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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）：嗜酸性粒细胞，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具有功能。虽然嗜酸性粒细胞的一些功能是基于其释放预先形成的颗粒阳离子蛋白的急性效应器反应，但其他嗜酸性粒细胞功能是基于其调节释放的多种细胞因子，这些细胞因子可以介导与组织部位微环境中其他细胞的相互作用。嗜酸性粒细胞在组织中起作用，特别是在粘膜下部位，即使在没有疾病的情况下嗜酸性粒细胞也位于粘膜下部位。定义嗜酸性粒细胞丝氨酸介导的嗜酸性粒细胞和组织中其他细胞之间的功能相互作用与理解嗜酸性粒细胞在持续的免疫稳态和急性和慢性疾病中的功能密切相关。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（如哮喘气道）中的嗜酸性粒细胞表现出超微结构改变，表明基于囊泡转运而非胞吐的特定“碎片脱颗粒”过程，其选择性地从嗜酸性粒细胞颗粒释放特定蛋白。与淋巴细胞（适应性免疫系统的细胞）相反，嗜酸性粒细胞的特殊能力是其快速释放预先形成的细胞因子的潜力;但调节嗜酸性粒细胞衍生的细胞因子的选择性释放的机制仍有待阐明。研究将调查机制参与调节释放的嗜酸性粒细胞衍生的蛋白质，包括细胞因子。总的假设是，嗜酸性粒细胞的功能，细胞内区室化，运输和相关嗜酸性粒细胞蛋白质，包括细胞因子的释放，是依赖于调节机制，刺激依赖性特异性可以精细地调节细胞因子的差异性和选择性分泌。目的是界定：1）参与细胞因子释放的嗜酸性粒细胞囊泡和颗粒机制; 2）嗜酸性粒细胞因子释放特异性的细胞内机制;和3）嗜酸性粒细胞因子的刺激依赖性动员和释放。了解调节嗜酸性粒细胞衍生的细胞因子的细胞外释放的分子和细胞机制将提供对嗜酸性粒细胞功能的见解，这些功能涉及嗜酸性粒细胞与肺和其他地方的组织部位中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

Hypereosinophilia and recurrent angioneurotic edema in a 2 1/2-year-old girl.

一名 2 1/2 岁女孩嗜酸性粒细胞增多和复发性血管神经性水肿。