Activation of endothelial cell phospholipase D by sphingosine and sphingosine-1-phosphate.

Natarajan, Viswanathan; Jayaram, Hiremagalur N.; Scribner, William M.; Garcia, Joe G.N.

doi:10.1165/ajrcmb.11.2.8049083

Cited by 72 publications

(52 citation statements)

References 35 publications

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“…Since our report of S1P-induced endothelial cell activation (16), there has been increasing evidence for a role of S1P in the maintenance and restoration of the dynamic semipermeable endothelial cellular barrier in the vasculature. S1P-mediated enhancement of endothelial junctional integrity via prominent cytoskeletal rearrangement involving the translocation of key actin-binding proteins, such as cortactin and myosin light chain kinase to the cell periphery and the formation of a strong cortical actin ring (3,5), has been defined.…”

Section: Discussionmentioning

confidence: 83%

Quantitative Proteomics Analysis of Human Endothelial Cell Membrane Rafts

Guo

Singleton

Rowshan

et al. 2007

Molecular & Cellular Proteomics

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Endothelial cell barrier dysfunction results in the increased vascular permeability observed in inflammation, tumor metastasis, angiogenesis, and atherosclerosis. Sphingosine 1-phosphate (S1P), a biologically active phosphorylated lipid growth factor released from activated platelets, enhances the endothelial cell barrier integrity in vitro and in vivo. To begin to identify the molecular mechanisms mediating S1P induced endothelial barrier enhancement, quantitative proteomics analysis (iTRAQ TM ) was performed on membrane rafts isolated from human pulmonary artery endothelial cells in the absence or presence of S1P stimulation. Our results demonstrated that S1P mediates rapid and specific recruitment (1 M, 5 min) of myristoylated alanine-rich protein kinase C substrate (MARCKS) and MARCKS-related protein (MRP) to membrane rafts. Western blot experiments confirmed these findings with both MARCKS and MRP. Finally, small interfering RNA-mediated silencing of MARCKS or MRP or both attenuates S1P-mediated endothelial cell barrier enhancement. These data suggest the regulation of S1P-mediated endothelial cell barrier enhancement via the cell specific localization of MARCKS and MRP and validate the utility of proteomics approaches in the identification of novel molecular targets. Molecular & Cellular Proteomics 6:689 -696, 2007.The pulmonary endothelium serves as a semipermeable cellular barrier between blood and the interstitium and airspaces of the lung. Endothelial cell (EC) 1 barrier dysfunction results in increased vascular permeability, which is a cardinal feature of inflammation and an essential component of tumor metastasis, angiogenesis, and atherosclerosis. Proteins and lipids released after platelet activation have long been appreciated as enhancing the integrity of the microcirculation (1, 2). Sphingosine 1-phosphate (S1P), a biologically active phosphorylated lipid growth factor released from platelet, has multiple EC effects, including promoting barrier integrity in vivo and in vitro across both human and bovine pulmonary artery and lung microvascular ECs (3, 4). Our previous studies demonstrated S1P mediated barrier enhancement to be dependent on S1P binding to its major surface receptor, S1P 1 ; activation of the small GTPase, Rac1; and rearrangement of the cortical actin cytoskeleton (3, 5, 6). Very recently, we further detailed the essential involvement of PI 3-kinase, Tiam1, and ␣-actinin in specialized membrane domains (i.e. membrane rafts) in S1P-treated EC barrier regulation (7). However, the underlying signaling mechanisms by which S1P increases vascular integrity via signaling to the endothelial cytoskeleton remain poorly understood.As defined by the recent Keystone Symposium on lipid rafts and cell function (March 23-28, 2006, in Steamboat Springs, CO) (8), "Membrane rafts are small (10 -200 nm), heterogeneous, highly dynamic, sterol-and sphingolipid-enriched domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protei...

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Section: Discussionmentioning

confidence: 83%

Quantitative Proteomics Analysis of Human Endothelial Cell Membrane Rafts

Guo

Singleton

Rowshan

et al. 2007

Molecular & Cellular Proteomics

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“…These observations clearly establish that the platelet, via soluble platelet-derived factors, is essential in maintaining normal vascular homeostasis. We and others have reported on vasoactive plateletderived lipids that activate endothelium, including our first report that S1P activated EC phospholipase D (7,10,23,33,48). Subsequent studies have since demonstrated that platelet-derived phospholipids modulate the barrier function of the vascular endothelium via both endothelial barrier-perturbing lipid products such as phosphatidate (6) and barrier-stabilizing/enhancing lipid products such as lysophosphatidic acid (LPA) (8,32) and S1P (11).…”

Section: Discussionmentioning

confidence: 86%

“…S1P is a normal constituent in plasma with increased (micromolar) levels in serum that are consistent with S1P release during whole blood coagulation (51). S1P exerts diverse biological effects on cells and is now recognized as an important courier of cellular information (7,10,23,33,48). S1P stimulates proliferation, calcium mobilization, adhesion molecule expression, and suppression of caspasedependent apoptosis (7,20,40,46) via ligation of G protein-coupled receptors of the EDG family (26).…”

