Dean D Metcalfe

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. ncbi Mast cells and mastocytosis
    Dean D Metcalfe
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1881, USA
    Blood 112:946-56. 2008
  2. ncbi Mechanisms of mast cell signaling in anaphylaxis
    Dean 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
  3. ncbi Regulation of normal and neoplastic human mast cell development in mastocytosis
    Dean D Metcalfe
    NIH NIAID LAD, Building 10, Room 11C205, 10 Center Drive, MSC 1881, Bethesda, MD 20892 1881, USA
    Trans Am Clin Climatol Assoc 116:185-203; discussion 203-4. 2005
  4. ncbi Genetically modified crops and allergenicity
    Dean D Metcalfe
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892-1881, USA
    Nat Immunol 6:857-60. 2005
  5. ncbi The phosphoinositide 3-kinase-dependent activation of Btk is required for optimal eicosanoid production and generation of reactive oxygen species in antigen-stimulated mast cells
    Hye 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
  6. ncbi NTAL phosphorylation is a pivotal link between the signaling cascades leading to human mast cell degranulation following Kit activation and Fc epsilon RI aggregation
    Christine 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
  7. ncbi Kit- and Fc epsilonRI-induced differential phosphorylation of the transmembrane adaptor molecule NTAL/LAB/LAT2 allows flexibility in its scaffolding function in mast cells
    Shoko 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
  8. ncbi CD72 negatively regulates KIT-mediated responses in human mast cells
    Tatsuki 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
  9. ncbi mTORC1 and mTORC2 differentially regulate homeostasis of neoplastic and non-neoplastic human mast cells
    Daniel 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
  10. ncbi Btk plays a crucial role in the amplification of Fc epsilonRI-mediated mast cell activation by kit
    Shoko Iwaki
    Laboratory of Allergic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892 1881, USA
    J Biol Chem 280:40261-70. 2005

Detail Information

Publications94

  1. ncbi Mast cells and mastocytosis
    Dean D Metcalfe
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1881, USA
    Blood 112:946-56. 2008
    ....
  2. ncbi Mechanisms of mast cell signaling in anaphylaxis
    Dean 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...
  3. ncbi Regulation of normal and neoplastic human mast cell development in mastocytosis
    Dean D Metcalfe
    NIH NIAID LAD, Building 10, Room 11C205, 10 Center Drive, MSC 1881, Bethesda, MD 20892 1881, USA
    Trans Am Clin Climatol Assoc 116:185-203; discussion 203-4. 2005
    ..Non-myeloablative bone marrow transplantation is performed in select patients to take advantage of the immunotherapeutic effects of the graft...
  4. ncbi Genetically modified crops and allergenicity
    Dean D Metcalfe
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892-1881, USA
    Nat Immunol 6:857-60. 2005
  5. ncbi The phosphoinositide 3-kinase-dependent activation of Btk is required for optimal eicosanoid production and generation of reactive oxygen species in antigen-stimulated mast cells
    Hye 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...
  6. ncbi NTAL phosphorylation is a pivotal link between the signaling cascades leading to human mast cell degranulation following Kit activation and Fc epsilon RI aggregation
    Christine 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...
  7. ncbi Kit- and Fc epsilonRI-induced differential phosphorylation of the transmembrane adaptor molecule NTAL/LAB/LAT2 allows flexibility in its scaffolding function in mast cells
    Shoko 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...
  8. ncbi CD72 negatively regulates KIT-mediated responses in human mast cells
    Tatsuki 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...
  9. ncbi mTORC1 and mTORC2 differentially regulate homeostasis of neoplastic and non-neoplastic human mast cells
    Daniel 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
    ....
  10. ncbi Btk plays a crucial role in the amplification of Fc epsilonRI-mediated mast cell activation by kit
    Shoko 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...
  11. ncbi Synergistic activation of phospholipases Cgamma and Cbeta: a novel mechanism for PI3K-independent enhancement of FcepsilonRI-induced mast cell mediator release
    Hye 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...
  12. ncbi Stem cell factor programs the mast cell activation phenotype
    Tomonobu 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
    ....
