Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine.
Superfund Research Center, University of Alabama at Birmingham, Birmingham, Alabama.
Am J Respir Cell Mol Biol. 2023 May;68(5):485-497. doi: 10.1165/rcmb.2022-0321MA.
Organoarsenicals, such as lewisite and related chloroarsine, diphenylchloroarsine (DPCA), are chemical warfare agents developed during World War I. Stockpiles in Eastern Europe remain a threat to humans. The well-documented effects of cutaneous exposure to these organoarsenicals include skin blisters, painful burns, and life-threatening conditions such as acute respiratory distress syndrome. In survivors, long-term effects such as the development of respiratory ailments are reported for the organoarsenical sulfur mustard; however, no long-term pulmonary effects are documented for lewisite and DPCA. No animal models exist to explore the relationship between skin exposure to vesicants and constrictive bronchiolitis. We developed and characterized a mouse model to study the long-term effects of cutaneous exposure on the lungs after exposure to a sublethal dose of organoarsenicals. We exposed mice to lewisite, DPCA, or a less toxic surrogate organoarsenic chemical, phenyl arsine oxide, on the skin. The surviving mice were followed for 20 weeks after skin exposure to arsenicals. Lung microcomputed tomography, lung function, and histology demonstrated increased airway resistance, increased thickness of the smooth muscle layer, increased collagen deposition in the subepithelium, and peribronchial lymphocyte infiltration in mice exposed to arsenical on skin.
有机胂化物，如路易氏剂和相关的氯胂，二苯基氯胂（DPCA），是第一次世界大战期间开发的化学战剂。东欧的库存仍然对人类构成威胁。这些有机胂化物经皮肤接触的有据可查的影响包括皮肤水疱、疼痛性烧伤和急性呼吸窘迫综合征等危及生命的情况。在幸存者中，据报道，有机胂硫芥会导致呼吸道疾病等长期影响；然而，路易氏剂和 DPCA 没有记录到长期的肺部影响。没有动物模型可以探索皮肤暴露于糜烂性毒剂与缩窄性细支气管炎之间的关系。我们开发并表征了一种小鼠模型，以研究皮肤暴露于亚致死剂量的有机胂化物后对肺部的长期影响。我们将小鼠暴露于皮肤中的路易氏剂、DPCA 或毒性较低的替代有机砷化学物质苯胂化氧。在皮肤暴露于砷剂后，幸存的小鼠被跟踪 20 周。肺部微计算机断层扫描、肺功能和组织学显示，暴露于砷剂的小鼠气道阻力增加、平滑肌层厚度增加、上皮下胶原沉积增加以及细支气管周围淋巴细胞浸润。
