Chlorine (Cl2) and bromine (Br2) are produced in large quantities throughout the world and used in the industry and the sanitation of water. These halogens can pose a significant threat to public health when released into the atmosphere during transportation and industrial accidents, or as acts of terrorism. In this review, we discuss the evidence showing that the activity of Cl2 and Br2, and of products formed by their interaction with biomolecules, fragment high‐molecular‐weight hyaluronan (HMW‐HA), a key component of the interstitial space and present in epithelial cells, to form proinflammatory, low‐molecular‐weight hyaluronan fragments that increase intracellular calcium (Ca2+) and activate RAS homolog family member A (RhoA) in airway smooth muscle and epithelial and microvascular cells. These changes result in airway hyperresponsiveness (AHR) to methacholine and increase epithelial and microvascular permeability. The increase in intracellular Ca2+ is the result of the activation of the calcium‐sensing receptor by Cl2, Br2, and their by‐products. Posthalogen administration of a commercially available form of HMW‐HA to mice and to airway cells in vitro reverses the increase of Ca2+ and the activation of RhoA, and restores AHR to near‐normal levels of airway function. These data have established the potential of HMW‐HA to be a countermeasure against Cl2 and Br2 toxicity.

中文翻译：

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透明质酸和卤素诱导的气道高反应性和肺损伤

氯 (Cl2) 和溴 (Br2) 在世界各地大量生产，用于工业和水的卫生。这些卤素在运输和工业事故期间释放到大气中或作为恐怖主义行为时，会对公众健康构成重大威胁。在这篇综述中，我们讨论了证据表明 Cl2 和 Br2 的活性，以及​​它们与生物分子、碎片高分子量透明质酸 (HMW-HA) 的相互作用形成的活性，后者是间隙空间的关键成分，存在于上皮细胞，形成促炎、低分子量透明质酸片段，增加细胞内钙 (Ca2+) 并激活气道平滑肌和上皮细胞和微血管细胞中的 RAS 同源家族成员 A (RhoA)。这些变化导致气道对乙酰甲胆碱的高反应性 (AHR) 并增加上皮和微血管通透性。细胞内 Ca2+ 的增加是 Cl2、Br2 及其副产物激活钙敏感受体的结果。在体外向小鼠和气道细胞施用一种市售形式的 HMW-HA 后卤素给药可逆转 Ca2+ 的增加和 RhoA 的激活，并将 AHR 恢复到接近正常水平的气道功能。这些数据确定了 HMW-HA 作为对抗 Cl2 和 Br2 毒性的对策的潜力。在体外向小鼠和气道细胞施用一种市售形式的 HMW-HA 后卤素给药可逆转 Ca2+ 的增加和 RhoA 的激活，并将 AHR 恢复到接近正常水平的气道功能。这些数据确定了 HMW-HA 作为对抗 Cl2 和 Br2 毒性的对策的潜力。在体外向小鼠和气道细胞施用一种市售形式的 HMW-HA 后卤素给药可逆转 Ca2+ 的增加和 RhoA 的激活，并将 AHR 恢复到接近正常水平的气道功能。这些数据确定了 HMW-HA 作为对抗 Cl2 和 Br2 毒性的对策的潜力。