American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Sep 2011
Comparative StudyLy6Chi monocytes direct alternatively activated profibrotic macrophage regulation of lung fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a devastating disease. Antiinflammatory therapies, including corticosteroids, are of no benefit. The role of monocytes and macrophages is therefore controversial. ⋯ We demonstrate the importance of circulating monocytes and lung macrophages during pulmonary fibrosis, and emphasize the importance of the alternatively activated macrophage phenotype. We show that Ly6Chi monocytes facilitate the progression of pulmonary fibrosis, but are not obviously engrafted into lungs thereafter. Finally, we provide empirical data to suggest that macrophages may have a resolution-promoting role during the reversible phase of bleomycin-induced pulmonary fibrosis.
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Am. J. Respir. Crit. Care Med. · Sep 2011
Comparative StudyInhibiting lung elastase activity enables lung growth in mechanically ventilated newborn mice.
Mechanical ventilation with O₂-rich gas (MV-O₂) offers life-saving treatment for respiratory failure, but also promotes lung injury. We previously reported that MV-O2 of newborn mice increased lung elastase activity, causing elastin degradation and redistribution of elastic fibers from septal tips to alveolar walls. These changes were associated with transforming growth factor (TGF)-β activation and increased apoptosis leading to defective alveolarization and lung growth arrest, as seen in neonatal chronic lung disease. ⋯ Intratracheal elafin, by blocking lung protease activity, prevented MV-O₂-induced elastin degradation, TGF-β activation, apoptosis, and dispersion of matrix elastin, and attenuated lung structural abnormalities noted in vehicle-treated mice after 24 hours of MV-O₂. These findings suggest that elastin breakdown contributes to defective lung growth in response to MV-O₂ and might be targeted therapeutically to prevent MV-O₂-induced lung injury.
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Am. J. Respir. Crit. Care Med. · Sep 2011
ReviewCurrent controversies and future perspectives in chronic obstructive pulmonary disease.
Over the past decade there has been much research and interest in COPD. As a result, the understanding and management of the disease has improved significantly. Yet, there are many uncertainties and controversies that require further work. This review discusses these controversies and anticipates some of the changes that may occur in the near future in the field of COPD.