Oxidative stress-mediated cardiac mast cell degranulation

Abstract

Pulmonary mast cell degranulation is a well-characterized response to diesel exhaust exposure. A primary constituent of fossil fuel combustion is sulfur dioxide (SO₂). SO₂ 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 SO₂-induced oxidative stress directly triggers the activation of cardiac mast cells. Accordingly, this study sought to determine whether Na₂SO₃ 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 Na₂SO₃ (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 Na₂SO₃ in order to determine their efficacy in preventing mast cell degranulation. Na₂SO₃ 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 SO₂ 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 SO₂-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.

Keywords:

• reactive oxygen species
• pollution
• oxidative stress
• mast cell
• cardiac remodeling

Acknowledgments

This study was supported in part by funding from the Environmental Protection Agency (EPA) RD831953 (GLB) and by Philip Morris USA Inc. and Philip Morris International and American Heart Association Postdoctoral Fellowship (0825510E) (SPL). Although the research described in the article has been funded in part by the US EPA's Science to Achieve Results (STAR) program through grant RD831953, it has not been subjected to any EPA review and therefore does not necessarily reflect the views of the agency, and no official endorsement should be inferred.