title: The junctional adhesion molecule JAM-C regulates polarized transendothelial migration of neutrophils in vivo.
abstract: The migration of neutrophils into inflamed tissues is a fundamental component of innate immunity. A decisive step in this process is the polarized migration of blood neutrophils through endothelial cells (ECs) lining the venular lumen (transendothelial migration (TEM)) in a luminal-to-abluminal direction. By real-time confocal imaging, we found that neutrophils had disrupted polarized TEM ('hesitant' and 'reverse') in vivo. We noted these events in inflammation after ischemia-reperfusion injury, characterized by lower expression of junctional adhesion molecule C (JAM-C) at EC junctions, and they were enhanced by blockade or genetic deletion of JAM-C in ECs. Our results identify JAM-C as a key regulator of polarized neutrophil TEM in vivo and suggest that reverse TEM of neutrophils can contribute to the dissemination of systemic inflammation.
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK.
authors.forename: Abigail
authors.initials: A
authors.lastname: Woodfin
authors.forename: Mathieu-Benoit
authors.initials: MB
authors.lastname: Voisin
authors.forename: Martina
authors.initials: M
authors.lastname: Beyrau
authors.forename: Bartomeu
authors.initials: B
authors.lastname: Colom
authors.forename: Dorothée
authors.initials: D
authors.lastname: Caille
authors.forename: Frantzeska-Maria
authors.initials: FM
authors.lastname: Diapouli
authors.forename: Gerard B
authors.initials: GB
authors.lastname: Nash
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
authors.forename: Steven M
authors.initials: SM
authors.lastname: Albelda
authors.forename: G Ed
authors.initials: GE
authors.lastname: Rainger
authors.forename: Paolo
authors.initials: P
authors.lastname: Meda
authors.forename: Beat A
authors.initials: BA
authors.lastname: Imhof
authors.forename: Sussan
authors.initials: S
authors.lastname: Nourshargh
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000276:immunology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D007136:Immunoglobulins / Q000276:immunology*; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018613:Microscopy, Confocal; D009504:Neutrophils / Q000276:immunology*; D015427:Reperfusion Injury / Q000276:immunology / Q000473:pathology; D057705:Transendothelial and Transepithelial Migration / Q000276:immunology*
chemical_list: D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C486723:Jam3 protein, mouse