Loss of PECAM-1 function impairs alveolarization

Horace M. DeLisser, Brian P. Helmke, Gaoyuan Cao, Patricia M. Egan, Darren Taichman, Melane Fehrenbach, Aisha Zaman, Zheng Cui, Gopi S. Mohan, H. Scott Baldwin, Peter F. Davies, Rashmin C. Savani

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

The final stage of lung development in humans and rodents occurs principally after birth and involves the partitioning of the large primary saccules into smaller air spaces by the inward protrusion of septae derived from the walls of the saccules. Several observations in animal models implicate angiogenesis as critical to this process of alveolarization, but all anti-angiogenic treatments examined to date have resulted in endothelial cell (EC) death. We therefore targeted the function of platelet endothelial cell adhesion molecule, (PECAM-1), an EC surface molecule that promotes EC migration and has been implicated in in vivo angiogenesis. Administration of an anti-PECAM-1 antibody that inhibits EC migration, but not proliferation or survival in vitro, disrupted normal alveolar septation in neonatal rat pups without reducing EC content. Three-dimensional reconstruction of lungs showed that pups treated with a blocking PECAM-1 antibody had remodeling of more proximal branches resulting in large tubular airways. Subsequent studies in PECAM-1-null mice confirmed that the absence of PECAM-1 impaired murine alveolarization, without affecting EC content, proliferation, or survival. Further, cell migration was reduced in lung endothelial cells isolated from these mice. These data suggest that the loss of PECAM-1 function compromises postnatal lung development and provide evidence that inhibition of EC function, in contrast to a loss of viable EC, inhibits alveolarization.

Original languageEnglish (US)
Pages (from-to)8724-8731
Number of pages8
JournalJournal of Biological Chemistry
Volume281
Issue number13
DOIs
StatePublished - Mar 31 2006

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    DeLisser, H. M., Helmke, B. P., Cao, G., Egan, P. M., Taichman, D., Fehrenbach, M., Zaman, A., Cui, Z., Mohan, G. S., Baldwin, H. S., Davies, P. F., & Savani, R. C. (2006). Loss of PECAM-1 function impairs alveolarization. Journal of Biological Chemistry, 281(13), 8724-8731. https://doi.org/10.1074/jbc.M511798200