Sphingosine 1-phosphate effect on endothelial cell PAF synthesis: Role in cellular migration

• Published in: Journal of cellular biochemistry 2003-11, Vol.90 (4), p.719-731
• Main Authors: Bernatchez, Pascal N., Tremblay, François, Rollin, Simon, Neagoe, Paul-Eduard, Sirois, Martin G.
• Format: Article
• Language: English
• Subjects: Animals; Aorta - cytology; Aorta - drug effects; Aorta - metabolism; Cattle; Cell Movement - drug effects; Cells, Cultured; endothelial cells; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Enzyme Activation - drug effects; Humans; inflammatory mediators; Lysophospholipids - pharmacology; MAP kinases; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; phospholipases; Phospholipases A - antagonists & inhibitors; Phospholipases A - metabolism; Phosphorylation - drug effects; Platelet Activating Factor - biosynthesis; Platelet Activating Factor - metabolism; Platelet Membrane Glycoproteins - metabolism; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Receptors, G-Protein-Coupled - metabolism; Signal Transduction - drug effects; Sphingosine - analogs & derivatives; Sphingosine - pharmacology; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.10686

Sphingosine 1‐phosphate (S1P) and vascular endothelial growth factor (VEGF) are two inflammatory mediators capable of promoting endothelial cell (EC) migration and angiogenesis. As VEGF inflammatory effect is mediated by the synthesis of endothelial platelet‐activating factor (PAF) which is also contributing to VEGF chemotactic activity, we wanted to assess if S1P can trigger PAF synthesis in EC and if S1P‐induced migration is PAF‐dependent. Treatment of bovine aortic EC (BAEC) with S1P (10−10–10−6 M) increased dose‐ and time‐dependently the synthesis of PAF by up to 3.3‐fold above the basal level, with a maximal amount of PAF detected at 20 min post‐stimulation. This biological response was attenuated by inhibiting p38 mitogen‐activated protein kinase (MAPK), cytosolic or secreted phospholipase A2 (cPLA2, sPLA2) activity, suggesting that p38 MAPK activation by S1P promotes the conversion of membrane phospholipids into PAF through the combined activation of cPLA2 and sPLA2. Interestingly, pretreatment of BAEC with extracellular PAF receptor antagonists (BN52021, 10−5 M and CV3988, 10−6 M) reduced by up to 42% the cellular migration induced by S1P (10−6 M). These data demonstrate the capacity of S1P to induce PAF synthesis, which contributes in part to S1P chemotactic activity. © 2003 Wiley‐Liss, Inc.