  13. ncbi Concurrent inhibition of kit- and FcepsilonRI-mediated signaling: coordinated suppression of mast cell activation
    Bettina 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
    ....
  14. ncbi Btk-dependent Rac activation and actin rearrangement following FcepsilonRI aggregation promotes enhanced chemotactic responses of mast cells
    Hye 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...
  15. ncbi Kit and FcepsilonRI mediate unique and convergent signals for release of inflammatory mediators from human mast cells
    Thomas 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...
  16. ncbi Activation and function of the mTORC1 pathway in mast cells
    Mi 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...
  17. ncbi Thrombopoietin alone or in the presence of stem cell factor supports the growth of KIT(CD117)low/ MPL(CD110)+ human mast cells from hematopoietic progenitor cells
    Arnold S Kirshenbaum
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1881, USA
    Exp Hematol 33:413-21. 2005
    ..We explored the ability of TPO alone or in the presence of stem cell factor (SCF) to support human mast cells (HuMCs)...
  18. ncbi IgE, mast cells, basophils, and eosinophils
    Kelly D Stone
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1881, USA
    J Allergy Clin Immunol 125:S73-80. 2010
    ..Mast cells, basophils, and eosinophils are central effector cells in allergic inflammation, as well as in innate and adaptive immunity. This review highlights what is known about these components and their roles in disease pathogenesis...
  19. ncbi IL-33 induces a hyporesponsive phenotype in human and mouse mast cells
    Mi 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...
  20. ncbi Effect of lipopolysaccharide (LPS) and peptidoglycan (PGN) on human mast cell numbers, cytokine production, and protease composition
    Arnold S Kirshenbaum
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    BMC Immunol 9:45. 2008
    ..It is unknown, however, whether long- or short-term exposure to bacteria-derived toll-like receptor (TLR) ligands, such as lipopolysaccharide (LPS) or peptidoglycan (PGN), influences HuMC biology...
  21. ncbi Demonstration that mast cells, T cells, and B cells bearing the activating kit mutation D816V occur in clusters within the marrow of patients with mastocytosis
    Marcia L Taylor
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Room 11C 205, MSC1881, Bethesda, MD 20892 1881, USA
    J Mol Diagn 6:335-42. 2004
    ..Further, the B cell population is oligoclonal, suggesting that clonal proliferation is unlikely to be the basis of clustering...
  22. ncbi FcepsilonRI- and Fcgamma receptor-mediated production of reactive oxygen species by mast cells is lipoxygenase- and cyclooxygenase-dependent and NADPH oxidase-independent
    Emily J Swindle
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1881, USA
    J Immunol 179:7059-71. 2007
    ....
  23. ncbi Glycogen synthase kinase-3β is a prosurvival signal for the maintenance of human mast cell homeostasis
    Madeleine 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...
  24. ncbi The phospholipase C gamma 1-dependent pathway of Fc epsilon RI-mediated mast cell activation is regulated independently of phosphatidylinositol 3-kinase
    Christine 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...
  25. ncbi KIT D816V-associated systemic mastocytosis with eosinophilia and FIP1L1/PDGFRA-associated chronic eosinophilic leukemia are distinct entities
    Irina Maric
    Department of Laboratory Medicine, Clinical Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
    J Allergy Clin Immunol 120:680-7. 2007
    ..It is of paramount importance, however, to distinguish between these 2 groups of patients because of differences in clinical sequelae, prognoses, and selection of treatment...
  26. ncbi IL-6 levels predict disease variant and extent of organ involvement in patients with mastocytosis
    Knut Brockow
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892 1881, USA
    Clin Immunol 115:216-23. 2005
    ..There was an inverse correlation to hemoglobin. sIL-6R levels were not elevated. These observations demonstrate that IL-6 is a useful surrogate marker of severity of hematologic disease and suggest that IL-6 contributes to pathology...
