The role of PI3K-delta in neutrophil recruitment

PI3K-delta 在中性粒细胞募集中的作用

• 批准号: 386732-2010
• 负责人: Liu, Lixin
• 金额: $ 1.97万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2010
• 资助国家: 加拿大
• 起止时间: 2010-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=463929
• 关键词: role; PI3K; delta; neutrophil; recruitment

When a person has an infection or injury, there is inflammation in the body. White blood cells called neutrophils will interact with and then move out of the blood vessel wall (endothelium) into the inflammation site to fight the bacteria there, a process called neutrophil recruitment. This process is controlled by many signaling molecules, some of which are inside neutrophils and also within endothelium. One such signaling molecule PI3K-delta may be important in neutrophil recruitment during bacterial infections. We will apply chemicals (called bacterial peptides and chemokines, that are produced during bacterial infections) to the mouse cremaster muscle tissue to induce an inflammatory response and use a sophisticated microscope system (called intravital microscopy) to examine neutrophil recruitment in the inflamed muscle in anesthetized, special laboratory mice having normal PI3K-delta and mice having non-functional PI3K-delta. We will also use a special drug that selectively inhibits PI3K-delta and then measure the neutrophil recruitment in the inflamed muscle. We have the experience and skills of using intravital microscopy to directly visualize and determine the movement of neutrophils within and across the blood vessel wall and in the tissues in mice. We will determine the role of PI3K-delta in the detailed process of neutrophil recruitment and reveal how PI3K-delta works in neutrophils and in endothelium to control neutrophil recruitment to the inflammation site. Insights gained on the role of PI3K-delta in neutrophil recruitment toward bacterial peptides will certainly provide new knowledge on the importance of PI3K-delta and its signaling mechanisms in neutrophil recruitment during bacterial infections. The development of this research program and the added knowledge in this area may lead to the advancement of new and better therapeutic strategies targeting specific PI3K for the treatment of numerous inflammatory and infectious diseases.

当一个人感染或受伤时，体内会有炎症。称为中性粒细胞的白色血细胞将与血管壁（内皮）相互作用，然后移出血管壁（内皮）进入炎症部位，以对抗那里的细菌，这一过程称为中性粒细胞招募。 这一过程由许多信号分子控制，其中一些在中性粒细胞内，也在内皮细胞内。 一种这样的信号分子PI 3 K-delta可能在细菌感染期间的中性粒细胞募集中很重要。 我们将应用化学物质（称为细菌肽和趋化因子，在细菌感染过程中产生）到小鼠提睾肌组织中以诱导炎症反应，并使用复杂的显微镜系统（称为活体显微镜）来检查具有正常PI 3 K-delta的麻醉特殊实验室小鼠和具有非功能性PI 3 K-delta的小鼠中炎症肌肉中的中性粒细胞募集。 我们还将使用一种特殊的药物，选择性地抑制PI 3 K-delta，然后测量炎症肌肉中的中性粒细胞募集。 我们有使用活体显微镜直接观察和确定中性粒细胞在小鼠血管壁和组织中的运动的经验和技能。 我们将确定PI 3 K-delta在中性粒细胞募集的详细过程中的作用，并揭示PI 3 K-delta如何在中性粒细胞和内皮细胞中起作用，以控制中性粒细胞募集到炎症部位。 关于PI 3 K-delta在中性粒细胞向细菌肽募集中的作用的见解肯定会提供关于PI 3 K-delta及其在细菌感染期间中性粒细胞募集中的信号传导机制的重要性的新知识。 这项研究计划的发展和在这一领域增加的知识可能会导致新的和更好的治疗策略的进展，针对特定的PI 3 K治疗许多炎症和感染性疾病。