GLYCOLIPID E-SELECTIN LIGANDS ON HUMAN GRANULOCYTES
人粒细胞上的糖脂 E-选择素配体
基本信息
- 批准号:6497278
- 负责人:
- 金额:$ 33.37万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2000
- 资助国家:美国
- 起止时间:2000-02-15 至 2004-01-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Inflammation involves extensive granulocyte extravasation from the blood into tissues at a site of infection or immunologic challenge. Adhesion molecules and complementary ligands on granulocytes and on the blood vessel wall endothelium control the extent and identity of granulocytes entering the tissue at a site of insult. E-selectin, expressed de novo on activated endothelial cells, is a selectin adhesion protein which mediates cell-cell adhesion early in this immune response by binding to leukocyte surface glycoconjugates. The identification of normal human granulocyte glycoconjugates responsible for E-selectin-mediated cell adhesion will be important to the understanding of inflammation in its many forms, and may offer novel avenues for inflammation control. Although several glycoconjugates which bind to selectins have been identified, the natural ligands for E-selectin on human granulocytes have yet to be fully elucidated. The applicants and others have obtained strong published and preliminary data indicating that glycosphingolipids on normal human neutrophils and eosinophils, not glycoproteins, are the most important legends for E-selectin, and that these glycosphingolipids may differ from those previously identified in cell lines such as HL-60. This proposal combines expertise from three laboratories in granulocyte cell adhesion under both static and physiologic flow conditions with glycosphingolipid glycobiology to evaluate the roles of normal human granulocyte glycosphingolipids in E-selectin binding and granulocyte function. Aim 1 tests the hypothesis that glycosphingolipids constitute major ligands for E-selectin on intact normal human neutrophils and eosinophils using cell adhesion assays and highly specific enzymes, antibodies, and glycoconjugate biosynthesis inhibitors. Aim 2 uses methods for glycosphingolipid extraction, resolution and functional analysis to isolate and identify glycosphingolipids from normal peripheral blood neutrophils and eosinophils capable of specific binding to E-selectin. TLC analysis, antibodies, specific enzymes, and matrix assisted laser desorption ionization mass spectroscopy will be used to elucidate and characterize the structures of these glycosphingolipids. Aim 3 will test glycosphingolipids on intact cells, and glycosphingolipids identified from Aim 2, for their roles in granulocyte cell adhesion under static conditions and physiological flow, and will allow us to test whether these glycosphingolipids are the natural ligands for E-selectin on normal human granulocytes. Knowledge gained from these studies will advance the design of improved anti-inflammatory drugs, and our understanding of the physiological roles of glycosphingolipids in leukocyte adhesion.