  27. ncbi High-resolution tracking of cell division demonstrates differential effects of TH1 and TH2 cytokines on SCF-dependent human mast cell production in vitro: correlation with apoptosis and Kit expression
    Marianna Kulka
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1881, USA
    Blood 105:592-9. 2005
    ..Thus, exposure of human mast cells to IL-4, IL-5, and IFN-gamma during growth and differentiation generally down-regulated mast cell number and function, whereas IL-4 increased mature mast cell division and degranulation...
  28. ncbi Prostaglandin E2 activates and utilizes mTORC2 as a central signaling locus for the regulation of mast cell chemotaxis and mediator release
    Hye 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...
  29. ncbi Effects of gamma radiation on FcepsilonRI and TLR-mediated mast cell activation
    Benjamin P Soule
    Radiation Biology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
    J Immunol 179:3276-86. 2007
    ..Mast cells are thus resistant to the cytotoxic effects and alterations in function after irradiation and, despite a transient inhibition, ultimately respond to innate and acquired immune activation signals...
  30. ncbi Clonal analysis of NRAS activating mutations in KIT-D816V systemic mastocytosis
    Todd M Wilson
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892 1881, USA
    Haematologica 96:459-63. 2011
    ..Unlike other mature lineages, mast cell survival is dependent on KIT and the presence of these two activating mutations may have a greater impact on the expansion of this cell compartment and in resultant disease severity...
  31. ncbi Elevated serum tryptase levels identify a subset of patients with a myeloproliferative variant of idiopathic hypereosinophilic syndrome associated with tissue fibrosis, poor prognosis, and imatinib responsiveness
    Amy D Klion
    Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 101:4660-6. 2003
    ..In summary, elevated serum tryptase appears to be a sensitive marker of a myeloproliferative variant of HES that is characterized by tissue fibrosis, poor prognosis, and imatinib responsiveness...
  32. ncbi Effects of tyrosine kinase inhibitor STI571 on human mast cells bearing wild-type or mutated c-kit
    Cem Akin
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1881, USA
    Exp Hematol 31:686-92. 2003
    ..Because activating mutations of c-kit affecting codon 816 are associated with human mast cell neoplasms, we determined whether STI571 exerted a similar cytotoxic effect on neoplastic and normal human mast cells...
  33. ncbi Bone marrow stromal cells use TGF-beta to suppress allergic responses in a mouse model of ragweed-induced asthma
    Krisztian Nemeth
    National Institute of Dental and Craniofacial Research, Craniofacial and Skeletal Diseases Branch, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 107:5652-7. 2010
    ....
  34. ncbi Distinct PGE2-responder and non-responder phenotypes in human mast cell populations: "all or nothing" enhancement of antigen-dependent mediator release
    Hye 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
    ....
  35. ncbi Molecular remission and reversal of myelofibrosis in response to imatinib mesylate treatment in patients with the myeloproliferative variant of hypereosinophilic syndrome
    Amy D Klion
    Bldg 4, Rm 126, National Institutes of Health, Bethesda, MD 20892
    Blood 103:473-8. 2004
    ..The lack of reversal of cardiac abnormalities and persistence of the F/P mutation in some patients suggests that early intervention with higher doses of imatinib mesylate may be desirable in the treatment of patients with MHES...
  36. ncbi 5-hydroxytryptamine induces mast cell adhesion and migration
    Nataliya 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...
  37. ncbi Silica-directed mast cell activation is enhanced by scavenger receptors
    Jared M Brown
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1881, USA
    Am J Respir Cell Mol Biol 36:43-52. 2007
    ..These findings demonstrate that silica directs mast cell production of inflammatory mediators, in part through SRs, providing insight into critical events in the pathogenesis and potential therapeutic targets in silicosis...
  38. ncbi Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with "idiopathic" anaphylaxis
    Cem Akin
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health NIH, Bethesda, MD, USA
    Blood 110:2331-3. 2007
    ..This intramural clinical trial was conducted in 2003 and 2004 and was registered at (http://clinicalcenter.nih.gov) with a study number 03-I-0010. Since the study is now closed, it is no longer available online...
