Hemopexin Reverses Activation of Lung eIF2a and Decreases Mitochondrial Injury in Chlorine Exposed Mice

Am J Physiol Lung Cell Mol Physiol. 2023 Dec 27. doi: 10.1152/ajplung.00273.2023. Online ahead of print.ABSTRACTWe assessed the mechanisms by which non-encapsulated heme, released in the plasma of mice post exposure to chlorine (Cl2) gas, resulted in the initiation and propagation of acute lung injury. We exposed adult male and female C57BL/6 mice to Cl2 (500 ppm for 30 min), returned them to room air, and injected them intramuscularly with either human hemopexin (hHPX; 5 µg/ g BW in 50 µl saline) or vehicle at 1h post exposure. Upon return to room air, Cl2 exposed mice, injected with vehicle, developed respiratory acidosis, increased concentrations of plasma proteins in the alveolar space, lung mitochondrial DNA injury, increased levels of free plasma heme and major alterations of their lung proteome. hHPX injection mice mitigated the onset and development of lung and mitochondrial injury and the increase of plasma heme, reversed the Cl2 induced changes in eighty-three of 237 proteins in the lung proteome at 24 h post exposure, and improved survival at 15 d post-exposure. System biology analysis of the lung global proteomics data showed that hHPX reversed changes of a number of key pathways including elF2 signaling, verified by western blotting measurements. Recombinant human hemopexin, generated in tobacco plants, injected at 1h post Cl2 exposure, was equally effective in reversing acute lung and mtDNA injury. The results of this study offer new insights as to the mechani...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Source Type: research