TY - JOUR
T1 - Sphingosine 1-phosphate activates Weibel-Palade body exocytosis
AU - Matsushita, Kenji
AU - Morrell, Craig N.
AU - Lowenstein, Charles J.
PY - 2004/8/3
Y1 - 2004/8/3
N2 - Sphingosine 1-phosphate (S1P) not only regulates angiogenesis, vascular permeability and vascular tone, but it also promotes vascular inflammation. However, the molecular basis for the proinflammatory effects of S1P is not understood. We now show that S1P activates endothelial cell exocytosis of Weibel-Palade bodies, releasing vasoactive substances capable of causing vascular thrombosis and inflammation. S1P triggers endothelial exocytosis in part through phospholipase C-γ signal transduction. However, S1P also modulates endothelial cell exocytosis by activating endothelial nitric oxide synthase production of nitric oxide, which inhibits exocytosis. Thus S1P plays a dual role in regulating endothelial exocytosis, triggering pathways that both promote and inhibit endothelial exocytosis. Regulation of endothelial exocytosis may explain part of the proinflammatory effects of S1P.
AB - Sphingosine 1-phosphate (S1P) not only regulates angiogenesis, vascular permeability and vascular tone, but it also promotes vascular inflammation. However, the molecular basis for the proinflammatory effects of S1P is not understood. We now show that S1P activates endothelial cell exocytosis of Weibel-Palade bodies, releasing vasoactive substances capable of causing vascular thrombosis and inflammation. S1P triggers endothelial exocytosis in part through phospholipase C-γ signal transduction. However, S1P also modulates endothelial cell exocytosis by activating endothelial nitric oxide synthase production of nitric oxide, which inhibits exocytosis. Thus S1P plays a dual role in regulating endothelial exocytosis, triggering pathways that both promote and inhibit endothelial exocytosis. Regulation of endothelial exocytosis may explain part of the proinflammatory effects of S1P.
KW - Ceramide
KW - Endothelial
KW - Nitric oxide
KW - Von Willebrand factor
UR - http://www.scopus.com/inward/record.url?scp=3843054498&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3843054498&partnerID=8YFLogxK
U2 - 10.1073/pnas.0400185101
DO - 10.1073/pnas.0400185101
M3 - Article
C2 - 15273282
AN - SCOPUS:3843054498
SN - 0027-8424
VL - 101
SP - 11483
EP - 11487
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 31
ER -