  39. ncbi Human dendritic cell 1 and dendritic cell 2 subsets express FcepsilonRI: correlation with serum IgE and allergic asthma
    Barbara Foster
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1881, USA
    J Allergy Clin Immunol 112:1132-8. 2003
    ..These data support the concept that novel therapeutic approaches directly targeted at FcepsilonRI expression would affect both the sensitization and the effector phases of the allergen-specific immune response...
  40. ncbi TLR-mediated signaling pathways circumvent the requirement for DAP12 in mast cells for the induction of inflammatory mediator release
    Daniel 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
    ....
  41. ncbi A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib
    Cem Akin
    Laboratory of Allergic Diseases, National Instititute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 103:3222-5. 2004
    ....
  42. ncbi Anti-IgE treatment of eosinophil-associated gastrointestinal disorders
    Shabnam Foroughi
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
    J Allergy Clin Immunol 120:594-601. 2007
    ..Eosinophil-associated gastrointestinal disorders (EGIDs) are commonly associated with atopy and are being recognized with increasing frequency. Current therapy for EGIDs is inadequate...
  43. ncbi Understanding the mechanisms of anaphylaxis
    Richard D Peavy
    Laboratory of Allergic Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892 1881, USA
    Curr Opin Allergy Clin Immunol 8:310-5. 2008
    ..The present review considers recent reports that identify the roles of key intermediate signaling components and mediators during and after mast cell activation and degranulation leading to anaphylaxis...
  44. ncbi Amplification mechanisms for the enhancement of antigen-mediated mast cell activation
    Alasdair 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...
  45. ncbi Glycogen synthase kinase 3beta activation is a prerequisite signal for cytokine production and chemotaxis in human mast cells
    Madeleine 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...
  46. ncbi IL-5 receptor α levels in patients with marked eosinophilia or mastocytosis
    Todd M Wilson
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
    J Allergy Clin Immunol 128:1086-92.e1-3. 2011
    ..Although IL-5, IL-3, and GM-CSF can modulate the expression of IL-5 receptor α (IL-5Rα) on eosinophils in vitro, little is known about soluble and surface IL-5Rα levels in vivo...
  47. ncbi Endosomal trafficking of the ligated FcvarepsilonRI receptor
    Gul 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
    ....
  48. ncbi 5. IgE, mast cells, basophils, and eosinophils
    Calman Prussin
    Laboratory of Allergic Diseases, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Building 10, Rm. 11C-205, 10 Center Drive, Bethesda, MD 20892, USA
    J Allergy Clin Immunol 117:S450-6. 2006
    ..Aggregation of receptor-bound IgE molecules on re-exposure to specific allergen results in the production of mediators that produce the allergic response. Principal among the cells drawn to sites of mediator release is the eosinophil...
  49. ncbi 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 degranulation
    Yoshimichi 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...
  50. ncbi Activation of human mast cells by aggregated IgG through FcgammaRI: additive effects of C3a
    Michael R Woolhiser
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Clin Immunol 110:172-80. 2004
    ..3). Simultaneous activation of huMC via aggregated IgG and C3a led to additive degranulation. These data support a mechanism by which mast cells may contribute to the inflammatory component in fibrosis, vasculitis, and arthritis...
  51. ncbi Roles of adaptor molecules in mast cell activation
    Shoko 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...
  52. ncbi Analysis of the lineage relationship between mast cells and basophils using the c-kit D816V mutation as a biologic signature
    Can N Kocabas
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases/NIH, Bethesda, MD 20892, USA
    J Allergy Clin Immunol 115:1155-61. 2005
    ..These results argue against the presence of a bilineage-restricted committed progenitor for mast cells and basophils...
  53. ncbi Assessment of the extent of cutaneous involvement in children and adults with mastocytosis: relationship to symptomatology, tryptase levels, and bone marrow pathology
    Knut Brockow
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1881, USA
    J Am Acad Dermatol 48:508-16. 2003
    ..CONCLUSION: An examination of the extent and density of cutaneous lesions in adults helps identify those with more extensive extracutaneous disease and, thus, requiring a more thorough evaluation...
  54. ncbi Identification of Fyn-binding proteins in MC/9 mast cells using mass spectrometry
    Dong-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
    ....
