Angiopoietin-2 exocytosis is stimulated by sphingosine-1-phosphate in human blood and lymphatic endothelial cells.
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.
Jang
Cholsoon
C
National Research Laboratory for Vascular Biology and Department of Biological Sciences, KAIST, Daejeon, Republic of Korea.
Koh
Young Jun
YJ
Lim
Nam Kyu
NK
Kang
Hyun Jung
HJ
Kim
Duk Hoon
DH
Park
Sung Kwang
SK
Lee
Gyun Min
GM
Jeon
Choon Ju
CJ
Koh
Gou Young
GY
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
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