Cutaneous lewisite exposure causes acute lung injury,Annals of the New York Academy of Sciences

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Cutaneous lewisite exposure causes acute lung injury
Annals of the New York Academy of Sciences ( IF 4.1 ) Pub Date : 2020-04-24 , DOI: 10.1111/nyas.14346
Shajer Manzoor ₁ , Nithya Mariappan ₁ , Iram Zafar ₁ , Chih-Chang Wei ₁ , Aamir Ahmad ₁ , Ranu Surolia ₂ , Jeremy B Foote ₂ , Anupam Agarwal ₂ , Shama Ahmad ₁ , Mohammad Athar ₃ , Veena B Antony ₂ , Aftab Ahmad ₁

Affiliation

Lewisite is a strong vesicating and chemical warfare agent. Because of the rapid transdermal absorption, cutaneous exposure to lewisite can also elicit severe systemic injury. Lewisite (2.5, 5.0, and 7.5 mg/kg) was applied to the skin of Ptch1+/−/SKH‐1 mice and acute lung injury (ALI) was assessed after 24 hours. Arterial blood gas measurements showed hypercapnia and hypoxemia in the lewisite‐exposed group. Histological evaluation of lung tissue revealed increased levels of proinflammatory neutrophils and a dose‐dependent increase in structural changes indicative of injury. Increased inflammation was also confirmed by altered expression of cytokines, including increased IL‐33, and a dose‐dependent elevation of CXCL1, CXCL5, and GCSF was observed in the lung tissue. In the bronchoalveolar lavage fluid of lewisite‐exposed animals, there was a significant increase in HMGB1, a damage‐associated molecular pattern molecule, as well as elevated CXCL1 and CXCL5, which coincided with an influx of neutrophils to the lungs. Complete blood cell analysis revealed eosinophilia and altered neutrophil–lymphocyte ratios as a consequence of lewisite exposure. Mean platelet volume and RBC distribution width, which are predictors of lung injury, were also increased in the lewisite group. These data demonstrate that cutaneous lewisite exposure causes ALI and may contribute to mortality in exposed populations.

中文翻译：

皮肤路易斯暴露导致急性肺损伤

路易斯石是一种强起泡剂和化学战剂。由于快速透皮吸收，皮肤暴露于路易斯也可引起严重的全身损伤。将 Lewisite（2.5、5.0 和 7.5 mg/kg）应用于 Ptch1+/-/SKH-1 小鼠的皮肤，并在 24 小时后评估急性肺损伤 (ALI)。动脉血气测量显示路易斯暴露组出现高碳酸血症和低氧血症。肺组织的组织学评估显示促炎性中性粒细胞水平增加，并且指示损伤的结构变化呈剂量依赖性增加。炎症增加也通过细胞因子表达的改变得到证实，包括增加的 IL-33，并且在肺组织中观察到 CXCL1、CXCL5 和 GCSF 的剂量依赖性升高。在路易斯暴露动物的支气管肺泡灌洗液中，HMGB1（一种与损伤相关的分子模式分子）显着增加，以及 CXCL1 和 CXCL5 升高，这与中性粒细胞流入肺部相吻合。完整的血细胞分析显示，由于路易斯暴露，嗜酸性粒细胞增多和中性粒细胞-淋巴细胞比率改变。路易斯组的平均血小板体积和红细胞分布宽度是肺损伤的预测指标。这些数据表明，皮肤路易氏体暴露会导致 ALI，并可能导致暴露人群的死亡率。完整的血细胞分析显示，由于路易斯暴露，嗜酸性粒细胞增多和中性粒细胞-淋巴细胞比率改变。路易斯组的平均血小板体积和红细胞分布宽度是肺损伤的预测指标。这些数据表明，皮肤路易氏体暴露会导致 ALI，并可能导致暴露人群的死亡率。完整的血细胞分析显示，由于路易斯暴露，嗜酸性粒细胞增多和中性粒细胞-淋巴细胞比率改变。路易斯组的平均血小板体积和红细胞分布宽度是肺损伤的预测指标。这些数据表明，皮肤路易氏体暴露会导致 ALI，并可能导致暴露人群的死亡率。

更新日期：2020-04-24

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