  55. ncbi Tryptase haplotype in mastocytosis: relationship to disease variant and diagnostic utility of total tryptase levels
    Cem Akin
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA
    Clin Immunol 123:268-71. 2007
    ..Total and mature tryptase levels positively correlated with disease severity, as well as prothrombin time and partial thromboplastin time, and negatively correlated with the hemoglobin concentration...
  56. ncbi A novel KIT-deficient mouse mast cell model for the examination of human KIT-mediated activation responses
    Daniel 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...
  57. ncbi Examination of the role of TRPM8 in human mast cell activation and its relevance to the etiology of cold-induced urticaria
    Nevenka 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...
  58. ncbi Pediatric-onset mastocytosis: a long term clinical follow-up and correlation with bone marrow histopathology
    Ashraf Uzzaman
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
    Pediatr Blood Cancer 53:629-34. 2009
    ..We addressed the long term prognosis of pediatric-onset disease by examining 17 children with mastocytosis which we had reported on in 1989 [1]...
  59. ncbi Targeting kit activation: a potential therapeutic approach in the treatment of allergic inflammation
    Bettina 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...
  60. ncbi Fcgamma receptors on mast cells: activatory and inhibitory regulation of mediator release
    Christine 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...
  61. ncbi Characterization of novel stem cell factor responsive human mast cell lines LAD 1 and 2 established from a patient with mast cell sarcoma/leukemia; activation following aggregation of FcepsilonRI or FcgammaRI
    Arnold S Kirshenbaum
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1881, USA
    Leuk Res 27:677-82. 2003
    ..Both LAD 1 and 2 release beta-hexosaminidase following FcepsilonRI or FcgammaRI aggregation. The availability of these cell lines offers an unparalleled circumstance to examine the biology of human mast cells...
  62. ncbi Gene expression analysis in mastocytosis reveals a highly consistent profile with candidate molecular markers
    Cem Akin
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases (NIAID, Bethesda, MD 20892-1881, USA
    J Allergy Clin Immunol 112:1162-70. 2003
    ....
  63. ncbi Activation of human mast cells through the high affinity IgG receptor
    Christine 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...
  64. ncbi Growth of human mast cells from bone marrow and peripheral blood-derived CD34+ pluripotent progenitor cells
    Arnold S Kirshenbaum
    Laboratory of Allergic Diseases, Mast Cell Biology Section, NIH/NIAID, Bethesda, MD, USA
    Methods Mol Biol 315:105-12. 2006
    ..Weekly hemidepletions and the removal of adherent cells and/or debris enables the investigator to obtain HMC cultures, identified by Wright-Giemsa and acidic toluidine blue stains, by 8-10 wk...
  65. ncbi Characterization of mast-cell tryptase-expressing peripheral blood cells as basophils
    Barbara Foster
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda 20892-1881, USA
    J Allergy Clin Immunol 109:287-93. 2002
    ..These results demonstrate that tryptase represents an additional mediator through which basophils may contribute to allergic inflammation...
  66. ncbi Introduction: what are the issues in addressing the allergenic potential of genetically modified foods?
    Dean D Metcalfe
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
    Environ Health Perspect 111:1110-3. 2003
    ....
  67. ncbi Regression of urticaria pigmentosa in adult patients with systemic mastocytosis: correlation with clinical patterns of disease
    Knut Brockow
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-1881, USA
    Arch Dermatol 138:785-90. 2002
    ..In contrast, regression of UP in patients with indolent SM parallels a decrease in disease intensity, although bone marrow findings of indolent SM remain...
  68. ncbi The role of reactive oxygen species and nitric oxide in mast cell-dependent inflammatory processes
    Emily J Swindle
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 6961, USA
    Immunol Rev 217:186-205. 2007
    ..In addition, we examine the evidence for a functional role for ROS and RNOS in mast cell secretory responses and discuss evidence for a direct relationship between ROS, RNOS, and mast cells in mast cell-dependent inflammatory conditions...
