Effect of arsenic exposure on alveolar macrophage function. II. Effect of slightly soluble forms of As(III) and As(V).
Effect of arsenic exposure on alveolar macrophage function. II. Effect of slightly soluble forms of As(III) and As(V).
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砷暴露对肺泡巨噬细胞功能的影响。
DOI：
10.1006/enrs.1995.1008
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发表时间：
1995
影响因子：
8.3
通讯作者：
Carter,DE
中科院分区：
文献类型：
--
作者：
Lantz,RC;Parliman,G;Chen,GJ;Barber,D;Winski,S;Carter,DE
物质的肺毒性取决于许多化学和物理特性，包括化合物的溶解度。在肺中，不溶性金属可能比可溶性金属更具致瘤性，尽管这种效应尚未定量且作用机制尚未阐明。通过确定体内和体外暴露后肺泡巨噬细胞 (PAM) 功能的变化来评估微溶形式的 As(III) 和 As(V) 的毒性作用。全程使用雄性斯普拉格-道利大鼠。气管内滴注 1 mg/kg（以砷计）三硫化二砷 (As(III)) 或砷酸钙 (As(V)) 24 小时后，对 PAM 进行灌洗并分析超氧化物 (O-2(-)) 和肿瘤坏死因子 (TNF-α) 产生的变化。支气管肺泡灌洗液中 TNF-α 没有差异。帕姆。从暴露于 As(V) 的动物身上进行灌洗后，O-2(-) 的产生和 TNF-α 的基础释放显着增加。从接受 As(III) 的动物身上灌洗的 PAM 没有显示出显着的变化。为了测试砷的直接影响，从对照动物身上灌洗PAM，并在体外暴露于浓度为0.1至300μg/ml的砷长达24小时。所使用的剂量对 PAM 没有细胞毒性，因为 LDH 释放没有显着增加。仅在接触砷 24 小时后，O-2(-) 产生的显着剂量依赖性抑制才明显。 As(III) 和 As(V) 在 10 μg/ml 浓度下均产生抑制作用。两种砷的浓度相似（4-5μg/ml）时，LPS诱导的TNF-α释放也受到抑制。砷都不会抑制前列腺素 E(2) 的产生。可溶性砷浓度的测量表明化合物的溶解不能解释所见的所有影响。砷引起的 PAM 功能改变可能会损害宿主防御。
The pulmonary toxicity of a substance depends on a number of chemical and physical characteristics, including the solubility of the compounds. In the lung, insoluble forms of metals may be more tumorigenic than soluble forms despite the fact that this effect has not been quantitated and the mechanism of action has not been elucidated. The toxic effects of slightly soluble forms of As(III) and As(V) were evaluated by determining alteration in function of pulmonary alveolar macrophages (PAM) following in vivo and in vitro exposure. Male Sprague-Dawley rats were used throughout. Twenty-four hours following intratracheal instillation of 1 mg/kg (as arsenic) of either arsenic trisulfide (As(III)) or calcium arsenate (As(V)), PAM were lavaged and analyzed for alterations in superoxide (O-2(-)), and tumor necrosis factor (TNF-alpha) production. There were no differences in bronchoalveolar lavage fluid TNF-alpha. PAM. lavaged from As(V)-exposed animals showed significant increases in O-2(-) production and in basal release of TNF-alpha. PAM lavaged from animals receiving As(III) did not show significant alterations. To test the direct effects of arsenic, PAM were lavaged from control animals and exposed to concentrations of 0,1 to 300 mu g/ml arsenic in vitro for up to 24 hr. Doses used were not cytotoxic to PAM, since LDH release was not significantly increased. Significant dose-dependent inhibition of O-2(-) production was only evident after 24 hr exposure to arsenicals. Both As(III) and As(V) produced inhibition at concentrations of 10 mu g/ml. Suppression of LPS-induced release of TNF-alpha also occurred at similar concentrations for both arsenicals (4-5 mu g/ml). Neither arsenical inhibited prostaglandin E(2) production. Measurement of soluble arsenic concentrations indicated dissolution of the compounds could not account for all of the effects seen. Arsenic-induced alteration in PAM function may compromise host defense.