[PDF][PDF] LTB4 is a signal-relay molecule during neutrophil chemotaxis

PV Afonso, M Janka-Junttila, YJ Lee, CP McCann… - Developmental cell, 2012 - cell.com
PV Afonso, M Janka-Junttila, YJ Lee, CP McCann, CM Oliver, KA Aamer, W Losert
Developmental cell, 2012cell.com
Neutrophil recruitment to inflammation sites purportedly depends on sequential waves of
chemoattractants. Current models propose that leukotriene B 4 (LTB 4), 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 LTB 4 plays a central role in neutrophil activation and migration to formyl
peptides. We show that LTB 4 production dramatically amplifies formyl peptide-mediated …
Summary
Neutrophil recruitment to inflammation sites purportedly depends on sequential waves of chemoattractants. Current models propose that leukotriene B4 (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 MyoII phosphorylation. Importantly, by analyzing the migration of neutrophils isolated from wild-type 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.
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