  69. ncbi Pediatric mastocytosis: routine anesthetic management for a complex disease
    Melody C Carter
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Dr MSC 1881, Bldg 10 Room 11C 213, Bethesda, MD 20892, USA
    Anesth Analg 107:422-7. 2008
    ..Mast cells are instrumental in mediating anaphylaxis and patients with mastocytosis are at risk to develop provoked and unprovoked episodes of anaphylaxis...
  70. ncbi An immunohistochemical study of the bone marrow lesions of systemic mastocytosis: expression of stem cell factor by lesional mast cells
    Cem Akin
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1881, USA
    Am J Clin Pathol 118:242-7. 2002
    ....
  71. ncbi IgE(+), Kit(-), I-A/I-E(-) myeloid cells are the initial source of Il-4 after antigen challenge in a mouse model of allergic pulmonary inflammation
    Stefano Luccioli
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA
    J Allergy Clin Immunol 110:117-24. 2002
    ..These data thus suggest that strategies targeting basophils should be considered in the treatment of early lung inflammation...
  72. ncbi Evidence for the involvement of a hematopoietic progenitor cell in systemic mastocytosis from single-cell analysis of mutations in the c-kit gene
    A Selim Yavuz
    Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIAMS, and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases NIAID, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 100:661-5. 2002
    ....
  73. ncbi Impulse oscillometry in the evaluation of diseases of the airways in children
    Hirsh D Komarow
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892 1960, USA
    Ann Allergy Asthma Immunol 106:191-9. 2011
    ..To provide an overview of impulse oscillometry and its application to the evaluation of children with diseases of the airways...
  74. ncbi Mast cell biology: introduction and overview
    Alasdair 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...
  75. ncbi Mastocytosis: current treatment concepts
    Alexandra S Worobec
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1181, USA
    Int Arch Allergy Immunol 127:153-5. 2002
    ..The future will undoubtedly witness an even greater array of therapeutic options, as we continue to learn more about this enigmatic disease...
  76. ncbi Surrogate markers of disease in mastocytosis
    Cem Akin
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1881, USA
    Int Arch Allergy Immunol 127:133-6. 2002
    ..In addition, several novel markers including soluble CD117 and soluble CD25 have been identified in recent studies. The utility and the pitfalls of each of these measurements are discussed...
  77. ncbi Levels of mast-cell growth factors in plasma and in suction skin blister fluid in adults with mastocytosis: correlation with dermal mast-cell numbers and mast-cell tryptase
    Knut Brockow
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1881, USA
    J Allergy Clin Immunol 109:82-8. 2002
    ....
  78. ncbi Rodent and human mast cells produce functionally significant intracellular reactive oxygen species but not nitric oxide
    Emily J Swindle
    Department of Pharmacology, University of Liverpool, Liverpool L69 3GE, United Kingdom
    J Biol Chem 279:48751-9. 2004
    ..We conclude that rodent and human mast cells generate intracellular ROS but not NO and that intracellular ROS but not intracellular NO are functionally linked to mast cell degranulation...
  79. ncbi F(ab)'2-mediated neutralization of C3a and C5a anaphylatoxins: a novel effector function of immunoglobulins
    Milan Basta
    Neuronal Excitability Section, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
    Nat Med 9:431-8. 2003
    ..This binding could interfere with the role of C3a and C5a in inflammation...
  80. ncbi Office-based management of urticaria
    Hirsh D Komarow
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1894, USA
    Am J Med 121:379-84. 2008
    ..In severe cases, corticosteroids, hydroxychloroquine sulfate (Plaquenil; Sanofi-Synthelabo, New York, NY), and immunosuppressive agents, including cyclosporin, are sometimes used by specialists...
  81. ncbi Systemic mastocytosis
    Cem Akin
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Annu Rev Med 55:419-32. 2004
    ..These findings are being used in formulating diagnostic criteria as well as designing novel treatment approaches to the disease...
  82. ncbi Elevated tryptase levels are associated with greater bone density in a cohort of patients with mastocytosis
    Nataliya M Kushnir-Sukhov
    Laboratory of Allergic Diseases, NIAID, NIH, Bethesda, MD 20892 1881, USA
    Int Arch Allergy Immunol 139:265-70. 2006
    ..Mastocytosis is associated with a pathological increase in tissue mast cells. Associated skeletal problems include a decrease in bone density and pathological fractures...
