Oxidative stress-mediated cardiac mast cell degranulation
Oxidative stress-mediated cardiac mast cell degranulation
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DOI：
10.1080/02772240903306409
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发表时间：
2010-01-01
影响因子：
1.8
通讯作者：
Brower, Gregory L.
中科院分区：
文献类型：
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作者：
Melendez, Giselle C.;Voloshenyuk, Tetyana G.;Brower, Gregory L.
肺肥大细胞脱颗粒是柴油机废气暴露的典型反应。化石燃料燃烧的主要成分是二氧化硫（SO2）。SO2在继发于细胞内氧化应激的永生化细胞系中诱导肥大细胞脱颗粒；然而，二氧化硫诱导的氧化应激是否直接触发心肌肥大细胞的激活尚不清楚。因此，本研究试图确定Na2SO3是否诱导心肌肥大细胞脱颗粒，以及是否可以通过抑制氧化应激来阻止心肌肥大细胞的活化。为此，从心外膜表面分离出心肌肥大细胞，用浓度增加的Na2SO3（0、0.5或5 mM）孵育。针对不同自由基生成机制的抗氧化剂化合物，包括艾布selen、二苯二酮（DPI）或-生育酚，在5 mM的Na2SO3中孵育，以确定它们对阻止肥大细胞脱颗粒的功效。Na2SO3诱导心肌肥大细胞的组胺释放呈浓度依赖性，范围为8.87% ~ 18.86%，ebselen可阻止这一作用。在这些条件下，DPI和-生育酚没有影响。综上所述，这些结果表明SO2能够在体外产生心肌肥大细胞脱颗粒；然而，评估的三种抗氧化剂的不同有效性表明了介导二氧化硫诱导的心脏肥大细胞脱颗粒的多因素机制。埃布selen在预防肥大细胞脱颗粒方面的特殊效果可能与其预防氧化应激的多种机制有关。
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 -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 -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.