title: Caveolin-1 expression determines the route of neutrophil extravasation through skin microvasculature.
abstract: Interleukin-8 plays a key role in the acute inflammatory response by mediating recruitment of neutrophils through vessel walls into affected tissues. During this process, molecular signals guide circulating blood neutrophils to target specific vessels for extravasation and to migrate through such vessels via particular routes. Our results show that levels of endothelial caveolin-1, the protein responsible for the induction of the membrane domains known as caveolae, are critical to each of these processes. We demonstrate that, in response to the intradermal injection of interleukin-8, neutrophils are preferentially recruited to a unique subset of venules that express high levels of intercellular adhesion molecule-1 and low levels of caveolin-1. Our results show that neutrophils traverse human dermal microvascular endothelial cells using one of two pathways: a transcellular route directly through the cell or a paracellular route through cellular junctions. Caveolin-1 expression appears to favor the transcellular path while down-regulation of caveolin-1 promotes the paracellular route.
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Shana
authors.initials: S
authors.lastname: Marmon
authors.forename: Joseph
authors.initials: J
authors.lastname: Hinchey
authors.forename: Philmo
authors.initials: P
authors.lastname: Oh
authors.forename: Michael
authors.initials: M
authors.lastname: Cammer
authors.forename: Cecilia J
authors.initials: CJ
authors.lastname: de Almeida
authors.forename: Leslie
authors.initials: L
authors.lastname: Gunther
authors.forename: Cedric S
authors.initials: CS
authors.lastname: Raine
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000096:biosynthesis* / Q000235:genetics; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D055806:Microvessels / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D012867:Skin / Q000098:blood supply* / Q000276:immunology
chemical_list: D051242:Caveolin 1; D016209:Interleukin-8; D018799:Intercellular Adhesion Molecule-1