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Human Eosinophils: Mechanisms of Functioning

人类嗜酸性粒细胞：功能机制

基本信息

批准号：
7878373
负责人：
PETER F WELLER
金额：
$ 1.97万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-15 至 2010-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7878373
关键词：
ADP-Ribosylation Factors Abbreviations Accounting Acute Allergic Antibodies Arachidonate 5-Lipoxygenase Arylsulfatase B Asthma Biological Assay Brefeldin A Cells Chronic Disease Cytokine Receptors Cytoplasmic Granules Cytoplasmic Vesicles Detection Disease Electron Microscopy Eosinophil Granule Proteins Eosinophil cationic protein Eosinophil-Derived Neurotoxin Exhibits Exocytosis Extracellular Matrix Globulins Health Homeostasis Human Hypersensitivity Immune Immune system Inflammation Interferons Interleukin-4 Investigation Leukocytes Leukotriene C4 Leukotrienes Ligands Lipids Lung Lymphocyte Mediating Methods Molecular Monoclonal Antibodies Pathogenesis Pertussis Toxin Phase Phosphatidylinositols Phosphotransferases Platelet Activating Factor Process Proteins RANTES Research Personnel Role Secretory Vesicles Signal Transduction Site Solid Specificity Stimulus Thymus Gland Tissues Transport Vesicles Vesicle asthmatic airway base chemokine cytokine eosinophil eosinophil peroxidase extracellular granulocyte insight lymph nodes novel novel therapeutic intervention programs receptor response trafficking vesicle-associated membrane protein

项目摘要

DESCRIPTION (provided by applicant): Eosinophils, cells of the innate immune system, have functions in health and in the pathogeneses of asthma, allergies and other diseases. While some functions of eosinophils are based on their acute, effector responses to release preformed granule cationic proteins, other eosinophil functions are based on their regulated release of diverse cytokines that can mediate interactions with other cells in the microenvironment of tissue sites. Eosinophils function in tissues, especially submucosal sites where eosinophils localize even in the absence of disease. Defining eosinophil cytokine-mediated functional interactions between eosinophils and other cells in tissues is germane to understanding eosinophil functions in both ongoing immune homeostasis and acute and chronic diseases. Amongst leukocytes, eosinophils distinctly contain multiple preformed cytokines stored within morphologically unique granules and secretory vesicles. Eosinophils in tissue sites of inflammation, such as asthmatic airways, exhibit ultrastructural alterations indicative of a specific "piecemeal degranulation" process based on vesicular transport, not exocytosis, that releases, with selectivity, specific proteins from eosinophil granules. In contrast to lymphocytes, cells of the adaptive immune system, a special capacity of eosinophils is their potential to rapidly release preformed cytokines; but mechanisms regulating selective release of eosinophil-derived cytokines remain to be delineated. Studies will investigate mechanisms involved in the regulated release of eosinophil-derived proteins, including cytokines. The overall hypothesis is that, central to the functions of eosinophils, the intracellular compartmentalization, trafficking and release of relevant eosinophil proteins, including cytokines, are dependent on regulatory mechanisms that with stimulus dependent specificity can finely regulate the differential and selective secretion of cytokines. Aims are to define: 1) eosinophil vesicle and granule mechanisms involved in cytokine release; 2) intracellular mechanisms for specificity of eosinophil cytokine release; and 3) stimulus-dependent mobilization and release of eosinophil cytokines. Understanding molecular and cellular mechanisms that regulate the extracellular release of eosinophil-derived cytokines will provide insights into eosinophil functions that involve interactions between eosinophils and other cells in tissue sites in the lung and elsewhere and may identify new therapeutic approaches.

描述（由申请人提供）：嗜酸性细胞是先天免疫系统的细胞，在健康和哮喘、过敏和其他疾病的发病机制中起作用。虽然嗜酸性粒细胞的一些功能是基于它们对释放预先形成的颗粒阳离子蛋白的急性效应反应，但其他嗜酸性粒细胞的功能是基于它们对多种细胞因子的调节释放，这些细胞因子可以介导组织部位微环境中与其他细胞的相互作用。嗜酸性粒细胞在组织中起作用，特别是在没有疾病的情况下，嗜酸性粒细胞也存在于粘膜下。确定嗜酸性粒细胞与组织中其他细胞之间由细胞因子介导的功能相互作用，对于理解嗜酸性粒细胞在持续免疫稳态和急慢性疾病中的功能至关重要。在白细胞中，嗜酸性粒细胞明显含有多种预先形成的细胞因子，储存在形态独特的颗粒和分泌囊泡中。炎症组织部位的嗜酸性粒细胞，如哮喘气道，表现出超微结构改变，表明基于囊泡运输的特定“碎片脱粒”过程，而不是胞吐，选择性地从嗜酸性粒细胞颗粒中释放特定蛋白质。与淋巴细胞（适应性免疫系统的细胞）不同，嗜酸性粒细胞的一种特殊能力是它们能够迅速释放预先形成的细胞因子；但是调节嗜酸性粒细胞衍生的细胞因子选择性释放的机制仍有待阐明。研究将探讨涉及调节释放嗜酸性粒细胞衍生蛋白的机制，包括细胞因子。总的假设是，嗜酸性粒细胞功能的核心，细胞内相关嗜酸性粒细胞蛋白（包括细胞因子）的区隔化、运输和释放依赖于调节机制，该机制具有刺激依赖性特异性，可以很好地调节细胞因子的差异和选择性分泌。目的是明确：1)参与细胞因子释放的嗜酸性粒细胞囊泡和颗粒机制；2)嗜酸性细胞因子释放特异性的细胞内机制；3)刺激依赖性的嗜酸性细胞因子的动员和释放。了解调节嗜酸性粒细胞衍生细胞因子的细胞外释放的分子和细胞机制，将有助于深入了解嗜酸性粒细胞与肺和其他组织部位的其他细胞之间的相互作用，并可能确定新的治疗方法。

项目成果

期刊论文数量（20）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Eosinophilia in travelers.

旅行者嗜酸性粒细胞增多。

DOI：
10.1016/s0025-7125(16)30294-2
发表时间：
1992
期刊：
The Medical clinics of North America
影响因子：
0
作者：
Weller,PF
通讯作者：
Weller,PF

Eosinophil-derived cytokines in health and disease: unraveling novel mechanisms of selective secretion.

DOI：
10.1111/all.12103
发表时间：
2013-03
期刊：
Allergy
影响因子：
12.4
作者：
Melo RC;Liu L;Xenakis JJ;Spencer LA
通讯作者：
Spencer LA

The transcription factor XBP1 is selectively required for eosinophil differentiation.

DOI：
10.1038/ni.3225
发表时间：
2015-08
期刊：
Nature immunology
影响因子：
30.5
作者：
Bettigole SE;Lis R;Adoro S;Lee AH;Spencer LA;Weller PF;Glimcher LH
通讯作者：
Glimcher LH

Depletion of eosinophil infiltration by anti-IL-5 monoclonal antibody (TRFK-5) accelerates open skin wound epithelial closure.

DOI：
发表时间：
1997-09
期刊：
The American journal of pathology
影响因子：
0
作者：
James Yang;A. Torio;R. Donoff;G. Gallagher;Robert Egan;P. Weller;David T. W. Wong
通讯作者：
James Yang;A. Torio;R. Donoff;G. Gallagher;Robert Egan;P. Weller;David T. W. Wong

Eosinophils and fibroblasts: the medium in the mesenchyme.

嗜酸性粒细胞和成纤维细胞：间质中的介质。