Role of signal regulatory protein in neutrophil function

信号调节蛋白在中性粒细胞功能中的作用

• 批准号: 6684457
• 负责人: CHARLES A PARKOS
• 金额: $ 38万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6684457
• 关键词: CD antigens; cell migration; cell surface receptors; chemoattractants; clinical research; epitope mapping; human subject; immunopathology; immunoprecipitation; inflammation; laboratory mouse; membrane proteins; membrane transport proteins; monoclonal antibody; mucosa; neutrophil; peptide library; phosphorylation; protein binding; protein localization; receptor binding; transfection

DESCRIPTION (provided by applicant): Neutrophil (PMN) migration within tissues is a central component of both host defense and many pathophysiologic processes. While many studies have focused on defining events involved in the regulation of PMN migration at the level of the cell surface, the sequence of events that serve to fine-tune PMN migration during the inflammatory response are incompletely understood. Perhaps even less well appreciated is how the pathways controlling PMN migration contribute to pathologic inflammation. Indeed, a variety of human diseases, in their active and symptomatic stages, are characterized by migration of large numbers of neutrophils (PMN) through tissues and across mucosal surfaces. Recent studies from our group investigating the mechanisms of PMN migration across mucosal surfaces demonstrated an important role of a membrane protein termed CD47 in regulating the rate of PMN migration. As outlined in this proposal, we have evidence demonstrating that CD47 binding to a cellular receptor termed signal regulatory protein (SIRPa) regulates the rate of PMN migration. Furthermore, we have data suggesting that several SIRPa proteins are present within different subcellular compartments in PMN. The overall goal of this proposal is define these PMN SIRP proteins and their role(s) in regulating PMN migration. To achieve this goal, we will identify region(s) on SIRPa that are involved in modulation of PMN migration, characterize SIRP proteins that are expressed in PMN and define their cellular distributions during chemoattractant stimulation. Information from the proposed studies will provide new insights into the role of SIRPs in the regulation of PMN migration and may yield new ideas for therapeutics aimed at inhibiting pathologic inflammation.

描述（由申请人提供）：组织内的中性粒细胞（PMN）迁移是宿主防御和许多病理生理过程的核心组成部分。虽然许多研究集中于在细胞表面水平上定义参与 PMN 迁移调节的事件，但在炎症反应期间用于微调 PMN 迁移的事件序列尚不完全清楚。也许更不为人所知的是控制中性粒细胞迁移的途径如何导致病理性炎症。事实上，多种人类疾病在其活动期和症状期的特征是大量中性粒细胞（PMN）通过组织和粘膜表面迁移。我们小组最近研究 PMN 跨粘膜表面迁移机制的研究表明，一种名为 CD47 的膜蛋白在调节 PMN 迁移速率中发挥着重要作用。正如本提案所述，我们有证据表明 CD47 与称为信号调节蛋白 (SIRPa) 的细胞受体结合可调节 PMN 迁移速率。此外，我们有数据表明几种 SIRPa 蛋白存在于 PMN 的不同亚细胞区室中。该提案的总体目标是定义这些 PMN SIRP 蛋白及其在调节 PMN 迁移中的作用。为了实现这一目标，我们将识别 SIRPa 上参与调节 PMN 迁移的区域，表征在 PMN 中表达的 SIRP 蛋白，并定义它们在趋化剂刺激期间的细胞分布。拟议研究的信息将为 SIRP 在 PMN 迁移调节中的作用提供新的见解，并可能为旨在抑制病理性炎症的治疗产生新的思路。