炎症涉及大量粒细胞从血液外渗到感染或免疫激发部位的组织中。 粒细胞和血管壁内皮上的粘附分子和互补配体控制粒细胞在损伤部位进入组织的程度和身份。 E-选择素在活化的内皮细胞上重新表达,是一种选择素粘附蛋白,它通过与白细胞表面糖缀合物结合来介导免疫反应早期的细胞-细胞粘附。 鉴定负责E-选择素介导的细胞粘附的正常人粒细胞糖缀合物对于理解多种形式的炎症将是重要的,并可能为炎症控制提供新的途径。虽然已经鉴定了几种与选择素结合的糖缀合物,但人粒细胞上E-选择素的天然配体尚未完全阐明。 申请人和其他人已经获得了强有力的公开和初步数据,表明正常人嗜中性粒细胞和嗜酸性粒细胞上的鞘糖脂,而不是糖蛋白,是E-选择素的最重要的图例,并且这些鞘糖脂可能不同于先前在细胞系如HL-60中鉴定的鞘糖脂。 该提案结合了三个实验室在静态和生理流动条件下粒细胞粘附与鞘糖脂糖生物学的专业知识,以评估正常人粒细胞鞘糖脂在E-选择素结合和粒细胞功能中的作用。目的1测试的假设,鞘糖脂构成的主要配体E-选择素对完整的正常人中性粒细胞和嗜酸性粒细胞使用细胞粘附试验和高度特异性的酶,抗体和糖缀合物生物合成抑制剂。目的2采用鞘糖脂的提取、拆分和功能分析方法,从正常外周血中性粒细胞和嗜酸性粒细胞中分离和鉴定能够特异性结合E-选择素的鞘糖脂。 TLC分析、抗体、特异性酶和基质辅助激光解吸电离质谱将用于阐明和表征这些鞘糖脂的结构。 目标3将测试完整细胞上的鞘糖脂,以及从目标2中鉴定的鞘糖脂,它们在静态条件和生理流动下在粒细胞粘附中的作用,并将使我们能够测试这些鞘糖脂是否是正常人粒细胞上E-选择素的天然配体。从这些研究中获得的知识将促进改进的抗炎药物的设计,以及我们对鞘糖脂在白细胞粘附中的生理作用的理解。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Bruce S Bochner其他文献
Bruce S Bochner的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Bruce S Bochner', 18)}}的其他基金
Exploiting Siglec-6 for targeted anti-allergy drug delivery into human mast cells
利用 Siglec-6 将靶向抗过敏药物输送到人体肥大细胞中
- 批准号:
10368109 - 财政年份:2021
- 资助金额:
$ 33.37万 - 项目类别:
Exploiting Siglec-6 for targeted anti-allergy drug delivery into human mast cells
利用 Siglec-6 将靶向抗过敏药物输送到人体肥大细胞中
- 批准号:
10194041 - 财政年份:2021
- 资助金额:
$ 33.37万 - 项目类别:
Using siglecs and their ligands to treat allergic diseases SALTAD
使用siglecs及其配体治疗过敏性疾病SALTAD
- 批准号:
10331722 - 财政年份:2018
- 资助金额:
$ 33.37万 - 项目类别:
Defining Siglec-6 and Siglec-8 function on effector cells of allergic diseases
定义 Siglec-6 和 Siglec-8 对过敏性疾病效应细胞的功能
- 批准号:
10097994 - 财政年份:2018
- 资助金额:
$ 33.37万 - 项目类别:
Using siglecs and their ligands to treat allergic diseases SALTAD
使用siglecs及其配体治疗过敏性疾病SALTAD
- 批准号:
10097976 - 财政年份:2018
- 资助金额:
$ 33.37万 - 项目类别:
Defining Siglec-6 and Siglec-8 function on effector cells of allergic diseases
定义 Siglec-6 和 Siglec-8 对过敏性疾病效应细胞的功能
- 批准号:
10331725 - 财政年份:2018
- 资助金额:
$ 33.37万 - 项目类别:
相似海外基金
The formation and degradation of neutrophil and eosinophil extracellular traps in otitis media
中耳炎中中性粒细胞和嗜酸性粒细胞胞外陷阱的形成和降解
- 批准号:
23K08953 - 财政年份:2023
- 资助金额:
$ 33.37万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Role of eosinophil cationic proteins in cardiac hypertrophy
嗜酸性粒细胞阳离子蛋白在心脏肥大中的作用
- 批准号:
10735136 - 财政年份:2023
- 资助金额:
$ 33.37万 - 项目类别:
Role of GATA2-RPN1 intergenic region common variants in eosinophil/basophil regulation
GATA2-RPN1基因间区域常见变异在嗜酸性粒细胞/嗜碱性粒细胞调节中的作用
- 批准号:
23K06375 - 财政年份:2023
- 资助金额:
$ 33.37万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
12th Biennial Symposium of the International Eosinophil Society, Inc. (IES)
国际嗜酸性粒细胞学会 (IES) 第 12 届双年研讨会
- 批准号:
10682801 - 财政年份:2023
- 资助金额:
$ 33.37万 - 项目类别:
Anti-eosinophil Gene Therapy for Eosinophilic Esophagitis
抗嗜酸性粒细胞基因治疗嗜酸性粒细胞性食管炎
- 批准号:
10481279 - 财政年份:2022
- 资助金额:
$ 33.37万 - 项目类别:
The regulatory mechanism of sympathetic nerves on eosinophil-associated micr o-inflammation in animals with IBS
交感神经对IBS动物嗜酸性粒细胞相关微炎症的调节机制
- 批准号:
22K15656 - 财政年份:2022
- 资助金额:
$ 33.37万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Basic research on eosinophil subsets to aim a precision medicine for severe eosinophilic asthma
嗜酸性粒细胞亚群的基础研究旨在针对严重嗜酸性粒细胞哮喘的精准治疗
- 批准号:
21K08218 - 财政年份:2021
- 资助金额:
$ 33.37万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Function of the IL-18-IL-18R1-IFN-T2 Cytokine Eosinophil Axis in Asthma
IL-18-IL-18R1-IFN-T2 细胞因子嗜酸性粒细胞轴在哮喘中的功能
- 批准号:
10311950 - 财政年份:2021
- 资助金额:
$ 33.37万 - 项目类别:
Development of a Treatment for Eosinophil-Mediated Allergic Inflammatory Diseases Utilizing a Neutralizing Agent Targeting Eosinophil Granule Major Basic Protein
利用针对嗜酸性粒细胞颗粒主要碱性蛋白的中和剂开发治疗嗜酸性粒细胞介导的过敏性炎症疾病的方法
- 批准号:
10401936 - 财政年份:2021
- 资助金额:
$ 33.37万 - 项目类别:
Mechanisms of eosinophil-associated heart disease
嗜酸性粒细胞相关心脏病的机制
- 批准号:
10117454 - 财政年份:2021
- 资助金额:
$ 33.37万 - 项目类别: