Antigen-induced Ca2+ mobilization in RBL-2H3 cells: Role of I(1,4,5)P3 and S1P and necessity of I(1,4,5)P3 production

Lee, Hyun Sil; Park, Chang Shin; Lee, Young Mi; Suk, Ho Young; Clemons, Tameka C.M.; Choi, Oksoon Hong

doi:10.1016/j.ceca.2005.08.002

Cited by 28 publications

(34 citation statements)

References 52 publications

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“…SphK2 was found to be an intrinsic regulator of mast cell calcium influx and responses, whereas SphK1 appears to be important in regulating the levels of circulating S1P and thus extrinsically affecting mast cell responsiveness. This is conflicting with the previous suggestions that SphK1 is the key isoform in mast cells (in experiments that used pharmacological inhibitors or siRNA silencing strategies), because its activity has been implicated in calcium responses in the RBL-2H3 mast cell line and in human mast cells (Lee et al, 2005a;Melendez and Khaw, 2002). However, our view is supported by several lines of evidence.…”

Section: Discussioncontrasting

confidence: 82%

“…While the detailed mechanism by which SphK2 regulates calcium mobilization remains to be fully explored, it should be noted that unlike a previous suggestion (Lee et al, 2005a), we uncovered no evidence of a role for SphKs or S1P in mobilizing calcium from ER stores. Intracellular S1P formation has been reported to promote calcium-induced calcium entry in human neutrophils (Itagaki and Hauser, 2003) and calcium influx in yeast (Birchwood et al, 2001).…”

Section: Discussioncontrasting

confidence: 65%

“…In contrast, S1P 2 contributes to the robustness of the mast cell degranulation response (Jolly et al, 2004). S1P has also been suggested as an important regulator of calcium mobilization in mast cells, through an unknown mechanism that is seemingly independent of S1P receptors (Choi et al, 1996;Lee et al, 2005a;Melendez and Khaw, 2002). The balance of SPH to S1P has also been implicated as a rheostat that controls the mast cells responsiveness to a stimulus (Prieschl et al, 1999).…”

Section: Introductionmentioning

confidence: 89%

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The Sphingosine Kinase-Sphingosine-1-Phosphate Axis Is a Determinant of Mast Cell Function and Anaphylaxis

et al. 2007

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Sphingosine-1-phosphate, a key mediator in immune cell trafficking, is elevated in the lungs of asthmatic patients and regulates pulmonary epithelium permeability. Stimulation of mast cells by allergens induces two mammalian sphingosine kinases (Sphk1 and Sphk2) to produce sphingosine-1-phosphate (S1P). Little is known about the individual role of these kinases in regulating immune cell function. Here we show that in mast cells, Sphk2 is required for production of S1P, for calcium influx, for activation of protein kinase C, and for cytokine production and degranulation. However, susceptibility to in vivo anaphylaxis is determined both by S1P within the mast cell compartment and by circulating S1P generated by Sphk1 predominantly from a non-mast cell source(s). Thus, sphingosine kinases are determinants of mast cell responsiveness, demonstrating a previously unrecognized relationship with anaphylaxis.

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Section: Discussioncontrasting

confidence: 82%

Section: Discussioncontrasting

confidence: 65%

Section: Introductionmentioning

confidence: 89%

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The Sphingosine Kinase-Sphingosine-1-Phosphate Axis Is a Determinant of Mast Cell Function and Anaphylaxis

et al. 2007

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“…Five GPCRs with alternative functions have been described for S1P and these have been designated S1P 1-5 [46]. In addition to acting through these cell surface receptors to modify cellular function, S1P may also act intracellularly to mobilize intracellular calcium and such a mechanism may contribute, in part, to the calcium signal observed in activated mast cell [47,48]. Mast cells express both the S1P 1 and S1P 2 receptors [43,45].…”

Section: Sphingosine-1-phosphatementioning

confidence: 99%

G protein-coupled receptors and the modification of FcɛRI-mediated mast cell activation

2007

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By releasing multiple pro-inflammatory mediators upon activation, mast cells are critical effector cells in the pathogenesis of allergic inflammation. The traditional viewpoint of antigen-dependent mast cell activation is that of a Th 2 -driven process whereby antigen-specific IgE molecules are produced by B cells followed by binding of the IgE to high affinity IgE receptors (FcεRI) expressed on mast cells. Subsequent antigen-dependent aggregation of the FcεRI initiates an intracellular signalling cascade that culminates in mediator release. Mast cell responses, including cell growth, survival, chemotaxis, and cell adhesion, however, can also be regulated by other receptors expressed on mast cells. Furthermore, FcεRI-mediated mast cell mediator release can be significantly modified by ligation of specific classes of these receptors. One such class of receptors is the G protein-coupled receptors (GPCR). In this review, we describe how sub-populations of GPCRs can either enhance or inhibit FcεRI-mediated mast cell activation depending on the particular G protein utilized for relaying signalling. Furthermore, we discuss the potential mechanisms whereby the signalling responses utilized by the FcεRI for mast cell activation are influenced by those initiated by GPCRs to produce these diverse responses. KeywordsMast cells; FcεRI; G protein-coupled receptors; IgE; antigen; signalling Mast cell activationMast cells play a role in both the innate and adaptive immune responses which contribute to the body's defence mechanisms against invading pathogens and parasites [1][2][3]. However, when mast cells are inappropriately activated following antigen exposure, the resulting release of multiple pro-inflammatory mediators leads to the initiation of the clinical manifestations associated with allergic inflammation [4]. This response occurs as a consequence of the antigen binding to IgE molecules which occupy high affinity receptors for IgE (FcεRI) on the mast cell surface and resulting cross-linking of these receptors [5,6]. FcεRI aggregation induces a cascade of intracellular signalling events which lead to the rapid release of histamine and proteolytic enzymes, as a consequence of degranulation, and the release of leukotrienes (LTs) and prostaglandins (PGs), as a result of phospholipase A 2 (PLA 2 )-mediated phospholipid hydrolysis [4,7]. Following enhanced gene expression, a variety of cytokines and chemokines * To whom correspondence be addressed: agilfillan@niaid.nih.gov, Bldg 10, Room 11C206, LAD, NIAID, NIH, 10 Center Drive, Bethesda, USA, MD 20892-1881, Phone: 301 496 8757, Fax: 301 480 8384. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the...

