Research Topics
Genomes and Genes
| Alasdair M GilfillanSummaryAffiliation: National Institutes of Health Country: USA Publications
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Detail Information
Publications
Regulation of mast cell responses in health and diseaseAlasdair M Gilfillan
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1881, USA
Crit Rev Immunol 31:475-529. 2011....- Mast cell biology: introduction and overviewAlasdair M Gilfillan
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
Adv Exp Med Biol 716:2-12. 2011..This introductory chapter outlines and highlights the various topics of mast cell biology that will be discussed in further detail in subsequent chapters... 
Integrated signalling pathways for mast-cell activationAlasdair M Gilfillan
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11C206, 10 Center Drive, MSC 1881, Bethesda, Maryland 20892 1881, USA
Nat Rev Immunol 6:218-30. 2006....- Kit- and Fc epsilonRI-induced differential phosphorylation of the transmembrane adaptor molecule NTAL/LAB/LAT2 allows flexibility in its scaffolding function in mast cellsShoko Iwaki
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, MSC 1881, Bethesda, MD 20892 1881, USA
Cell Signal 20:195-205. 2008..The observations reported herein support the conclusion that NTAL may be differentially utilized by specific receptors for relaying alternative signals and this suggests a flexibility in the function of TRAPs not previously appreciated... - The phosphoinositide 3-kinase-dependent activation of Btk is required for optimal eicosanoid production and generation of reactive oxygen species in antigen-stimulated mast cellsHye Sun Kuehn
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 181:7706-12. 2008..These data demonstrate that strategies to decrease mast cell production of ROS and eicosanoids would have to target both ERK1/2- and PI3K/Btk-dependent pathways... - Synergistic activation of phospholipases Cgamma and Cbeta: a novel mechanism for PI3K-independent enhancement of FcepsilonRI-induced mast cell mediator releaseHye Sun Kuehn
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive MSC 1881, Bethesda, MD 20892 1881, USA
Cell Signal 20:625-36. 2008..These responses were critical for the promotion of degranulation. This is the first report of synergistic activation between PLCgamma and PLCbeta that permits reinforcement of signals for degranulation in mast cells... - Stem cell factor programs the mast cell activation phenotypeTomonobu Ito
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 188:5428-37. 2012.... - Btk plays a crucial role in the amplification of Fc epsilonRI-mediated mast cell activation by kitShoko Iwaki
Laboratory of Allergic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892 1881, USA
J Biol Chem 280:40261-70. 2005..These data demonstrate, for the first time, that Btk is a key regulator of a Kit-mediated amplification pathway that augments Fc epsilonRI-mediated mast cell activation... - NTAL phosphorylation is a pivotal link between the signaling cascades leading to human mast cell degranulation following Kit activation and Fc epsilon RI aggregationChristine Tkaczyk
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Blood 104:207-14. 2004..NTAL, thus, appears to be an important link between the signaling pathways that are initiated by these receptors, culminating in mast cell degranulation... - Btk-dependent Rac activation and actin rearrangement following FcepsilonRI aggregation promotes enhanced chemotactic responses of mast cellsHye Sun Kuehn
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive MSC 1881, Bethesda, MD 20892 1881, USA
J Cell Sci 123:2576-85. 2010..Taken together, these data demonstrate that, by regulating signaling pathways that control F-actin rearrangement, Btk is crucial for the ability of antigen to amplify mast-cell chemotactic responses... - mTORC1 and mTORC2 differentially regulate homeostasis of neoplastic and non-neoplastic human mast cellsDaniel Smrz
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1881, USA
Blood 118:6803-13. 2011.... - RGS13 controls g protein-coupled receptor-evoked responses of human mast cellsGeetanjali Bansal
Molecular Signal Transduction Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 181:7882-90. 2008..RGS13 overexpression inhibited CXCL12-evoked Ca(2+) mobilization, Akt phosphorylation and chemotaxis. These results suggest that RGS13 restricts certain GPCR-mediated biological responses of human mast cells... - Concurrent inhibition of kit- and FcepsilonRI-mediated signaling: coordinated suppression of mast cell activationBettina M Jensen
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11C206, 10 Center Drive, MSC 1881, Bethesda, MD 20892 1881, USA
J Pharmacol Exp Ther 324:128-38. 2008.... - CD72 negatively regulates KIT-mediated responses in human mast cellsTatsuki R Kataoka
