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Angiopoietin‐mediated endothelial P‐selectin translocation: cell signaling mechanisms
Author(s) -
Maliba Ricardo,
Brkovic Alexandre,
Neagoe PaulÉduard,
Villeneuve Louis R.,
Sirois Martin G.
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0107056
Subject(s) - angiopoietin receptor , biology , angiogenesis , angiopoietin , microbiology and biotechnology , phosphorylation , endothelial stem cell , p selectin , receptor tyrosine kinase , tyrosine phosphorylation , chromosomal translocation , inflammation , immunology , cancer research , biochemistry , vascular endothelial growth factor , platelet activation , in vitro , platelet , gene , vegf receptors
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‐γ activation.