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First published online November 26, 2007
doi: 10.1242/10.1242/dev.012187

Development 134, 4449-4458 (2007)
Published by The Company of Biologists 2007
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Obligatory participation of macrophages in an angiopoietin 2-mediated cell death switch

Sujata Rao1, Ivan B. Lobov1,*, Jefferson E. Vallance1, Kaoru Tsujikawa2, Ichiro Shiojima3, Shailaja Akunuru4, Kenneth Walsh3, Laura E. Benjamin2 and Richard A. Lang1,{dagger}

1 Division of Pediatric Ophthalmology, Division of Developmental Biology, Children's Hospital Research Foundation and Department of Ophthalmology, University of Cincinnati, Cincinnati, OH 45229, USA.
2 Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
3 Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston MA 02118, USA.
4 Graduate Program of Molecular and Developmental Biology, College of Medicine, University of Cincinnati, Cincinnati, OH45229, USA.

{dagger} Author for correspondence (e-mail: richard.lang{at}cchmc.org)

Accepted 23 September 2007

Macrophages have a critical function in the recognition and engulfment of dead cells. In some settings, macrophages also actively signal programmed cell death. Here we show that during developmentally scheduled vascular regression, resident macrophages are an obligatory participant in a signaling switch that favors death over survival. This switch occurs when the signaling ligand angiopoietin 2 has the dual effect of suppressing survival signaling in vascular endothelial cells (VECs) and stimulating Wnt ligand production by macrophages. In response to the Wnt ligand, VECs enter the cell cycle and in the absence of survival signals, die from G1 phase of the cell cycle. We propose that this mechanism represents an adaptation to ensure that the macrophage and its disposal capability are on hand when cell death occurs.

Key words: Macrophage, Angiopoietin, Wnt, Programmed cell death, Vascular regression, Cell cycle


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