentrations of Na 2 SO 3 (0, 0.5, or 5 mM). Antioxidant compounds targeting different mechanisms of free radical generation, including ebselen, diphenyleneiodonium (DPI), or α-tocopherol, were incubated with 5 mM of Na 2 SO 3 in order to determine their efficacy in preventing mast cell degranulation. Na 2 SO 3 induced a significant concentration-dependent histamine release from cardiac mast cells ranging from 8.87% to 18.86%, which was prevented by ebselen. No effect was observed with DPI and α-tocopherol under these conditions. In conclusion, these findings indicate that SO 2 is capable of producing cardiac mast cell degranulation in vitro; however, the variable effectiveness of the three antioxidants evaluated is indicative of a multifactorial mechanism mediating SO 2 -induced cardiac mast cell degranulation. The particular effectiveness of ebselen in preventing mast cell degranulation may be related to its multiple mechanisms of preventing oxidative stress.