Lung injury, inflammation and Akt signaling following inhalation of particulate hexavalent chromium.
Lung injury, inflammation and Akt signaling following inhalation of particulate hexavalent chromium.
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DOI：
10.1016/j.taap.2008.11.018
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发表时间：
2009-02-15
影响因子：
3.8
通讯作者：
Patierno SR
中科院分区：
文献类型：
--
作者：
Beaver LM;Stemmy EJ;Constant SL;Schwartz A;Little LG;Gigley JP;Chun G;Sugden KD;Ceryak SM;Patierno SR
某些颗粒状六价铬[Cr(VI)]化合物是人类呼吸道致癌物，会释放具有遗传毒性的可溶性铬酸盐，并与肺部的纤维化、纤维肉瘤、腺癌和鳞状细胞癌有关。我们推测炎症过程和介质可能有助于六价铬致癌的病因学研究，然而，接触颗粒状铬酸盐后即刻（0 - 24小时）的病理损伤和免疫反应尚未得到充分研究。我们的目的是确定BALB/c小鼠鼻内接触颗粒状碱式铬酸锌后肺部损伤的性质、炎症反应以及存活信号反应。在气道灌洗液和肺组织中测量了与肺部损伤、炎症和存活信号相关的因素。单次接触铬酸盐会在肺部引发急性免疫反应，其特征是白细胞介素 - 6（IL - 6）和生长调节致癌基因 - α（GRO - α）水平迅速且显著升高，中性粒细胞流入，以及肺气道中的巨噬细胞减少。对单次接触铬酸盐的动物的肺组织进行组织学检查发现，细支气管细胞凋亡和黏膜损伤增加。此外，铬酸盐暴露引起的损伤和炎症会发展为肺泡炎和间质性肺炎。最后，单次六价铬刺激导致气道中对存活信号蛋白Akt的丝氨酸473位点磷酸化具有免疫反应性的数量迅速且持续增加。这些数据表明，铬酸盐在肺部诱导存活信号和炎症反应，我们推测这可能有助于早期肿瘤发生。
Certain particulate hexavalent chromium [Cr(VI)] compounds are human respiratory carcinogens that release genotoxic soluble chromate, and are associated with fibrosis, fibrosarcomas, adenocarcinomas and squamous cell carcinomas of the lung. We postulate that inflammatory processes and mediators may contribute to the etiology of Cr(VI) carcinogenesis, however the immediate (0–24 hours) pathologic injury and immune responses after exposure to particulate chromates have not been adequately investigated. Our aim was to determine the nature of the lung injury, inflammatory response, and survival signaling responses following intranasal exposure of BALB/c mice to particulate basic zinc chromate. Factors associated with lung injury, inflammation and survival signaling were measured in airway lavage fluid and in lung tissue. A single chromate exposure induced an acute immune response in the lung, characterized by a rapid and significant increase in IL-6 and GRO-α levels, an influx of neutrophils, and a decline in macrophages in lung airways. Histological examination of lung tissue in animals challenged with a single chromate exposure revealed an increase in bronchiolar cell apoptosis and mucosal injury. Furthermore, chromate exposure induced injury and inflammation that progressed to alveolar and interstitial pneumonitis. Finally, a single Cr(VI) challenge resulted in a rapid and persistent increase in the number of airways immunoreactive for phosphorylation of the survival signaling protein Akt, on serine 473. These data illustrate that chromate induces both survival signaling and an inflammatory response in the lung, which we postulate may contribute to early oncogenesis.
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DOI：
10.1097/00043764-198001000-00008
发表时间：
1980-01-01
影响因子：
3.2
作者：
DALAGER, NA;MASON, TJ;PAYNE, WW
通讯作者：
PAYNE, WW
DOI：
10.1186/cc6101
发表时间：
2007
期刊：
Critical care (London, England)
影响因子：
--
作者：
Li LF;Liao SK;Lee CH;Huang CC;Quinn DA
通讯作者：
Quinn DA
影响因子：
3.3
作者：
Daniels, CE;Jett, JR
通讯作者：
Jett, JR
影响因子：
10.4
作者：
FISHBEIN, L
通讯作者：
FISHBEIN, L
影响因子：
5.5
作者：
Hansen, MB;Johansen, JD;Menné, T
通讯作者：
Menné, T