The role of PI3K-delta in neutrophil recruitment

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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.