Section: Discussionmentioning

confidence: 99%

Role of sphingosine-1 phosphate in the enhancement of endothelial barrier integrity by platelet-released products

Schaphorst

Chiang

Jacobs

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

165

152

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In vitro and in vivo evidence indicates that circulating platelets affect both vascular integrity and hemostasis. How platelets enhance the permeability barrier of the vascular endothelium is not well understood. We measured the effect of isolated human platelets on human pulmonary artery endothelial cell (EC) barrier integrity by monitoring transmonolayer electrical resistance. EC barrier function was significantly increased by the addition of platelets (ϳ40% maximum, 2.5 ϫ 10 6 platelets/ml). Platelet supernatants, derived from 2.5 ϫ 10 6 platelets/ml, reproduced the barrier enhancement and reversed the barrier dysfunction produced by the edemagenic agonist thrombin, which implicates a soluble barrier-promoting factor. The barrier-enhancing effect of platelet supernatants was heat stable but was attenuated by either charcoal delipidation (suggesting a vasoactive lipid mediator) or pertussis toxin, implying involvement of a G i␣-coupled receptor signal transduction pathway. Sphingosine-1-phosphate (S1P), a sphingolipid that is released from activated platelets, is known to ligate G protein-coupled EC differentiation gene (EDG) receptors, increase EC electrical resistance, and reorganize the actin cytoskeleton (Garcia JG, Liu F, Verin AD, Birukova A, Dechert MA, Gerthoffer WT, Bamberg JR, and English D. J Clin Invest 108: [689][690][691][692][693][694][695][696][697][698][699][700][701] 2001). Infection of EC with an adenoviral vector expressing an antisense oligonucleotide directed against EDG-1 but not infection with control vector attenuated the barrier-enhancing effect of both platelet supernatants and S1P. These results indicate that a major physiologically relevant vascular barrier-protective mediator produced by human platelets is S1P. endothelium; lung; vasculature; injury; G protein; differentiation; cell differentiating gene THE VASCULAR ENDOTHELIUM IS a biologically complex tissue that forms a semipermeable barrier between the intravascular fluid compartment and the interstitium of various organs. Integrity of the endothelial cell (EC) monolayer is essential for homeostasis, and perturbations of the barrier function of the endothelium are now recognized as a cardinal feature of diverse and important pathobiological processes including acute lung injury and atherogenesis. The lung vasculature contains an enormous surface area and is particularly sensitive to the dynamic features of endothelial barrier dysregulation, where increased vascular permeability leads to exudation of fluid and solutes from the intravascular space into the pulmonary interstitium. Extensive increases in lung vascular permeability result in flooding of the alveolar air spaces (pulmonary edema), which is the hallmark pathophysiological derangement of the adult respiratory distress syndrome. Circulating blood platelets have been noted for many decades to be essential to the maintenance of the endothelium as a semipermeable barrier. In vitro and in vivo models have described profound defects in EC barrier function after perfusion wit...

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“…The available data indicate that endothelial cell activation induced by TNF-␣ is mediated through the generation of sphingosine 1-phospate (S1P), and S1P is able to mimic the effect of TNF-␣ on endothelial cells (30). Because S1P-mediated IL-8 secretion relies on phospholipase D (PLD)-dependent ERK activation (5,16,28) and ceramide inhibits PLD activation (9,25), it is possible that ceramide inhibits ERK phosphorylation and IL-8 secretion through PLD inhibition.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Endothelial Interleukin-8 Production and Neutrophil Transmigration byStaphylococcus aureusBeta-Hemolysin

et al. 2009

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Neutrophils play a crucial role in the host response to infection with Staphylococcus aureus, which is a major human pathogen capable of causing life-threatening disease. Interleukin-8 (IL-8) is a potent chemoattractant and activator of neutrophils. We previously reported that S. aureus secretes a factor that suppresses IL-8 production by human endothelial cells. Here we isolated an inhibitor of IL-8 production from the supernatant and identified it as staphylococcal beta-hemolysin. Beta-hemolysin reduced IL-8 production without cytotoxicity to endothelial cells. Pretreatment with beta-hemolysin decreased the expression of both IL-8 mRNA and protein induced by tumor necrosis factor alpha (TNF-␣). Migration of neutrophils across TNF-␣-activated endothelium was also inhibited by beta-hemolysin. In contrast, beta-hemolysin had no effect on intercellular adhesive molecule 1 expression in activated endothelial cells. These results showed that beta-hemolysin produced by S. aureus interferes with inflammatory signaling in endothelial cells and may help S. aureus evade the host immune response.

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Activation of endothelial cell phospholipase D by sphingosine and sphingosine-1-phosphate.

Cited by 72 publications

References 35 publications

Quantitative Proteomics Analysis of Human Endothelial Cell Membrane Rafts

Quantitative Proteomics Analysis of Human Endothelial Cell Membrane Rafts

Role of sphingosine-1 phosphate in the enhancement of endothelial barrier integrity by platelet-released products

Inhibition of Endothelial Interleukin-8 Production and Neutrophil Transmigration byStaphylococcus aureusBeta-Hemolysin

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