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首页> 外文学位 >Paradoxical effects of gallium arsenide on cathepsin L expression by antigen-presenting cells.
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Paradoxical effects of gallium arsenide on cathepsin L expression by antigen-presenting cells.

机译：砷化镓对抗原呈递细胞对组织蛋白酶L表达的反常效应。

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Gallium arsenide (GaAs) is an intermetallic semiconductor used in the electronics industry. Although industrial workers risk chemical exposure during the manufacture of GaAs, the human health effects are unknown. However, animal studies have determined that the chemical is a carcinogen and an immunotoxicant. Interestingly, GaAs produces paradoxical immunological effects in vivo depending on anatomical location. Aqueous soluble dissociation products of GaAs exposure cause systemic immunosuppression and impaired antigen processing. Antigen processing is the mechanism by which antigen-presenting cells (APC) degrade antigen and present it to helper T cells in the context of major histocompatibility complex molecules in order to elicit an immune response. Conversely, direct exposure to GaAs particles enhances antigen processing by APC at the site of exposure. Parallel to effects on antigen processing, GaAs also induces paradoxical effects on activity of the lysosomal protease cathepsin L (CathL), which plays an important role in antigen processing. Chemical exposure suppresses CathL activity in splenic APC but augments proteolytic activity at the site of chemical exposure. This study examined the mechanisms by which GaAs modulates CathL activity. Suppressed proteolytic activity was not caused by direct enzymatic inhibition or cellular toxicity. However, exposure to soluble GaAs components suppressed CathL, mRNA expression. In contrast, exposure to particulate GaAs augmented CathL mRNA and protein expression. Therefore, different forms of the chemical produce opposite effects on CathL expression. This is the first study to show that GaAs exposure can modulate gene expression, which may be an important mechanism by which the chemical may adversely affect human health.
机译：砷化镓（GaAs）是电子行业中使用的金属间半导体。尽管工业工人在制造砷化镓期间冒着化学物质接触的危险，但对人类健康的影响尚不清楚。但是，动物研究确定该化学物质是致癌物和免疫毒性物质。有趣的是，砷化镓在体内根据解剖学位置产生矛盾的免疫学作用。 GaAs暴露的水溶性离解产物会导致全身性免疫抑制和抗原加工受损。抗原加工是抗原呈递细胞（APC）降解抗原并在主要组织相容性复合物分子的背景下将其呈递给辅助T细胞以引发免疫反应的机制。相反，直接暴露于GaAs颗粒会增强APC在暴露部位的抗原加工能力。与对抗原加工的影响平行，GaAs还对溶酶体蛋白酶组织蛋白酶L（CathL）的活性产生反常效应，后者在抗原加工中起重要作用。化学暴露会抑制脾APC中的CathL活性，但会增加化学暴露部位的蛋白水解活性。这项研究检查了GaAs调节CathL活性的机制。抑制的蛋白水解活性不是由直接的酶抑制作用或细胞毒性引起的。但是，暴露于可溶性GaAs成分会抑制CathL，mRNA表达。相反，暴露于颗粒GaAs会增加CathL mRNA和蛋白质表达。因此，不同形式的化学物质对CathL表达产生相反的影响。这是第一项显示GaAs暴露可以调节基因表达的研究，这可能是该化学物质可能对人体健康产生不利影响的重要机制。

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