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The Proceedings of the American Thoracic Society 5:374 (2008)
© 2008 The American Thoracic Society
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Vascular Endothelial Growth Factor Is Essential for Maintaining Pulmonary Surfactant Protein D Expression In Vivo

Kechun Tang1, Jaret L. Malloy1 and Ellen C. Breen1

1 Division of Physiology, Department of Medicine, University of California, San Diego, La Jolla, California

Correspondence and requests for reprints should be addressed to Ellen C. Breen, Ph.D., Division of Physiology, Department of Medicine, University of California, 9500 Gilman Drive, San Diego, La Jolla, CA. E-mail: ebreen{at}ucsd.edu

The role of vascular endothelial growth factor (VEGF) to regulate surfactant homeostasis was investigated after gene inactivation of murine pulmonary VEGF in isolated type II cells and in vivo. VEGFLoxP type II cells incubated in vitro with cre recombinase adenovirus (Adv/Cre) demonstrated reduced VEGF levels from Days 2 to 5. In vitro VEGF-inactivated type II cells revealed a decrease in total phospholipid, disaturated phosphatidyl choline (DSPC), and DSPC synthesis compared with control uninfected or Adv/LacZ cells. Phorbol myristate acetate (PMA)-induced DSPC secretion was increased in Adv/Cre-infected cells. The levels of surfactant-associated proteins (SP)-B and -D, and the lipid transporters, ABCA1 and Rab3D, were also decreased in VEGF-deficient type II cells in vitro. These VEGF-dependent changes in surfactant metabolism were accompanied by a 425% increase in apoptotic cells compared with control type II cells. In contrast to these in vitro observations, lung-targeted VEGF gene deletion in vivo did not alter alveolar surfactant or tissue DSPC levels. Further, analysis of alveolar surfactant phospholipid composition revealed a decrease in sphingomyelin. In addition, SP-D expression was decreased in VEGF-deficient lungs. In vitro data suggest a role for VEGF in regulating type II cell surfactant metabolism and apoptosis. However, VEGF-deficient lungs in vivo are able to maintain surfactant phospholipid levels, but not SP-D expression.

FOOTNOTES

Supported by TRDRP 12RT-0062, NIH PO1 HL 17731-28 (Peter D. Wagner), and the Parker B. Francis Foundation.

Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

(Received in original form August 29, 2007; accepted in final form October 16, 2007)





This Article
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Right arrow Articles by Tang, K.
Right arrow Articles by Breen, E. C.
PubMed
Right arrow Articles by Tang, K.
Right arrow Articles by Breen, E. C.

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