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细颗粒和超细颗粒硫酸气溶胶对豚鼠的影响:肺泡巨噬细胞功能和细胞内pH值的改变。

Effects of fine and ultrafine sulfuric acid aerosols in guinea pigs: alterations in alveolar macrophage function and intracellular pH.

作者信息

Chen L C, Fine J M, Qu Q S, Amdur M O, Gordon T

机构信息

Institute of Environmental Medicine, New York University Medical Center, Tuxedo 10987.

出版信息

Toxicol Appl Pharmacol. 1992 Mar;113(1):109-17. doi: 10.1016/0041-008x(92)90014-j.

Abstract

Acidic sulfate is the most toxicologically important sulfur oxide which exists in the ambient air. To determine if particle size influences toxic effects of sulfuric acid, we investigated the effects of sulfuric acid aerosols of two different sizes on biochemical and cellular parameters of bronchoalveolar lavage fluid from exposed guinea pigs. Guinea pigs were exposed to fine (mass median diameter, 0.3 micron), and ultrafine (mass median diameter, 0.04 micron) sulfuric acid aerosols at 300 micrograms/m3 for 3 hr/day. The animals were euthanized immediately and 24 hr after 1 and 4 days of exposure and lungs were lavaged. Elevated beta-glucuronidase, lactate dehydrogenase activities, and total protein concentration as well as decreased cell viability were observed in the lavage after a single exposure to sulfuric acid aerosols of both sizes. These alterations were small, though statistically significant, and transient. No alteration in these parameters was observed after 4 days of exposure to acid aerosols. In contrast, sulfuric acid-induced alterations in alveolar macrophage function were more pronounced and longer lasting. Immediately after a single exposure to fine acid, there was a 2.7-fold increase in the spontaneous tumor necrosis factor (TNF) release over that in the control group while endotoxin-stimulated TNF release was increased by 2.2-fold. In addition, acid aerosols of both sizes increased the TNF release from macrophages after 4 days of exposure, although there was no clear temporal pattern of induction or recovery. Furthermore, immediately after 4 days of exposure to either fine or ultrafine acid, the amount of H2O2 that could be induced from baseline production by alveolar macrophages was 2.2-fold higher than that of the controls. The phagocytic function of macrophages was also altered by exposure to sulfuric acid aerosols. Twenty-four hours after single or multiple exposure, fine acid enhanced (as high as 78% above control) the in vitro phagocytic activity of alveolar macrophages while ultrafine acid depressed the phagocytic capacity (as much as 50% below that in the control). In addition to these biochemical parameters and cellular functions, we also measured the intracellular pH (pHi) of macrophages harvested after exposures to these acid aerosols using a pH-sensitive fluorescent dye. The resting pHi was depressed after a single exposure to both acid aerosols. The depression in pHi persisted 24 hr after ultrafine acid exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

酸性硫酸盐是存在于环境空气中毒理学意义最为重要的硫氧化物。为了确定粒径是否会影响硫酸的毒性作用,我们研究了两种不同粒径的硫酸气溶胶对暴露的豚鼠支气管肺泡灌洗液的生化和细胞参数的影响。豚鼠暴露于质量中值直径为0.3微米的细颗粒和质量中值直径为0.04微米的超细颗粒硫酸气溶胶中,浓度为300微克/立方米,每天暴露3小时。在暴露1天和4天后立即以及暴露24小时后对动物实施安乐死,并对肺部进行灌洗。单次暴露于两种粒径的硫酸气溶胶后,灌洗液中β-葡萄糖醛酸酶、乳酸脱氢酶活性以及总蛋白浓度升高,细胞活力降低。这些改变虽小,但具有统计学意义且是短暂的。暴露于酸性气溶胶4天后,这些参数未观察到变化。相比之下,硫酸引起的肺泡巨噬细胞功能改变更为明显且持续时间更长。单次暴露于细颗粒酸后,自发肿瘤坏死因子(TNF)释放量比对照组增加了2.7倍,而内毒素刺激的TNF释放量增加了2.2倍。此外,两种粒径的酸性气溶胶在暴露4天后均增加了巨噬细胞的TNF释放,尽管诱导或恢复没有明显的时间模式。此外,在暴露于细颗粒或超细颗粒酸4天后,肺泡巨噬细胞从基线产生的过氧化氢量立即比对照组高2.2倍。巨噬细胞的吞噬功能也因暴露于硫酸气溶胶而改变。单次或多次暴露24小时后,细颗粒酸增强了肺泡巨噬细胞的体外吞噬活性(比对照组高78%),而超细颗粒酸则降低了吞噬能力(比对照组低50%)。除了这些生化参数和细胞功能外,我们还使用对pH敏感的荧光染料测量了暴露于这些酸性气溶胶后收获的巨噬细胞的细胞内pH(pHi)。单次暴露于两种酸性气溶胶后,静息pHi降低。超细颗粒酸暴露后,pHi降低持续24小时。(摘要截短至400字)

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