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1 Division of Pulmonary Biolgoy, Cincinnati Children's Hospital Medical Center and The University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
* To whom correspondence should be addressed. E-mail: machiko.ikegami{at}cchmc.org.
While decreased concentrations of SP-B are associated with lung injury and respiratory distress, potential causal relationships between SP-B deficiency and lung inflammation remain unclear. A transgenic mouse in which human SP-B expression was placed under conditional control of doxycycline via the CCSP promoter, was utilized to determine the role of SP-B in the initiation of pulmonary inflammation. Adult mice, made SP-B deficient by removal of doxycycline, developed severe respiratory failure within four days. Deficiency of SP-B was associated with increased minimal surface tension of the surfactant and perturbed lung mechanics. Four days of SP-B deficiency did not alter SP-C content or surfactant phospholipid content or composition. SP-B deficiency was associated with lung inflammation and increased sL-selectin, STAT-3 and pSTAT-3 in alveolar macrophages and alveolar epithelial cells. Alveolar IL-6, IL-1
and MIP-2 concentrations were increased after removal of doxycycline indicating pulmonary inflammation. Restoration of SP-B expression following administration of doxycycline rapidly reversed SP-B dependent abnormalities in lung mechanics and inflammation. SP-B deficiency is sufficient to cause lung dysfunction and inflammation in adult mice. SP-B reversed inflammation and maintained lung function in vivo, indicating its potential utility for the prevention and treatment of pulmonary injury and surfactant deficiency.
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