title: Pericytes support neutrophil subendothelial cell crawling and breaching of venular walls in vivo.
abstract: Neutrophil transmigration through venular walls that are composed of endothelial cells (ECs), pericytes, and the venular basement membrane is a key component of innate immunity. Through direct analysis of leukocyte-pericyte interactions in inflamed tissues using confocal intravital microscopy, we show how pericytes facilitate transmigration in vivo. After EC migration, neutrophils crawl along pericyte processes to gaps between adjacent pericytes in an ICAM-1-, Mac-1-, and LFA-1-dependent manner. These gaps were enlarged in inflamed tissues through pericyte shape change and were used as exit points by neutrophils in breaching the venular wall. The findings identify previously unknown roles for pericytes in neutrophil transmigration in vivo and add additional steps to the leukocyte adhesion cascade that supports leukocyte trafficking into sites of inflammation.
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
authors.forename: Doris
authors.initials: D
authors.lastname: Proebstl
authors.forename: Mathieu-Benoît
authors.initials: MB
authors.lastname: Voisin
authors.forename: Abigail
authors.initials: A
authors.lastname: Woodfin
authors.forename: James
authors.initials: J
authors.lastname: Whiteford
authors.forename: Fulvio
authors.initials: F
authors.lastname: D'Acquisto
authors.forename: Gareth E
authors.initials: GE
authors.lastname: Jones
authors.forename: David
authors.initials: D
authors.lastname: Rowe
authors.forename: Sussan
authors.initials: S
authors.lastname: Nourshargh
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000166:cytology; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism; D020286:Pericytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
chemical_list: D016207:Cytokines; C090509:Icam1 protein, mouse; D053583:Interleukin-1beta; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1