The role of PI3K-delta in neutrophil recruitment

当一个人感染或受伤时，体内就有炎症。被称为中性粒细胞的白细胞将与血管壁(内皮)相互作用，然后进入炎症部位，以对抗那里的细菌，这一过程被称为中性粒细胞募集。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。其中一个这样的信号分子PI3K-Delta可能在细菌感染期间中性粒细胞的募集中发挥重要作用。我们将把化学物质(称为细菌肽和趋化因子，在细菌感染过程中产生)应用于小鼠提睾肌组织以诱导炎症反应，并使用复杂的显微镜系统(称为活体内显微镜)来检查麻醉的、具有正常PI3K-Delta的特殊实验室小鼠和具有不起作用的PI3K-Delta的小鼠发炎肌肉中的中性粒细胞招募。我们还将使用一种特殊的药物，选择性地抑制PI3K-Delta，然后测量炎症肌肉中中性粒细胞的募集。我们有经验和技能使用活体显微镜直接可视化和确定中性粒细胞在血管壁内和跨血管壁以及小鼠组织中的运动。我们将确定PI3K-Delta在中性粒细胞募集的详细过程中的作用，并揭示PI3K-Delta如何在中性粒细胞和内皮细胞中发挥作用，控制中性粒细胞向炎症部位的募集。对PI3K-Delta在中性粒细胞向细菌肽募集中的作用的深入研究，必将为了解PI3K-Delta在细菌感染中中性粒细胞募集中的重要性及其信号机制提供新的知识。这一研究计划的发展和这一领域的额外知识可能会导致针对特定PI3K的新的更好的治疗策略的进步，用于治疗多种炎症和传染病。

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.