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Am J Physiol Lung Cell Mol Physiol (December 3, 2004). doi:10.1152/ajplung.00142.2004
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Submitted on April 15, 2004
Accepted on November 10, 2004

Surfactant Protein-D Influences Surfactant Ultrastructure and Uptake by Alveolar Type II Cells

Machiko Ikegami1*, Cheng-Lun Na1, Thomas R. Korfhagen1, and Jeffrey A. Whitsett1

1 Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio, USA; University of Cincinnati Medical School, Cincinnati, Ohio, USA

* To whom correspondence should be addressed. E-mail: machiko.ikegami{at}cchmc.org.

Surfactant Protein D (SP-D) is a member of the collectin family of the innate host defense proteins. In the lung, SP-D is expressed primarily by type II cells. Gene targeted SP-D deficient (SP-D(-/-))mice have 3-5 fold higher surfactant lipid pool sizes. However, surfactant synthesis and secretion by type II cells and its catabolism by alveolar macrophages are normal in SP-D(-/-)mice. Therefore, we hypothesized that SP-D might regulate surfactant homeostasis by influencing surfactant structure, thereby altering its uptake by type II cells. Large (LA) and small aggregate surfactant (SA) were isolated from bronchoalveolar lavage fluid (BALF) from SP-D(-/-), SP-D(+/+)and transgenic mice in which SP-D was expressed under conditional control of doxycycline in alveolar type II cells. Uptake of both LA and SA isolated from SP-D(-/-) mice by normal type II cells was decreased. Abnormally dense lipid forms were observed by electronmicroscopy of LA from SP-D(-/-)mice. SA from SP-D(-/-) mice consisted of atypical multi-lamellated small vesicles. Abnormalities in surfactant uptake by type II cells and in surfactant ultrastructure were corrected by conditional expression of SP-D in vivo. Pre-incubation of BALF from SP-D(-/-)mice with SP-D changed surfactant ultrastructure to be similar to that of SP-D(+/+) mice in vitro. The rapid changes in surfactant structure, increased uptake by type II cells and decreased pool sizes normally occurring in the postal period were not seen in SPManus/ SPDUUT D(-/-) mice. SP-D regulates uptake and catabolism by type II cells and influences the ultrastructure of surfactant in the alveolus.




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