title: Angiopoietin-2 exocytosis is stimulated by sphingosine-1-phosphate in human blood and lymphatic endothelial cells.
abstract: OBJECTIVE
  Although diverse functions of angiopoietin-2 (Ang2) have been revealed, little is known about upstream signaling molecules regulating Ang2 exocytosis. We therefore investigated the mechanism of Ang2 exocytosis in human blood and lymphatic endothelial cells (BECs and LECs) by stimulation with sphingosine-1-phosphate (S1P).
  
  
  RESULTS
  By immunostaining and ELISA analyses using our newly developed human Ang2-specific antibodies, Ang2 exocytosis from human endothelial cells was examined. Both exogenous and endogenous S1P trigger rapid Ang2 exocytosis in time- and dose-dependent manners. Intriguingly, S1P-induced Ang2 exocytosis is higher in LECs than BECs. These effects of S1P are mainly mediated by the endothelial differentiation gene receptor 1, which subsequently activates its downstream phospholipase C and intracellular calcium mobilization to trigger Ang2 exocytosis. Consistently, S1P also dramatically stimulates Ang2 exocytosis from the ECs of ex vivo-incubated blood vessels.
  
  
  CONCLUSIONS
  These results imply that the rapid secretion of Ang2 by exocytosis from endothelial cells is another possible mechanism underlying S1P-induced angiogenesis and inflammation.
authors.affiliation: National Research Laboratory for Vascular Biology and Department of Biological Sciences, KAIST, Daejeon, Republic of Korea.
authors.forename: Cholsoon
authors.initials: C
authors.lastname: Jang
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Koh
authors.forename: Nam Kyu
authors.initials: NK
authors.lastname: Lim
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kang
authors.forename: Duk Hoon
authors.initials: DH
authors.lastname: Kim
authors.forename: Sung Kwang
authors.initials: SK
authors.lastname: Park
authors.forename: Gyun Min
authors.initials: GM
authors.lastname: Lee
authors.forename: Choon Ju
authors.initials: CJ
authors.lastname: Jeon
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Koh
mesh_terms: D042702:Angiopoietin-2 / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004729:Endothelium, Lymphatic / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005089:Exocytosis / Q000187:drug effects; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D049349:Receptors, Lysosphingolipid / Q000037:antagonists & inhibitors / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D014470:Umbilical Cord / Q000098:blood supply
chemical_list: D042702:Angiopoietin-2; D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; D014409:Tumor Necrosis Factor-alpha; C060506:sphingosine 1-phosphate; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D013110:Sphingosine