Resolution of inflammation by retrograde chemotaxis of neutrophils in transgenic zebrafish

Abstract: Neutrophil chemotaxis to sites of in-flammation is a critical process during normal im-mune responses to tissue injury and infection and pathological immune responses leading to chronic inflammation. Although progress has been made in understanding the mechanisms that promote neu-trophil recruitment to inflamed tissue, the mecha-nisms that regulate the resolution phase of the in-flammatory response have remained relatively elu-sive. To define the mechanisms that regulate neutrophil-mediated inflammation in vivo, we have developed a novel transgenic zebrafish in which the neutrophils express GFP under control of the my-eloperoxidase promoter (zMPO:GFP). Tissue in-jury induces a robust, inflammatory response, which is characterized by the rapid chemotaxis of neutrophils to the wound site. In vivo time-lapse imaging shows that neutrophils subsequently dis-play directed retrograde chemotaxis back toward the vasculature. These findings implicate retro-grade chemotaxis as a novel mechanism that regu-lates the resolution phase of the inflammatory re-sponse. The zMPO:GFP zebrafish provides unique insight into the mechanisms of neutrophil-mediated inflammation and thereby offers opportunities to identify new regulators of the inflammatory re