Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.0107056 on November 5, 2007

Published online before print November 5, 2007
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(Journal of Leukocyte Biology. 2008;83:352-360.)
© 2008 by Society for Leukocyte Biology

Angiopoietin-mediated endothelial P-selectin translocation: cell signaling mechanisms

Ricardo Maliba, Alexandre Brkovic, Paul-Éduard Neagoe, Louis R. Villeneuve and Martin G. Sirois1

Montreal Heart Institute and Department of Pharmacology, Université de Montréal, Montreal, Québec, Canada

1 Correspondence: Montreal Heart Institute, 5000 Belanger Street, Montreal, QC, Canada, H1T 1C8. E-mail: martin.sirois{at}icm-mhi.org

Recently identified, angiopoietin-1 (Ang1) and -2 (Ang2) bind to the tyrosine kinase receptor Tie2 and contribute to orchestrate blood vessel formation during angiogenesis. Ang1 mediates vessel maturation and integrity by favoring the recruitment of pericytes and smooth muscle cells. Ang2, initially identified as a Tie2 antagonist, may under certain circumstances, induce Tie2 phosphorylation and biological activities. As inflammation exists in a mutually dependent association with angiogenesis, we sought to determine if Ang1 and/or Ang2 could modulate proinflammatory activities, namely P-selectin translocation, in bovine aortic endothelial cells (EC) and dissect the mechanisms implicated. P-selectin, an adhesion molecule found in the Weibel-Palade bodies of EC, is translocated rapidly to the cell surface upon EC activation during inflammatory processes. Herein, we report that Ang1 and Ang2 (1 nM) are capable of mediating a rapid Tie2 phosphorylation as well as a rapid and transient endothelial P-selectin translocation maximal within 7.5 min (125% and 100% increase, respectively, over control values). In addition, we demonstrate for the first time that angiopoietin-mediated endothelial P-selectin translocation is calcium-dependent and regulated through phospholipase C-{gamma} activation.

Key Words: Tie2 receptor • adhesion molecules • angiogenic factors






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