Activation of Mast Cells in Disease States: Pharmacological Modification

疾病状态下肥大细胞的激活:药理学修饰

基本信息

项目摘要

Mast cells play a pivotal role in the pathogenesis of asthma and other allergic diseases. These reactions are generally initiated by antigen-dependent aggregation of the high affinity IgE receptor (Fc-epsilon-RI) expressed on the cell surface and subsequent release of pro-inflammatory mediators (e.g. histamine, eicosanoids, proteases and cytokines). We wish to identify disease states and clinical populations where hyper-responsive and low-responsive mast cells exist and to identify specific signaling defects responsible for these phenotypes. In addition to the FcepsilonRI, there is an increasing appreciation that other receptors (and other stimuli) may profoundly influence antigen-mediated degranulation. Activating polymorphisms/mutations in, and alternatively spliced forms of receptors and/or signaling proteins may further modulate these responses. Such polymorphisms associated with disease states, for example mastocytosis, may be manifested by exacerbated mast cell-dependent physiology. We wish therefore to also explore the role of other mast cell receptors in disease states and how polymorphisms or alternatively spliced variants of receptors or signaling proteins may produce a hyperactive phenotype. Finally, we wish to explore potential approaches for inhibiting these responses.
肥大细胞在哮喘和其他过敏性疾病的发病机制中发挥着关键作用。这些反应通常是由细胞表面表达的高亲和力 IgE 受体 (Fc-epsilon-RI) 的抗原依赖性聚集以及随后促炎介质(例如组胺、类二十烷酸、蛋白酶和细胞因子)的释放引发的。我们希望确定存在高反应性和低反应性肥大细胞的疾病状态和临床人群,并确定导致这些表型的特定信号传导缺陷。除了 FcepsilonRI 之外,人们越来越认识到其他受体(和其他刺激物)可能会深刻影响抗原介导的脱颗粒。 激活受体和/或信号蛋白的多态性/突变和选择性剪接形式可以进一步调节这些反应。与疾病状态例如肥大细胞增多症相关的此类多态性可以通过加剧的肥大细胞依赖性生理学来体现。因此,我们还希望探索其他肥大细胞受体在疾病状态中的作用,以及受体或信号蛋白的多态性或选择性剪接变体如何产生过度活跃的表型。最后,我们希望探索抑制这些反应的潜在方法。

项目成果

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Dean D Metcalfe其他文献

Plasma IL-6 correlates with disease category and with hematological parameters in patients with mastocytosis
  • DOI:
    10.1016/s0091-6749(02)81601-3
  • 发表时间:
    2002-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Knut Brockow;Cem Akin;Mary M Huber;Dean D Metcalfe
  • 通讯作者:
    Dean D Metcalfe
Comparison of FceRI and FcγRI-dependent signaling pathways in human mast cells
  • DOI:
    10.1016/s0091-6749(02)82259-x
  • 发表时间:
    2002-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Christine Tkaczyk;Yoshimishi Okayama;Dean D Metcalfe;Alasdair M Gilfillan
  • 通讯作者:
    Alasdair M Gilfillan
Serum tryptase levels combined with flow cytometric analysis of bone marrow aspirate mast cells differentiate systemic mastocytosis from idiopathic syndromes
  • DOI:
    10.1016/s0091-6749(02)81675-x
  • 发表时间:
    2002-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Cem Akin;Arnold S Kirshenbaum;Dean D Metcalfe
  • 通讯作者:
    Dean D Metcalfe
Direct determination of allergen specific T cell cytokine responses during immunotherapy
  • DOI:
    10.1016/s0091-6749(02)82225-4
  • 发表时间:
    2002-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    L Brigida Cayosa Hunter;Varatda Plainetr;Barbara Foster;Mary M Huber;Dean D Metcalfe;Calman Prussin
  • 通讯作者:
    Calman Prussin

Dean D Metcalfe的其他文献

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{{ truncateString('Dean D Metcalfe', 18)}}的其他基金

REGULATION OF CYTOKINE GENE EXPRESSION IN MAST CELLS
肥大细胞中细胞因子基因表达的调节
  • 批准号:
    6098983
  • 财政年份:
  • 资助金额:
    $ 31.67万
  • 项目类别:
Developmental Immunotherapeutics for Allergic Diseases and Asthma
过敏性疾病和哮喘的发育免疫治疗
  • 批准号:
    6099081
  • 财政年份:
  • 资助金额:
    $ 31.67万
  • 项目类别:
Fc Receptors in Mast Cell Signaling and Function
肥大细胞信号传导和功能中的 Fc 受体
  • 批准号:
    6431716
  • 财政年份:
  • 资助金额:
    $ 31.67万
  • 项目类别:
The Pathogenesis, Diagnosis, And Treatment Of Systemic Mast Cell Disorders
系统性肥大细胞疾病的发病机制、诊断和治疗
  • 批准号:
    7964210
  • 财政年份:
  • 资助金额:
    $ 31.67万
  • 项目类别:
Clinical and Immunological Evaluation of Children with Allergic Disease
儿童过敏性疾病的临床和免疫学评估
  • 批准号:
    7964522
  • 财政年份:
  • 资助金额:
    $ 31.67万
  • 项目类别:
Pathogenesis of Physical Urticaria Syndromes
物理性荨麻疹综合征的发病机制
  • 批准号:
    8946474
  • 财政年份:
  • 资助金额:
    $ 31.67万
  • 项目类别:
Pediatric Inflammatory Diseases of the Respiratory Tract: Asthma
小儿呼吸道炎症疾病:哮喘
  • 批准号:
    7732632
  • 财政年份:
  • 资助金额:
    $ 31.67万
  • 项目类别:
Molecular Biology Of Mast Cell Growth And Differentiation
肥大细胞生长和分化的分子生物学
  • 批准号:
    7732464
  • 财政年份:
  • 资助金额:
    $ 31.67万
  • 项目类别:
The Pathogenesis, Diagnosis, And Treatment Of Systemic Mast Cell Disorders
系统性肥大细胞疾病的发病机制、诊断和治疗
  • 批准号:
    10014014
  • 财政年份:
  • 资助金额:
    $ 31.67万
  • 项目类别:
Pathogenesis and Treatment of Anaphylaxis
过敏反应的发病机制和治疗
  • 批准号:
    10014172
  • 财政年份:
  • 资助金额:
    $ 31.67万
  • 项目类别:

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