title: Annexin 1 mediates the rapid anti-inflammatory effects of neutrophil-derived microparticles.
abstract: Polymorphonuclear leukocyte (PMN)-derived microparticles display inhibitory properties on target cells as assessed in vitro; since PMNs contain abundant amounts of the endogenous anti-inflammatory protein annexin 1 (AnxA1), we tested here whether biologically active AnxA1 could be present in PMN-derived microparticles. PMN adhesion to human umbilical vein endothelial cell (HUVEC) monolayers led to the generation of microparticles that contained AnxA1, as detected by Western blotting, flow cytometry, and mass spectrometry analyses. Addition of these microparticles to recipient PMNs prior to flow over HUVEC monolayers significantly inhibited cell adhesion, an effect abrogated by a neutralizing anti-AnxA1 antibody, or an antibody raised against the AnxA1 receptor, that is termed lipoxin A(4) receptor or ALX. Intravenous delivery of human PMN-derived microparticles markedly inhibited PMN recruitment to an air pouch inflamed with IL-1beta. This anti-inflammatory effect was also dependent on endogenous AnxA1, since injection of microparticles produced from wild-type PMNs (bone marrow derived), but not from AnxA1-null PMNs, inhibited IL-1beta-induced leukocyte trafficking. In conclusion, PMN-derived microparticles contain functionally active AnxA1 that confers them anti-inflammatory properties; generation of these microparticles in the microcirculation could promote inflammatory resolution by time-dependent dampening of cell recruitment.
authors.affiliation: The William Harvey Research Institute, Barts and The London Medical School, London, United Kingdom.
authors.forename: Jesmond
authors.initials: J
authors.lastname: Dalli
authors.forename: Lucy V
authors.initials: LV
authors.lastname: Norling
authors.forename: Derek
authors.initials: D
authors.lastname: Renshaw
authors.forename: Dianne
authors.initials: D
authors.lastname: Cooper
authors.forename: Kit-Yi
authors.initials: KY
authors.lastname: Leung
authors.forename: Mauro
authors.initials: M
authors.lastname: Perretti
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007249:Inflammation; D018836:Inflammation Mediators; D051379:Mice; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology / Q000648:ultrastructure*
chemical_list: D017305:Annexin A1; D018836:Inflammation Mediators