Loss of PECAM-1 function impairs alveolarization.

DeLisser HM, Helmke BP, Cao G, Egan PM, Taichman D, Fehrenbach M, Zaman A, Cui Z, Mohan GS, Baldwin HS, Davies PF, Savani RC
J Biol Chem. 2006 281 (13): 8724-31

PMID: 16377626 · DOI:10.1074/jbc.M511798200

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.

MeSH Terms (21)

Animals Anti-Inflammatory Agents Antibodies, Blocking Antibodies, Monoclonal Apoptosis Cell Culture Techniques Cell Movement Cell Proliferation Cells, Cultured Dexamethasone Endothelium, Vascular Immunohistochemistry Injections, Intraperitoneal Lung Mice Mice, Knockout Platelet Endothelial Cell Adhesion Molecule-1 Pulmonary Alveoli Rats Rats, Sprague-Dawley Receptor, TIE-1

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