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“…PAO was previously shown to effectively inhibit antigenstimulated PI turnover, providing evidence for its capacity to inhibit IP 3 -dependent Ca 21 release from stores (Adamczewski et al, 1992 (Lee et al, 2005). Fig.…”

Section: Resultsmentioning

confidence: 87%

Inhibitors of PI(4,5)P₂Synthesis Reveal Dynamic Regulation of IgE Receptor Signaling by Phosphoinositides in RBL Mast Cells

et al. 2013

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Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2 ) is a versatile phospholipid that participates in many membrane-associated signaling processes. PI(4,5)P 2 production at the plasma membrane (PM) depends on levels of its precursor, phosphatidylinositol 4-phosphate (PI4P), synthesized principally by two intracellular enzymes, PI4-kinases IIIa and IIIb; the former is preferentially inhibited by phenylarsine oxide (PAO). We found that PAO and quercetin, another lipid kinase inhibitor, rapidly inhibit Ca 21 responses to antigen in IgE-sensitized rat basophilic leukemia mast cells. Quercetin also rapidly inhibits store-operated Ca 21 influx stimulated by thapsigargin. In addition, quercetin and PAO effectively inhibit antigen-stimulated ruffling and spreading in these cells, and they inhibit endocytosis of crosslinked IgE receptor complexes, evidently by inhibiting pinching off of endocytic vesicles containing the clustered IgE receptors. A minimal model to account for these diverse effects is inhibition of PI(4,5)P 2 synthesis by PAO and quercetin. To characterize the direct effects of these agents on PI(4,5)P 2 synthesis, we monitored the reappearance of the PI(4,5)P 2 -specific PH domain PH-phospholipase C d-EGFP at the PM after Ca 21 ionophore (A23187)-induced PI(4,5)P 2 hydrolysis, followed by Ca 21 chelation with excess EGTA. Resynthesized PI(4,5)P 2 initially appears as micron-sized patches near the PM. Addition of quercetin subsequent to A23187-induced PI(4,5)P 2 hydrolysis reduces PI(4,5)P 2 resynthesis in PM-associated patches, and PAO reduces PI(4,5)P 2 at the PM while enhancing PI(4,5)P 2 accumulation at the Golgi complex. Taken together, these results provide evidence that PI4P generated by PI4-kinase IIIa is dynamically coupled to PI(4,5)P

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Antigen-induced Ca2+ mobilization in RBL-2H3 cells: Role of I(1,4,5)P3 and S1P and necessity of I(1,4,5)P3 production

Cited by 28 publications

References 52 publications

The Sphingosine Kinase-Sphingosine-1-Phosphate Axis Is a Determinant of Mast Cell Function and Anaphylaxis

The Sphingosine Kinase-Sphingosine-1-Phosphate Axis Is a Determinant of Mast Cell Function and Anaphylaxis

G protein-coupled receptors and the modification of FcɛRI-mediated mast cell activation

Inhibitors of PI(4,5)P₂Synthesis Reveal Dynamic Regulation of IgE Receptor Signaling by Phosphoinositides in RBL Mast Cells

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Antigen-induced Ca2+ mobilization in RBL-2H3 cells: Role of I(1,4,5)P3 and S1P and necessity of I(1,4,5)P3 production

Cited by 28 publications

References 52 publications

The Sphingosine Kinase-Sphingosine-1-Phosphate Axis Is a Determinant of Mast Cell Function and Anaphylaxis

The Sphingosine Kinase-Sphingosine-1-Phosphate Axis Is a Determinant of Mast Cell Function and Anaphylaxis

G protein-coupled receptors and the modification of FcɛRI-mediated mast cell activation

Inhibitors of PI(4,5)P2Synthesis Reveal Dynamic Regulation of IgE Receptor Signaling by Phosphoinositides in RBL Mast Cells

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Product

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Inhibitors of PI(4,5)P₂Synthesis Reveal Dynamic Regulation of IgE Receptor Signaling by Phosphoinositides in RBL Mast Cells