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 184:2468-75. 2010..Furthermore, BU40 and rCD100 also downregulated the growth of the HMC1.2 human mast cell line. Thus, targeting CD72 may provide a novel approach to the suppression of mast cell disease such as mastocytosis... - Kit and FcepsilonRI mediate unique and convergent signals for release of inflammatory mediators from human mast cellsThomas R Hundley
National Institutes of Health, Bethesda, MD 20892 1760, USA
Blood 104:2410-7. 2004..The findings, in total, indicated that a combination of FcepsilonRI and Kit-mediated signals and transcriptional processes were required for optimal physiologic responses of human mast cells to antigen... - Cutting edge: genetic variation influences Fc epsilonRI-induced mast cell activation and allergic responsesYumi Yamashita
Molecular Inflammation Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 179:740-3. 2007..The findings demonstrate a genetic influence on the extent of a mast cell's response and identify Fyn kinase as a contributory determinant... - Activation and function of the mTORC1 pathway in mast cellsMi Sun Kim
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA
J Immunol 180:4586-95. 2008..Specifically, the mTORC1 pathway may play a critical role in normal and dysregulated control of mast cell homeostasis... - Prostaglandin E2 activates and utilizes mTORC2 as a central signaling locus for the regulation of mast cell chemotaxis and mediator releaseHye Sun Kuehn
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 286:391-402. 2011..These findings are consistent with the conclusion that activation of mTORC2, downstream of PI3K, represents a critical signaling locus for chemotaxis and chemokine release from PGE(2)-activated mast cells... - IL-33 induces a hyporesponsive phenotype in human and mouse mast cellsMi Yeon Jung
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 190:531-8. 2013..The ability to downregulate MC activation in this manner may provide alternative approaches for treatment of MC-driven disease... - Glycogen synthase kinase-3β is a prosurvival signal for the maintenance of human mast cell homeostasisMadeleine Radinger
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1881, USA
J Immunol 187:5587-95. 2011..Our data suggest that targeting of GSK3β with small m.w. inhibitors such as CHIR 99021 may thus provide a mechanism for limiting mast cell survival and subsequently decreasing the intensity of the allergic inflammatory response... - The phospholipase C gamma 1-dependent pathway of Fc epsilon RI-mediated mast cell activation is regulated independently of phosphatidylinositol 3-kinaseChristine Tkaczyk
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 278:48474-84. 2003..However, PI 3-kinase may contribute to the later phase of Fc epsilon RI-mediated degranulation in human mast cells... - Mechanisms of mast cell signaling in anaphylaxisDean D Metcalfe
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
J Allergy Clin Immunol 124:639-46; quiz 647-8. 2009..These studies have revealed that signaling pathways exist to both upregulate and downregulate mast cell responses. In this review we will thus describe the key molecular players in these pathways in the context of anaphylaxis... - Cutting Edge: Lentiviral short hairpin RNA silencing of PTEN in human mast cells reveals constitutive signals that promote cytokine secretion and cell survivalYasuko Furumoto
Molecular Inflammation Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 176:5167-71. 2006..The findings demonstrate that PTEN functions as a key regulator of mast cell homeostasis and FcepsilonRI-responsiveness... - Distinct PGE2-responder and non-responder phenotypes in human mast cell populations: "all or nothing" enhancement of antigen-dependent mediator releaseHye Sun Kuehn
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1881, USA
Immunol Lett 141:45-54. 2011.... - Glycogen synthase kinase 3beta activation is a prerequisite signal for cytokine production and chemotaxis in human mast cellsMadeleine Radinger
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1881, USA
J Immunol 184:564-72. 2010..These studies provide evidence for a novel prerequisite priming mechanism for KIT-dependent responses regulated by GSK3beta in HuMCs... - Comparison of Fc epsilon RI- and Fc gamma RI-mediated degranulation and TNF-alpha synthesis in human mast cells: selective utilization of phosphatidylinositol-3-kinase for Fc gamma RI-induced degranulationYoshimichi Okayama
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11C206, 10 Center Drive MSC 1881, Bethesda, MD 20892-1881, USA
Eur J Immunol 33:1450-9. 2003..The one exception was that, although phosphatidylinositol-3-kinase was activated after both Fc epsilon RI and Fc gamma RI aggregation, only the Fc gamma RI appeared to require this molecule for degranulation... - Canonical transient receptor potential 5 channel in conjunction with Orai1 and STIM1 allows Sr2+ entry, optimal influx of Ca2+, and degranulation in a rat mast cell lineHong Tao Ma
