MAST CELL GRANULES INDUCE ENDOTHELIAL CELL MOTILITY
肥大细胞颗粒诱导内皮细胞运动
基本信息
- 批准号:2638045
- 负责人:
- 金额:$ 26.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-01-01 至 1999-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (Adapted from Investigator's Abstract): This is a revised
application examining the role of mast cells and adherent junctions in
endothelial motility. Endothelial motility is critical to the formation of
blood vessels during development, tumor formation, and in response to
ischemia as well as an integral part of the response of the arterial wall to
injury and atherosclerotic stimuli. The formation of blood vessels during
regeneration, healing and tumor formation requires new vessels to form from
old, and interruption of the continuity of existing endothelium requires
re-establishment of the integrity of the endothelium. Both these processes
require the release of endothelial cells from the joint inhibitions on cell
movement and cell division characteristic of a stable, confluent sheet of
endothelial cells. This investigator has observed that secretory granules
from mast cells, when added to confluent monolayers of cultured endothelial
cells, have the ability to restore motility to immotile endothelial cells in
a confluent monolayer. Their evidence indicates that the component of the
granule principally responsible for this activity is heparin proteoglycan.
The free glycosaminoglycan form of heparin has no activity but can block the
activity of granules. The regained motility of the cells induced by
granules is associated with the formation of substantial gaps in the
monolayer as the cells move. This proposal is based upon the finding that
secretory granules from mast cells restore motility to immotile endothelial
cells in confluent monolayers. The proposal hypothesizes that changes in
proteins comprising adherent junctions (e.g., cadherin-5, catenins, p120,
ZO-1, moesin, and ezrin) are responsible for the down regulation of motility
following the establishment of confluent endothelial monolayers and the
upregulation induced by mast cell granules or by bFGF. The extensively
revised proposal uses a combination of confocal microscopy and protein
quantification to examine the regulation of these proteins and to correlate
them with changes in cell motility. Seven specific aims are proposed,
including four new Aims. Aim 1 will correlate the display of cadherin-5 and
associated proteins in adherent junctions with motility induced by mast cell
granules and by bFGF. Aim 2 will examine the distribution of cadherin-5 in
the cytoskeletal-bound state and the soluble cytoplasmic state. Four new
aims will determine if changes observed in Aims 1 and 2 are related to
tyrosine phosphorylation, develop tests of the functional state of adherent
junctions to determine if motility is associated with weakening of the
junctions, and determine in bFGF contributes to the effects of mass cell
granules. A final Aim (7), will compare large vessel and microvascular
endothelial cells.
描述(改编自研究者摘要):这是一份修订版
应用检查肥大细胞和粘附连接在
内皮运动 内皮细胞的运动性对血管内皮细胞的形成至关重要。
血管在发展过程中,肿瘤形成,并在响应
以及动脉壁对缺血的反应的组成部分,
损伤和动脉粥样硬化刺激。 血管的形成
再生,愈合和肿瘤形成需要新的血管形成,
旧的,和现有内皮细胞的连续性中断需要
重建内皮的完整性。 这两个过程
需要内皮细胞从对细胞的联合抑制中释放出来,
稳定、融合的细胞片的运动和细胞分裂特征
内皮细胞 研究者观察到分泌颗粒
从肥大细胞,当加入到培养的内皮细胞的汇合单层,
细胞,有能力恢复运动的不动内皮细胞,
融合的单层细胞。 他们的证据表明,
主要负责这种活性的颗粒是肝素蛋白聚糖。
肝素的游离糖胺聚糖形式没有活性,但可以阻断
颗粒的活性。 诱导的细胞运动性恢复
颗粒的形成与颗粒中大量间隙的形成有关。
随着细胞的移动, 这一建议的依据是,
肥大细胞分泌颗粒恢复不动内皮细胞的运动
融合单层细胞。 该提案假设,
包含粘附连接的蛋白质(例如,钙粘蛋白-5,连环蛋白,p120,
ZO-1、膜突蛋白和埃兹蛋白)负责运动性的下调
在建立汇合的内皮单层和
通过肥大细胞颗粒或bFGF诱导的上调。 广泛地
修订后的建议使用共聚焦显微镜和蛋白质的组合
定量检测这些蛋白质的调节,
它们与细胞运动性的变化有关。 提出了七个具体目标,
包括四个新目标。 目的1将钙粘蛋白-5的显示与
粘附连接相关蛋白与肥大细胞诱导的运动
颗粒和bFGF。 目的2将检查钙粘蛋白-5在人乳腺癌组织中的分布。
胞质结合状态和可溶性胞质状态。 四个新
目标1和2中观察到的变化是否与以下方面有关:
酪氨酸磷酸化,开发粘附功能状态的测试
连接,以确定运动性是否与减弱的
连接,并确定在bFGF有助于质量细胞的影响,
颗粒。 最终目标(7)将比较大血管和微血管
内皮细胞
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)
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David Lagunoff其他文献
David Lagunoff的其他文献
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{{ truncateString('David Lagunoff', 18)}}的其他基金
Live Cell Imaging Confocal Microscope with Spectral Detector and Resonant Scanner
带光谱探测器和共振扫描仪的活细胞成像共焦显微镜
- 批准号:
8051254 - 财政年份:2011
- 资助金额:
$ 26.91万 - 项目类别:
MAST CELL GRANULES INDUCE ENDOTHELIAL CELL MOTILITY
肥大细胞颗粒诱导内皮细胞运动
- 批准号:
2029385 - 财政年份:1997
- 资助金额:
$ 26.91万 - 项目类别:
MAST CELL GRANULES INDUCE ENDOTHELIAL CELL MOTILITY
肥大细胞颗粒诱导内皮细胞运动
- 批准号:
2857851 - 财政年份:1997
- 资助金额:
$ 26.91万 - 项目类别:
MINORITY HIGH SCHOOL STUDENT RESEARCH APPRENTICE PROGRAM
少数民族高中生研究学徒计划
- 批准号:
3513052 - 财政年份:1991
- 资助金额:
$ 26.91万 - 项目类别:
MINORITY HIGH SCHOOL STUDENT RESEARCH APPRENTICE PROGRAM
少数民族高中生研究学徒计划
- 批准号:
2282763 - 财政年份:1991
- 资助金额:
$ 26.91万 - 项目类别:
MINORITY HIGH SCHOOL STUDENT RESEARCH APPRENTICE PROGRAM
少数民族高中生研究学徒计划
- 批准号:
3513051 - 财政年份:1991
- 资助金额:
$ 26.91万 - 项目类别:
MINORITY HIGH SCHOOL STUDENT RESEARCH APPRENTICE PROGRAM
少数民族高中生研究学徒计划
- 批准号:
2282764 - 财政年份:1991
- 资助金额:
$ 26.91万 - 项目类别:
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