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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Reversibility of pulmonary abnormalities by conditional replacement of surfactant protein D (SP-D) in vivo.

Surfactant protein D (SP-D) gene-targeted mice develop severe pulmonary disease associated with emphysema, pulmonary lipidosis, and foamy macrophage infiltrations. To determine the potential reversibility of these abnormalities, transgenic mice were developed in which SP-D was conditionally replaced in the respiratory epithelium of SP-D(-/-) mice. SP-D was not detected in the absence of doxycycline. Treatment with doxycycline after birth restored pulmonary SP-D concentrations and corrected pulmonary pathology at adulthood. When SP-D was replaced in adult SP-D(-/-) mice, alveolar SP-D was restored within 3 days, pulmonary lipid abnormalities were corrected, but emphysema persisted. In corrected adult SP-D(-/-) mice, loss of SP-D caused focal emphysema and pulmonary inflammation but did not cause phospholipid abnormalities characteristic of SP-D(-/-) mice. Thus, abnormalities in surfactant phospholipid homeostasis and alveolar macrophage abnormalities were readily corrected by restoration of SP-D. However, once established, emphysema was not reversed by SP-D. SP-D-dependent processes regulating surfactant lipid homeostasis were disassociated from those mediating emphysema.[1]


  1. Reversibility of pulmonary abnormalities by conditional replacement of surfactant protein D (SP-D) in vivo. Zhang, L., Ikegami, M., Dey, C.R., Korfhagen, T.R., Whitsett, J.A. J. Biol. Chem. (2002) [Pubmed]
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