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 180:2233-9. 2008..These and other observations suggest that the Sr(2+)-permeable TRPC5 associates with STIM1 and Orai1 in a stoichiometric manner to enhance entry of Ca(2+) to generate a signal for degranulation... - Amplification mechanisms for the enhancement of antigen-mediated mast cell activationAlasdair M Gilfillan
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive MSC 1881, Bethesda, MD, 20892 1881, USA
Immunol Res 43:15-24. 2009..In this review, we describe our research exploring the mechanisms regulating these synergistic interactions and, furthermore, discuss the relevance of our observations in the context of clinical considerations... - The multiple roles of phosphoinositide 3-kinase in mast cell biologyMi Sun Kim
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Trends Immunol 29:493-501. 2008..Furthermore, we describe how different mast cell receptors use alternative isoforms of PI3K for these functions and discuss potential downstream targets of these isoforms... - TLR-mediated signaling pathways circumvent the requirement for DAP12 in mast cells for the induction of inflammatory mediator releaseDaniel Smrz
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1881, USA
Eur J Immunol 40:3557-69. 2010.... - Roles of adaptor molecules in mast cell activationShoko Iwaki
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1881, USA
Chem Immunol Allergy 87:43-58. 2005..In this chapter, we discuss the structure and properties of these molecules and how these proteins regulate the cellular processes associated with receptor-mediated mast cell activation... - Identification of Fyn-binding proteins in MC/9 mast cells using mass spectrometryDong-Ho Nahm
National Institutes of Health, National Institute of Allergy and Infectious Diseases, Laboratory of Allergic Diseases, Building 10, Room 11C206, 10 Center Drive, Bethesda, MD 20892-1881, USA
Biochem Biophys Res Commun 310:202-8. 2003.... - Endosomal trafficking of the ligated FcvarepsilonRI receptorGul nar V Fattakhova
Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, United States
Mol Immunol 46:793-802. 2009.... - 5-hydroxytryptamine induces mast cell adhesion and migrationNataliya M Kushnir-Sukhov
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
J Immunol 177:6422-32. 2006..Furthermore, both mouse and human MC respond to 5-HT through the 5-HT(1A) receptor. Our data are consistent with the conclusion that 5-HT promotes inflammation by increasing MC at the site of tissue injury... - A novel KIT-deficient mouse mast cell model for the examination of human KIT-mediated activation responsesDaniel Smrz
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, MSC 1881, Bethesda, MD 20892 1881, USA
J Immunol Methods 390:52-62. 2013..This cell line thus presents a novel system to delineate how MC function is modulated by native and mutated KIT and for the identification of novel inhibitors of these processes... - G protein-coupled receptors and the modification of FcepsilonRI-mediated mast cell activationHye Sun Kuehn
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive MSC 1881, Bethesda, MD 20892 1881, USA
Immunol Lett 113:59-69. 2007..Furthermore, we discuss the potential mechanisms whereby the signalling responses utilized by the FcepsilonRI for mast cell activation are influenced by those initiated by GPCRs to produce these diverse responses... - Ntal/Lab/Lat2Shoko Iwaki
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11C206, 10 Center Drive, MSC 1881, Bethesda, MD 20892 1881, USA
Int J Biochem Cell Biol 39:868-73. 2007.... - Fcgamma receptors on mast cells: activatory and inhibitory regulation of mediator releaseChristine Tkaczyk
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1881, USA
Int Arch Allergy Immunol 133:305-15. 2004..The exploitation of FcgammaRs for a potential therapy for the treatment of allergic disorders is discussed in this context... - Measuring mast cell mediator releaseHye Sun Kuehn
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
Curr Protoc Immunol . 2010.... - Generation, isolation, and maintenance of human mast cells and mast cell lines derived from peripheral blood or cord bloodMadeleine Radinger
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
Curr Protoc Immunol . 2010..In this unit, techniques for the development and culture of human mast cells from their progenitors and the culture of human mast cell lines are described. The relative merits and drawbacks of each model are also described... - Examination of the role of TRPM8 in human mast cell activation and its relevance to the etiology of cold-induced urticariaNevenka Medic
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1881, USA
Cell Calcium 50:473-80. 2011..From these data, we conclude that TRPM8 is unlikely to directly regulate mast cell activation in cold urticaria. Thus, alternative mechanisms likely exist for the pathogenesis of this disease... - Targeting kit activation: a potential therapeutic approach in the treatment of allergic inflammationBettina M Jensen
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11C206, 10 Center Drive MSC 1881, Bethesda, MD 20892 1881, USA
