背景:气候变化和人类活动已经摧毁了全世界的湖泊。大盐湖里的水,犹他州,美国处于创纪录的低点附近,这增加了暴露于干燥的湖床沉积物中风吹的灰尘的风险。尽管人们认为灰尘是有害的,但尚未进行评估吸入大盐湖灰尘(GSLD)对健康影响的正式研究。这项研究的目的是说明风吹的灰尘事件,评估吸入的灰尘对肺部的影响,并确定可能导致GSLD在肺部影响的机制。结果:动画,每小时粒子和气象数据,和图像说明了沙尘事件对盐湖谷/瓦萨奇正面气流的影响。大盐湖沉积物和PM2.5含有金属,脂多糖,天然和人为化学物质,和细菌。吸入和口咽递送PM2.5引发的中性粒细胞增多和Il6,Cxcl1的mRNA表达,Cxcl2和Muc5ac在小鼠肺中,比粉煤灰(CFA)PM2.5更有效,并且在体外对人气道上皮细胞(HBEC3-KT)具有更大的细胞毒性。使用HBEC3-KT和THP-1细胞在体外复制IL6和IL8的诱导。对于HBEC3-KT细胞,IL6诱导被EGTA/钌红可变地减弱,TLR4抑制剂TAK-242和去铁胺,而IL8被EGTA/钌红减弱。EGTA/钌红对mRNA诱导的抑制表明过渡金属的作用,钙,和钙通道作为反应的介质。像CFA,GSLD和来自加利福尼亚索尔顿海的类似尘埃,激活的人TRPA1、M8和V1。然而,在HBEC3-KT细胞中,仅抑制TRPV1、TRPV3和两种通道的组合影响细胞因子mRNA的诱导。与TRP通道相反,THP1细胞的反应部分由TLR4介导,当通过吸入暴露于GSLD时,表达TRPV1“人源化”形式的小鼠表现出更大的嗜中性粒细胞。结论:这项研究表明,来自大盐湖和类似湖泊沉积物的风尘可能会通过包括TRPV1/V3,TLR4激活以及可能的氧化应激在内的机制对人类构成风险。
UNASSIGNED: Climatological shifts and human activities have decimated lakes worldwide. Water in the Great Salt Lake, Utah, USA is at near record lows which has increased risks for exposure to windblown
dust from dried lakebed sediments. Formal studies evaluating the health effects of inhaled Great Salt Lake
dust (GSLD) have not been performed despite the belief that the
dust is harmful. The objectives of this study were to illustrate windblown
dust events, assess the impact of inhaled
dust on the lungs, and to identify mechanisms that could contribute to the effects of GSLD in the lungs.
UNASSIGNED: An animation, hourly particle and meteorological data, and images illustrate the impact of dust events on the Salt Lake Valley/Wasatch front airshed. Great Salt Lake sediment and PM2.5 contained metals, lipopolysaccharides, natural and anthropogenic chemicals, and bacteria. Inhalation and oropharyngeal delivery of PM2.5 triggered neutrophilia and the expression of mRNA for Il6, Cxcl1, Cxcl2, and Muc5ac in mouse lungs, was more potent than coal fly ash (CFA) PM2.5, and more cytotoxic to human airway epithelial cells (HBEC3-KT) in vitro. Induction of IL6 and IL8 was replicated in vitro using HBEC3-KT and THP-1 cells. For HBEC3-KT cells, IL6 induction was variably attenuated by EGTA/ruthenium red, the TLR4 inhibitor TAK-242, and deferoxamine, while IL8 was attenuated by EGTA/ruthenium red. Inhibition of mRNA induction by EGTA/ruthenium red suggested roles for transition metals, calcium, and calcium channels as mediators of the responses. Like CFA, GSLD and a similar dust from the Salton Sea in California, activated human TRPA1, M8, and V1. However, only inhibition of TRPV1, TRPV3, and a combination of both channels impacted cytokine mRNA induction in HBEC3-KT cells. Responses of THP1 cells were partially mediated by TLR4 as opposed to TRP channels and mice expressing a \"humanized\" form of TRPV1 exhibited greater neutrophilia when exposed to GSLD via inhalation.
UNASSIGNED: This study suggests that windblown
dust from Great Salt Lake and similar lake sediments could pose a risk to humans via mechanisms including the activation of TRPV1/V3, TLR4, and possibly oxidative stress.