Heme Attenuation Ameliorates Irritant Gas Inhalation-Induced Acute Lung Injury

血红素衰减改善刺激性气体吸入引起的急性肺损伤

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作者:Saurabh Aggarwal, Adam Lam, Subhashini Bolisetty, Matthew A Carlisle, Amie Traylor, Anupam Agarwal, Sadis Matalon

Aims

Exposure to irritant gases, such as bromine (Br2), poses an environmental and occupational hazard that

Conclusion

The data suggest that attenuating heme may prove to be a useful adjuvant therapy to treat patients with ALI.

Results

C57BL/6 mice were exposed to Br2 gas (600 ppm, 30 min) and returned to room air. Thirty minutes postexposure, mice were injected intraperitoneally with a single dose of the heme scavenging protein, hemopexin (Hx) (3 μg/gm body weight), or saline. Twenty-four hours postexposure, saline-treated mice had elevated total heme in bronchoalveolar lavage fluid (BALF) and plasma and acute lung injury (ALI) culminating in 80% mortality after 10 days. Hx treatment significantly lowered heme, decreased evidence of ALI (lower protein and inflammatory cells in BALF, lower lung wet-to-dry weight ratios, and decreased airway hyperreactivity to methacholine), and reduced mortality. In addition, Br2 caused more severe ALI and mortality in mice with HO-1 gene deletion (HO-1-/-) compared to wild-type controls, while transgenic mice overexpressing the human HO-1 gene (hHO-1) showed significant protection. Innovation: This is the first study delineating the role of heme in ALI caused by Br2.

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