GLYCOSAMINOGLYCAN-CHEMOKINE INTERACTIONS BY NMR & MASS SPECTROMETRY

通过 NMR 测定糖胺聚糖-趋化因子相互作用

• 批准号: 8361817
• 负责人: JAMES H. PRESTEGARD
• 金额: $ 0.18万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361817
• 关键词: Atherosclerosis; Binding; Blood Vessels; CCL2 gene; CCL7 gene; Cell Surface Receptors; Cells; Development; Disease; Event; Family; Foam Cells; Funding; G-Protein-Coupled Receptors; Glycosaminoglycans; Grant; Human; Immune; Immune response; Inflammatory Response; Investigation; Maintenance; Malignant Neoplasms; Mass Spectrum Analysis; Membrane; Methodology; Movement; National Center for Research Resources; Neoplasm Metastasis; Physiological Processes; Play; Principal Investigator; Proteins; RANTES; Recruitment Activity; Research; Research Infrastructure; Resources; Role; Shapes; Side; Signal Transduction; Site; Source; System; Tissues; United States National Institutes of Health; angiogenesis; cell motility; chemokine; cost; macrophage; monocyte; neoplastic cell; tumor; tumor growth

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Human chemokines comprise a family of approximately 50 small soluble proteins that interact with about 20 cell surface receptors to regulate cellular migration and signaling events. Many are involved in recruitment and stimulation of immune cells as a part of inflammatory response, but others regulate cell migration during development. While their signaling functions occur through interactions with specific membrane bound G protein-coupled receptors, these interactions are often modulated by interactions with glycosaminoglycans (GAGs). The latter interactions are also believed to be important in the maintenance of gradients of chemokine concentrations necessary for directing the migration of cells to their sites of action, and for the assisted movement of chemokines from the tissue to the luminal side of vascular endothelial layers. The specific targets for this investigation are CCL2 and CCL7. These chemokines are involved in recruitment of monocytes and macrophages in normal physiological processes as well as several diseases. For example, CCL2 recruits CCR2 expressing monocytes into damaged arterial vessels, which then become resident foam cells that promote the development of atherosclerosis. CCL2 also plays a role in cancer. Many tumor cells produce CCL2 to recruit "tumor-associated macrophages" (TAMs) that shape the microenvironment to a state conducive to tumor growth by suppressing the adaptive immune response, and by promoting angiogenesis and metastasis. The Resource is using the NMR and MS methodology it has developed for the CCL5 system to investigate the interaction of CCL2 and CCL7 with various GAG oligomers.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 人类趋化因子由大约 50 种小可溶性蛋白质组成，它们与大约 20 种细胞表面受体相互作用，调节细胞迁移和信号传导事件。 作为炎症反应的一部分，许多细胞参与免疫细胞的招募和刺激，但其他细胞则在发育过程中调节细胞迁移。 虽然它们的信号传导功能是通过与特定膜结合 G 蛋白偶联受体的相互作用来实现的，但这些相互作用通常通过与糖胺聚糖 (GAG) 的相互作用来调节。后一种相互作用也被认为对于维持趋化因子浓度梯度很重要，这对于引导细胞迁移到其作用位点以及辅助趋化因子从组织移动到血管内皮层的管腔侧是必需的。本次调查的具体目标是CCL2和CCL7。 这些趋化因子参与正常生理过程以及多种疾病中单核细胞和巨噬细胞的募集。 例如，CCL2 将表达 CCR2 的单核细胞招募到受损的动脉血管中，然后这些单核细胞成为促进动脉粥样硬化发展的常驻泡沫细胞。 CCL2 在癌症中也发挥着作用。 许多肿瘤细胞产生 CCL2 来招募“肿瘤相关巨噬细胞”(TAM)，通过抑制适应性免疫反应、促进血管生成和转移，将微环境塑造成有利于肿瘤生长的状态。 该资源正在使用其为 CCL5 系统开发的 NMR 和 MS 方法来研究 CCL2 和 CCL7 与各种 GAG 低聚物的相互作用。