LTB4 Is a Signal-Relay Molecule during Neutrophil Chemotaxis

Neutrophil recruitment to inflammation sites purportedly depends on sequential waves of chemoattractants. Current models propose that leukotriene B-4 (LTB4), a secondary chemoattractant secreted by neutrophils in response to primary chemoattractants such as formyl peptides, is important in initiating the inflammation process. In this study we demonstrate that LTB4 plays a central role in neutrophil activation and migration to formyl peptides. We show that LTB4 production dramatically amplifies formyl peptide-mediated neutrophil polarization and chemotaxis by regulating specific signaling pathways acting upstream of actin polymerization and Myoll phosphorylation. Importantly, by analyzing the migration of neutrophils isolated from wildtype mice and mice lacking the formyl peptide receptor 1, we demonstrate that LTB4 acts as a signal to relay information from cell to cell over long distances. Together, our findings imply that LTB4 is a signal-relay molecule that exquisitely regulates neutrophil chemotaxis to formyl peptides, which are produced at the core of inflammation sites.