Inflamm Allergy Drug Targets 6:57-62. 2007..In this review, we provide an overview of the role of SCF and Kit in mast cell activation and discuss potential drug candidates for targeting this response... - Generation, isolation, and maintenance of rodent mast cells and mast cell linesBettina M Jensen
National Institutes of Health, Bethesda, Maryland, USA
Curr Protoc Immunol . 2006..In this unit, we describe the protocols used for the isolation and/or culture of these cells and discuss the relative merits of their use... - The high-affinity immunoglobulin-E receptor (FcepsilonRI) is endocytosed by an AP-2/clathrin-independent, dynamin-dependent mechanismMadhan Masilamani
Receptor Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
Traffic 7:673-85. 2006..We conclude that internalization of cross-linked FcRI does not require the AP-2/clathrin complex but is dynamin-dependent and may be lipid raft mediated... - IgE-dependent activation of sphingosine kinases 1 and 2 and secretion of sphingosine 1-phosphate requires Fyn kinase and contributes to mast cell responsesAna Olivera
Molecular Inflammation Section, Molecular Immunology and Inflammation Branch, NIAMS, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 281:2515-25. 2006..Taken together with our previous study, which demonstrated delayed SphK activation in Lyn-deficient BMMC, we propose a cooperative role between Fyn and Lyn kinases in the activation of SphKs, which contributes to mast cell responses... - Activation of human mast cells through the high affinity IgG receptorChristine Tkaczyk
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11C205, 10 Center Drive MSC 1881, Bethesda, MD 2089 1881, USA
Mol Immunol 38:1289-93. 2002..These observations provide evidence that human mast cells may also be recruited into inflammation through IgG-dependent mechanisms... - Determination of protein phosphorylation in Fc epsilon RI-activated human mast cells by immunoblot analysis requires protein extraction under denaturing conditionsChristine Tkaczyk
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11C213, 10 Center Drive MSC 1881, Bethesda, MD 20892-1881, USA
J Immunol Methods 268:239-43. 2002..The data presented in this report would be applicable to other cell types where high concentrations of proteases are present... - IgE-FcepsilonRI interactions determine HIV coreceptor usage and susceptibility to infection during ontogeny of mast cellsJ Bruce Sundstrom
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
J Immunol 182:6401-9. 2009.... - Defective eosinophil hematopoiesis ex vivo in inbred Rocky Mountain White (IRW) miceKimberly D Dyer
Eosinophil Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy andInfectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
J Leukoc Biol 90:1101-9. 2011..These results suggest that IRW mice have diminished capacity to generate eosinophils in culture and in vivo, likely as a result of diminished signaling via IL-5Rα... - Molecular regulation of mast cell activationJuan Rivera
Molecular Inflammation Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892 1820, USA
J Allergy Clin Immunol 117:1214-25; quiz 1226. 2006..The unifying theme is that the regulatory steps mentioned herein are required for promoting effective responses while protecting against unwanted inflammatory responses... - Adaptive and innate immune reactions regulating mast cell activation: from receptor-mediated signaling to responsesChristine Tkaczyk
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11C206, 10 Center Drive, MSC 1881, Bethesda, MD 20892, USA
Immunol Allergy Clin North Am 26:427-50. 2006..The exact interconnections between the signaling pathways initiated by the surface receptors described in this article remain to be completely worked out; thus, this remains a topic for future investigation... - The tyrosine kinase network regulating mast cell activationAlasdair M Gilfillan
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1930, USA
Immunol Rev 228:149-69. 2009..In this review, we discuss the regulation and role of specific members of this tyrosine kinase network in KIT and Fc epsilon RI-mediated mast cell activation... - Nitric oxide inhibits IgE-dependent cytokine production and Fos and Jun activation in mast cellsBeverley J Davis
Department of, Pharmacology, University of Liverpool, United Kingdom
J Immunol 173:6914-20. 2004..These results show that NO is capable of inhibiting FcepsilonRI-dependent mast cell cytokine production at the level of gene regulation, and suggest too that NO may contribute to resolution of allergic inflammation... - Essential role for the p110delta phosphoinositide 3-kinase in the allergic responseKhaled Ali
Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, UK
Nature 431:1007-11. 2004..Inactivation of p110delta protects mice against anaphylactic allergic responses. These results identify p110delta as a new target for therapeutic intervention in allergy and mast-cell-related pathologies...