Reaction products of hexamethylene diisocyanate vapors with "self" molecules in the airways of rabbits exposed via tracheostomy.
Reaction products of hexamethylene diisocyanate vapors with "self" molecules in the airways of rabbits exposed via tracheostomy.
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DOI：
10.1080/00498254.2017.1329569
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Nassar AF
中科院分区：
文献类型：
--
作者：
Wisnewski AV;Kanyo J;Asher J;Goodrich JA;Barnett G;Patrylak L;Liu J;Redlich CA;Nassar AF
六亚甲基二异氰酸酯(HDI)是一种广泛使用的脂肪族二异氰酸酯，也是公认的职业性哮喘的原因。下呼吸道中的“自身”分子(多肽/蛋白质)，容易与HDI发生化学反应，已被假设在哮喘发病机制和/或化学代谢中发挥作用，但仍缺乏特征。这项研究采用了独特的方法来识别和表征下呼吸道HDI反应性的“自我”靶标。麻醉兔通过气管切开管自由呼吸，连接到装有O2或O2加~200 ppb HDI蒸气的房间。暴露60分钟后，对呼吸道进行冲洗，并用LC-MS和LC-MS/MS对液体进行分析。暴露于低分子量(<；3 kDa)HDI而不是对照的兔支气管肺泡灌洗液鉴定出783.26和476.18 m/z[M+H]+离子，其高能碰撞诱导解离(HCD)模式与双谷胱甘肽-HDI和单(GSH)-HDI一致。对暴露的兔BAL液的高分子量(>；3 kDa)部分进行的蛋白质组学分析表明，HDI修饰了子宫球蛋白(又名Clara细胞蛋白)和白蛋白中的特定赖氨酸。综上所述，这项研究利用了一种独特的方法在兔体内暴露化学气体，以确定HDI反应产物与下呼吸道中的“自身”分子。
Hexamethylenediisocyanate (HDI) is a widely used aliphatic diisocyanate and a well-recognized cause of occupational asthma. “Self” molecules (peptides/proteins) in the lower airways, susceptible to chemical reactivity with HDI, have been hypothesized to play a role in asthma pathogenesis and/or chemical metabolism, but remain poorly characterized. This study employed unique approaches to identify and characterize “self” targets of HDI reactivity in the lower airways. Anesthetized rabbits free breathed through a tracheostomy tube connected to chambers containing either, O2, or O2 plus ~200 ppb HDI vapors. Following 60 minutes of exposure, the airways were lavaged and the fluid was analyzed by LC-MS and LC-MS/MS. The low-molecular weight (<3 kDa) fraction of HDI exposed, but not control rabbit bronchoalveolar lavage (BAL) fluid identified 783.26 and 476.18 m/z [M+H]+ ions with high energy collision-induced dissociation (HCD) fragmentation patterns consistent with bis glutathione (GSH)-HDI and mono(GSH)-HDI. Proteomic analyses of the high molecular weight (>3 kDa) fraction of exposed rabbit BAL fluid identified HDI modification of specific lysines in uteroglobin (aka clara cell protein) and albumin. In summary, this study utilized a unique approach to chemical vapor exposure in rabbits, to identify HDI reaction products with “self” molecules in the lower airways.
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影响因子：
6.1
作者：
KENNEDY, AL;WILSON, TR;BROWN, WE
通讯作者：
BROWN, WE
影响因子：
--
作者：
Fent, Kenneth W.;Gaines, Linda G. Trelles;Nylander-French, Leena A.
通讯作者：
Nylander-French, Leena A.
影响因子：
3.4
作者：
Kültz D;Li J;Sacchi R;Morin D;Buckpitt A;Van Winkle L
通讯作者：
Van Winkle L
影响因子：
1.8
作者：
Gledhill, A;Wake, A;Shiotsuka, R
通讯作者：
Shiotsuka, R
影响因子：
1.5
作者：
Harkema, Jack R.;Carey, Stephan A.;Wagner, James G.
通讯作者：
Wagner, James G.