Editors' ChoiceAcute Lung Injury

When Too Much Oxygen Is Not Too Much

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Science Translational Medicine  20 Oct 2010:
Vol. 2, Issue 54, pp. 54ec161
DOI: 10.1126/scitranslmed.3001789

Oxygen therapy is a common and effective way to prevent organ and tissue damage in patients with various lung and heart disorders. However, prolonged treatment with high concentrations of oxygen may damage the lungs, causing hyperoxic acute lung injury (HALI). Premature newborns are often treated with supplemental oxygen because of respiratory problems in their underdeveloped lungs, but the consequent lung injury—HALI—in some may cause bronchopulmonary dysplasia (BPD). BPD is often fatal because of lack of specific diagnostic markers and intervention strategies. Now, Sohn et al. demonstrate that breast regression protein-39 (BRP-39) modulates antioxidant response and could play a role in the pathogenesis of HALI.

BRP-39 is a glycoprotein that is expressed during mammary gland involution in the mouse. Increased expression of BRP-39 and its human homolog YKL-40 has been associated with lung diseases such as asthma and chronic obstructive pulmonary disease (COPD); however, their physiological function was unknown. The authors demonstrated that hyperoxia decreased expression of BRP-39 and YKL-40 in mouse lungs and human bronchial epithelial cells, respectively. They then investigated hyperoxia-induced toxicity in BRP-39–deficient mice. Hyperoxic exposure caused premature death in BRP-39–deficient mice that could be attributed to enhanced lung injury and was ameliorated by lack of caspase-3. The human homolog YKL-40 mitigated hyperoxia-induced lung injury, increasing survival in BRP-39–deficient mice. Moreover, in tracheal aspirates of premature infants suffering from respiratory distress syndrome (RDS) and treated with hyperoxia, amounts of YKL-40 were lower in infants that subsequently experienced complications than in those that did not. These studies indicate a regulatory role for BRP-39 and YKL-40 in mice and human HALI, respectively. These authors have previously shown a correlation between increased lung tissue levels of YKL-40 and compromised lung function and asthma severity. Therefore, maintenance of physiological levels of these proteins could be critical in the prevention of acute lung injury and subsequent chronic lung disease.

M. H. Sohn et al., The chitinase-like proteins breast regression protein-39 and YKL-40 regulate hyperoxia-induced acute lung injury. Am. J. Respir. Crit. Care. Med. 182, 918–928 (2010). [Abstract]

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