Download or read book Cell Signaling and Cytoskeletal Regulation in Neutrophil Cell Migration in Vivo written by and published by . This book was released on 2014 with total page 305 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neutrophils are the most abundant white blood cells and their recruitment to sites of injury or infection is essential for host defense. Abnormal infiltration of neutrophils is the hallmark of inflammatory disease. The activation and regulation of neutrophil chemotaxis must be precise in order to prevent abnormal situations leading to disease states. In this dissertation, I use zebrafish as an italicin vivoitalic model to delineate the cell signaling and cytoskeletal regulation of neutrophil interstitial migration and innate immune response. In particular, I elucidate two negative regulators of neutrophil motility, the SH2-domain-containing inositol 5-phosphatase (SHIP) and microtubules. Phosphoinositide 3-kinase (PI3K), which generates the phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P(3)], is necessary for neutrophil motility italicin vivoitalic; however, the role of SHIP enzymes, which hydrolyze PI(3,4,5)P(3) to phosphatidylinositol 3,4-bisphosphate [PI(3,4)P(2)], is not well understood. In Chapter 2, I demonstrate that SHIPs control neutrophil inflammation and limit neutrophil motility by modulating PI3K signaling. The role of microtubules in regulating leukocyte migration is also not clear. In Chapter 3, I illustrate that microtubule depolymerization inhibits polarized PI3K activation at the leading edge of neutrophils, inducing PI3K independent motility but negatively impacting neutrophil directional migration. Our data also suggest that microtubules exert their effects on neutrophil polarity and motility at least in part by the negative regulation of both Rho and Rac activities. Next, in Chapter 4, I demonstrate that the routine heat shock method used for inducible gene expression in animal models with common heat shock promoters can alter neutrophil function in zebrafish. My findings suggest that caution must be taken when employing a heat shock-dependent inducible system to study the innate immune response and that data arising from such experiments need to be carefully scrutinized. Together, my thesis research provides a better understanding of the signaling mechanisms involved in regulating neutrophil migration and function italicin vivoitalic.