Cell-free hemoglobin: a novel mediator of acute lung injury

American Journal of Physiology. Lung Cellular and Molecular Physiology
Ciara M ShaverJulie A Bastarache

Abstract

Patients with the acute respiratory distress syndrome (ARDS) have elevated levels of cell-free hemoglobin (CFH) in the air space, but the contribution of CFH to the pathogenesis of acute lung injury is unknown. In the present study, we demonstrate that levels of CFH in the air space correlate with measures of alveolar-capillary barrier dysfunction in humans with ARDS (r = 0.89, P < 0.001) and in mice with ventilator-induced acute lung injury (r = 0.89, P < 0.001). To investigate the specific contribution of CFH to ARDS, we studied the impact of purified CFH in the mouse lung and on cultured mouse lung epithelial (MLE-12) cells. Intratracheal delivery of CFH in mice causes acute lung injury with air space inflammation and alveolar-capillary barrier disruption. Similarly, in MLE-12 cells, CFH increases proinflammatory cytokine expression and increases paracellular permeability as measured by electrical cell-substrate impedance sensing. Next, to determine whether these effects are mediated by the iron-containing heme moiety of CFH, we treated mice with intratracheal hemin, the chloride salt of heme, and found that hemin was sufficient to increase alveolar permeability but failed to induce proinflammatory cytokine expression or epi...Continue Reading

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Citations

Jan 26, 2018·JCI Insight·Ciara M ShaverUNKNOWN Lung Transplant Outcomes Group (LTOG)
Jul 20, 2018·American Journal of Physiology. Lung Cellular and Molecular Physiology·Aleksandra LeligdowiczMichael A Matthay
Aug 21, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Amit Gaggar, Rakesh P Patel
Jul 19, 2019·Experimental and Therapeutic Medicine·Teiji OdaKen-Ichi Matsumoto
Dec 12, 2020·Intensive Care Medicine Experimental·Sean E GillUNKNOWN Lawson COVID19 Study Team
Dec 10, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Mark J McVeyNeil M Goldenberg
Nov 1, 2020·Physiological Reports·Ciara M ShaverJulie A Bastarache
Feb 11, 2021·MBio·Shivang S ShahAlice S Prince
Jan 17, 2021·The Journal of Thoracic and Cardiovascular Surgery·Betty PatUNKNOWN Clinical Working Group
Feb 16, 2021·Frontiers in Immunology·Oluwabukola T GbotoshoGregory J Kato
Jun 27, 2020·Trends in Molecular Medicine·Paul W BuehlerDominik J Schaer
Jun 3, 2021·International Journal of Molecular Sciences·Stefan W Ryter
May 30, 2021·The European Respiratory Journal·Israr AhmadSadis Matalon

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