GLYCOSAMINOGLYCAN-CHEMOKINE INTERACTIONS BY NMR & MASS SPECTROMETRY

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 人趋化因子包括约50种小的可溶性蛋白质的家族，其与约20种细胞表面受体相互作用以调节细胞迁移和信号传导事件。 许多参与招募和刺激免疫细胞作为炎症反应的一部分，但其他人在发育过程中调节细胞迁移。 虽然它们的信号传导功能通过与特异性膜结合G蛋白偶联受体的相互作用发生，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。后者的相互作用也被认为在维持趋化因子浓度梯度方面是重要的，趋化因子浓度梯度对于引导细胞迁移到其作用位点以及对于趋化因子从组织到血管内皮层的腔侧的辅助移动是必要的。本次调查的具体目标是CCL 2和CCL 7。 这些趋化因子参与正常生理过程以及几种疾病中单核细胞和巨噬细胞的募集。 例如，CCL 2将表达CCR 2的单核细胞募集到受损的动脉血管中，然后成为促进动脉粥样硬化发展的常驻泡沫细胞。 CCL 2也在癌症中发挥作用。 许多肿瘤细胞产生CCL 2以募集“肿瘤相关巨噬细胞”（TAM），其通过抑制适应性免疫应答以及通过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CCL 5系统开发的NMR和MS方法来研究CCL 2和CCL 7与各种GAG低聚物的相互作用。

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.