  83. ncbi Adrenomedullin is a cross-talk molecule that regulates tumor and mast cell function during human carcinogenesis
    Enrique Zudaire
    CCBB, CCR, National Cancer Institute, Bldg 10, RM, 12N226, Bethesda, MD 20892, USA
    Am J Pathol 168:280-91. 2006
    ..Our collective data suggest a new role for AM as a cross-talk molecule that integrates tumor and MC communication, underlying a unique promotion mechanism of human cancers...
  84. ncbi IgE-FcepsilonRI interactions determine HIV coreceptor usage and susceptibility to infection during ontogeny of mast cells
    J Bruce Sundstrom
    Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Immunol 182:6401-9. 2009
    ....
  85. ncbi Mastocytosis
    Dean D Metcalfe
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Novartis Found Symp 271:232-42; discussion 242-9. 2005
    ..The value of bone marrow transplantation remains under investigation...
  86. ncbi Mastocytosis and disorders of mast cell proliferation
    Joanne K Simpson
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Clin Rev Allergy Immunol 22:175-88. 2002
  87. ncbi Activity of imatinib in systemic mastocytosis with chronic basophilic leukemia and a PRKG2-PDGFRB fusion
    Idoya Lahortiga
    Human Genome Laboratory, Department of Molecular and Developmental Genetics, VIB, Leuven, Belgium
    Haematologica 93:49-56. 2008
    ..We report an unusual case of a patient presenting with peripheral basophilia and systemic mastocytosis in whom cytogenetic analysis revealed a t(4;5)(q21.1;q31.3)...
  88. ncbi Nitric oxide inhibits IgE-dependent cytokine production and Fos and Jun activation in mast cells
    Beverley 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...
  89. ncbi Functional and phenotypic studies of two variants of a human mast cell line with a distinct set of mutations in the c-kit proto-oncogene
    Magnus Sundstrom
    Laboratory of Tumor Biology, Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden
    Immunology 108:89-97. 2003
    ....
  90. ncbi Mast cell proliferative disorders: current view on variants recognized by the World Health Organization
    Peter Valent
    Department of Internal Medicine 1, Division of Hematology and Hemostaseology, University of Vienna, Wahringer Gurtel 18 20, Vienna, Austria
    Hematol Oncol Clin North Am 17:1227-41. 2003
    ..In patients with SM-AHNMD, the SM should be treated as if no AHNMD is present, and the AHNMD should be treated as if no SM had been diagnosed...
  91. ncbi The c-KIT mutation causing human mastocytosis is resistant to STI571 and other KIT kinase inhibitors; kinases with enzymatic site mutations show different inhibitor sensitivity profiles than wild-type kinases and those with regulatory-type mutations
    Yongsheng Ma
    Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Blood 99:1741-4. 2002
    ..Furthermore, these results help establish a general paradigm whereby classification of mutations affecting oncogenic enzymes as RT or EST may be useful in predicting tumor sensitivity or resistance to inhibitory drugs...
  92. ncbi Risk assessment in anaphylaxis: current and future approaches
    F Estelle R Simons
    Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada, and Department of Respiratory Medicine, Brighton General Hospital, Belfast, UK
    J Allergy Clin Immunol 120:S2-24. 2007
    ....
  93. ncbi The biology of Kit in disease and the application of pharmacogenetics
    Cem Akin
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA
    J Allergy Clin Immunol 114:13-9; quiz 20. 2004
    ..This review will discuss the pathobiology of Kit in human disease, with a particular emphasis on implications for potential targeted treatment strategies in mast cell disease...
  94. ncbi Mast cells, which interact with Escherichia coli, up-regulate genes associated with innate immunity and become less responsive to Fc(epsilon)RI-mediated activation
    Marianna Kulka
    Allergy-Immunology Division, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
    J Leukoc Biol 79:339-50. 2006
    ..These data are consistent with the concept that bacterial exposure directs mast cell responses toward innate immunity and away from IgE-mediated effects...