| First Author | Anyanwu AC | Year | 2014 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 306 |
| Issue | 8 | Pages | L749-63 |
| PubMed ID | 24532288 | Mgi Jnum | J:210272 |
| Mgi Id | MGI:5569886 | Doi | 10.1152/ajplung.00236.2013 |
| Citation | Anyanwu AC, et al. (2014) Suppression of inflammatory cell trafficking and alveolar simplification by the heme oxygenase-1 product carbon monoxide. Am J Physiol Lung Cell Mol Physiol 306(8):L749-63 |
| abstractText | Bronchopulmonary dysplasia (BPD), a lung disease of prematurely born infants, is characterized in part by arrested development of pulmonary alveolae. We hypothesized that heme oxygenase (HO-1) and its byproduct carbon monoxide (CO), which are thought to be cytoprotective against redox stress, mitigate lung injury and alveolar simplification in hyperoxia-exposed neonatal mice, a model of BPD. Three-day-old C57BL/6J mice were exposed to air or hyperoxia (FiO2, 75%) in the presence or absence of inhaled CO (250 ppm for 1 h twice daily) for 21 days. Hyperoxic exposure increased mean linear intercept, a measure of alveolar simplification, whereas CO treatment attenuated hypoalveolarization, yielding a normal-appearing lung. Conversely, HO-1-null mice showed exaggerated hyperoxia-induced hypoalveolarization. CO also inhibited hyperoxia-induced pulmonary accumulation of F4/80+, CD11c+, and CD11b+ monocytes and Gr-1+ neutrophils. Furthermore, CO attenuated lung mRNA and protein expression of proinflammatory cytokines, including the monocyte chemoattractant CCL2 in vivo, and decreased hyperoxia-induced type I alveolar epithelial cell CCL2 production in vitro. Hyperoxia-exposed CCL2-null mice, like CO-treated mice, showed attenuated alveolar simplification and lung infiltration of CD11b+ monocytes, consistent with the notion that CO blocks lung epithelial cell cytokine production. We conclude that, in hyperoxia-exposed neonatal mice, inhalation of CO suppresses inflammation and alveolar simplification. |
