Lung inflammation, injury, and proliferative response after repetitive particulate hexavalent chromium exposure.
Lung inflammation, injury, and proliferative response after repetitive particulate hexavalent chromium exposure.
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DOI：
10.1289/ehp.0900715
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发表时间：
2009-12
影响因子：
10.4
通讯作者：
Patierno SR
中科院分区：
文献类型：
--
作者：
Beaver LM;Stemmy EJ;Schwartz AM;Damsker JM;Constant SL;Ceryak SM;Patierno SR
慢性炎症与包括肺癌在内的多种人类癌症的发生有关。某些颗粒状六价铬[Cr(VI)]化合物是有充分证据的人类呼吸道致癌物，它们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、腺癌和鳞状细胞癌相关。尽管如此，对于反复接触颗粒状铬酸盐后的病理损伤和免疫反应却知之甚少。
在这项研究中，我们研究了反复接触颗粒状铬酸盐后的肺部损伤、炎症、增殖以及存活信号反应。
使用鼻内暴露方案，用颗粒状碱式铬酸锌或生理盐水对BALB/c小鼠进行反复处理。我们通过支气管肺泡灌洗、组织学检查和免疫组织化学评估了肺部因Cr(VI)诱导的变化。
单次接触Cr(VI)会导致肺组织炎症，这种炎症可持续长达21天。每次处理后24小时，反复接触Cr(VI)会诱导中性粒细胞性气道炎症反应。在处理后5天，中性粒细胞随后被数量不断增加的巨噬细胞所取代。反复接触Cr(VI)会诱导慢性支气管周围炎症，伴有以淋巴细胞和巨噬细胞为主的肺泡炎和间质性肺炎。此外，观察到慢性毒性黏膜损伤，并伴有气道基质金属蛋白酶 - 9前体增加。损伤和炎症与气道对存活信号蛋白Akt的磷酸化和增殖标记物Ki - 67产生免疫反应相关。我们在接触铬酸盐的动物的气道内衬上皮细胞中观察到一种反应性增殖反应。
这些数据表明，反复接触颗粒状铬酸盐会诱导慢性损伤和一种可能促进Cr(VI)致癌作用的炎症微环境。
Chronic inflammation is implicated in the development of several human cancers, including lung cancer. Certain particulate hexavalent chromium [Cr(VI)] compounds are well-documented human respiratory carcinogens that release genotoxic soluble chromate and are associated with fibrosis, fibrosarcomas, adenocarcinomas, and squamous cell carcinomas of the lung. Despite this, little is known about the pathologic injury and immune responses after repetitive exposure to particulate chromates. In this study we investigated the lung injury, inflammation, proliferation, and survival signaling responses after repetitive exposure to particulate chromate. BALB/c mice were repetitively treated with particulate basic zinc chromate or saline using an intranasal exposure regimen. We assessed lungs for Cr(VI)-induced changes by bronchoalveolar lavage, histologic examination, and immunohistochemistry. Single exposure to Cr(VI) resulted in inflammation of lung tissue that persists for up to 21 days. Repetitive Cr(VI) exposure induced a neutrophilic inflammatory airway response 24 hr after each treatment. Neutrophils were subsequently replaced by increasing numbers of macrophages by 5 days after treatment. Repetitive Cr(VI) exposure induced chronic peribronchial inflammation with alveolar and interstitial pneumonitis dominated by lymphocytes and macrophages. Moreover, chronic toxic mucosal injury was observed and accompanied by increased airway pro-matrix metalloprotease-9. Injury and inflammation correlated with airways becoming immunoreactive for phosphorylation of the survival signaling protein Akt and the proliferation marker Ki-67. We observed a reactive proliferative response in epithelial cells lining airways of chromate-exposed animals. These data illustrate that repetitive exposure to particulate chromate induces chronic injury and an inflammatory microenvironment that may promote Cr(VI) carcinogenesis.
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影响因子：
3.8
作者：
O'Hara, KA;Klei, LR;Barchowsky, A
通讯作者：
Barchowsky, A
影响因子：
3.8
作者：
Beaver LM;Stemmy EJ;Constant SL;Schwartz A;Little LG;Gigley JP;Chun G;Sugden KD;Ceryak SM;Patierno SR
通讯作者：
Patierno SR
影响因子：
10.4
作者：
FISHBEIN, L
通讯作者：
FISHBEIN, L
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：
3.8
作者：
Cohen, MD;Zelikoff, JT;Schlesinger, RB
通讯作者：
Schlesinger, RB