title: LTB4 is a signal-relay molecule during neutrophil chemotaxis.
abstract: 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 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 LTB(4) acts as a signal to relay information from cell to cell over long distances. Together, our findings imply that LTB(4) is a signal-relay molecule that exquisitely regulates neutrophil chemotaxis to formyl peptides, which are produced at the core of inflammation sites.
authors.affiliation: Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Philippe V
authors.initials: PV
authors.lastname: Afonso
authors.forename: Mirkka
authors.initials: M
authors.lastname: Janka-Junttila
authors.forename: Young Jong
authors.initials: YJ
authors.lastname: Lee
authors.forename: Colin P
authors.initials: CP
authors.lastname: McCann
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Oliver
authors.forename: Khaled A
authors.initials: KA
authors.lastname: Aamer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Losert
authors.forename: Marcus T
authors.initials: MT
authors.lastname: Cicerone
authors.forename: Carole A
authors.initials: CA
authors.lastname: Parent
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002450:Cell Communication / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology*; D002630:Chemotactic Factors / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D024462:Myosin Type II / Q000378:metabolism; D018375:Neutrophil Activation / Q000276:immunology; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000378:metabolism*; D044042:Receptors, Formyl Peptide / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000199:Actins; D002630:Chemotactic Factors; C469988:Fpr1 protein, mouse; D044042:Receptors, Formyl Peptide; D007975:Leukotriene B4; D024462:Myosin Type II