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: 7086257
• 负责人: CHARLES A PARKOS
• 金额: $ 37.11万
• 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 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7086257
• 关键词: CD47 molecule; 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。尽管许多研究的重点是定义在细胞表面水平上调节PMN迁移的事件，但在炎症反应过程中用于微调PMN迁移的事件序列尚不完全了解。也许不太受欢迎的是控制PMN迁移的途径如何导致病理炎症。实际上，各种人类疾病在其活跃和有症状的阶段中的特征是大量中性粒细胞（PMN）通过组织和跨粘膜表面迁移。我们小组研究了PMN跨粘膜表面的机制的最新研究表明，称为CD47的膜蛋白在调节PMN迁移速率中起着重要作用。如本提案中概述的那样，我们有证据表明CD47与称为信号调节蛋白（SIRPA）的细胞受体结合可以调节PMN迁移速率。此外，我们有数据表明，在PMN的不同亚细胞室内存在几种siRPA蛋白。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，我们将确定与PMN迁移调节有关的SIRPA上的区域，表征了SIRP蛋白，这些SIRP蛋白在PMN中表达并定义其在化学吸引力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炎症的治疗疗法产生新的想法。