ABSTRACT: Neutrophil recruitment to sites of injury or infection is essential for host defense, but it needs to be tightly regulated to prevent tissue damage. Phosphoinositide 3-kinase (PI3K), which generates the phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P(3)], is necessary for neutrophil motility in vivo; however, the role of SH2-domain-containing 5-inositol phosphatase (SHIP) enzymes, which hydrolyze PI(3,4,5)P(3) to phosphatidylinositol 3,4-bisphosphate [PI(3,4)P(2)], is not well understood. Here we show that SHIP phosphatases limit neutrophil motility in live zebrafish. Using real-time imaging of bioprobes specific for PI(3,4,5)P(3) and PI(3,4)P(2) in neutrophils, we found that PI(3,4,5)P(3) and PI(3,4)P(2) accumulate at the leading edge while PI(3,4)P(2) also localizes to the trailin
