Obligatory participation of macrophages in an angiopoietin 2-mediated cell death switch.
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.
Rao
Sujata
S
Division of Pediatric Ophthalmology, Children's Hospital Research Foundation, University of Cincinnati, Cincinnati, OH 45229, USA.
Lobov
Ivan B
IB
Vallance
Jefferson E
JE
Tsujikawa
Kaoru
K
Shiojima
Ichiro
I
Akunuru
Shailaja
S
Walsh
Kenneth
K
Benjamin
Laura E
LE
Lang
Richard A
RA
D042702:Angiopoietin-2 / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002453:Cell Cycle; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology; D008024:Ligands; D008264:Macrophages / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism
D042702:Angiopoietin-2; D008024:Ligands; D051153:Wnt Proteins; D042787:Receptor, TIE-2; D051057:Proto-Oncogene Proteins c-akt