title: Venular basement membranes contain specific matrix protein low expression regions that act as exit points for emigrating neutrophils.
abstract: The mechanism of leukocyte migration through venular walls in vivo is largely unknown. By using immunofluorescence staining and confocal microscopy, the present study demonstrates the existence of regions within the walls of unstimulated murine cremasteric venules where expression of key vascular basement membrane (BM) constituents, laminin 10, collagen IV, and nidogen-2 (but not perlecan) are considerably lower (<60%) than the average expression detected in the same vessel. These sites were closely associated with gaps between pericytes and were preferentially used by migrating neutrophils during their passage through cytokine-stimulated venules. Although neutrophil transmigration did not alter the number/unit area of extracellular matrix protein low expression sites, the size of these regions was enlarged and their protein content was reduced in interleukin-1beta-stimulated venules. These effects were entirely dependent on the presence of neutrophils and appeared to involve neutrophil-derived serine proteases. Furthermore, evidence was obtained indicating that transmigrating neutrophils carry laminins on their cell surface in vivo. Collectively, through identification of regions of low extracellular matrix protein localization that define the preferred route for transmigrating neutrophils, we have identified a plausible mechanism by which neutrophils penetrate the vascular BM without causing a gross disruption to its intricate structure.
authors.affiliation: Cardiovascular Medicine Unit, National Heart and Lung Institute, Division of Medicine, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London W12 ONN, England, UK.
authors.forename: Shijun
authors.initials: S
authors.lastname: Wang
authors.forename: Mathieu-Benoit
authors.initials: MB
authors.lastname: Voisin
authors.forename: Karen Y
authors.initials: KY
authors.lastname: Larbi
authors.forename: John
authors.initials: J
authors.lastname: Dangerfield
authors.forename: Christoph
authors.initials: C
authors.lastname: Scheiermann
authors.forename: Maxine
authors.initials: M
authors.lastname: Tran
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Maxwell
authors.forename: Lydia
authors.initials: L
authors.lastname: Sorokin
authors.forename: Sussan
authors.initials: S
authors.lastname: Nourshargh
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000502:physiology*; D002465:Cell Movement; D017931:DNA Primers; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D007962:Leukocytes / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply; D009504:Neutrophils / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014699:Venules / Q000502:physiology*
chemical_list: D017931:DNA Primers; D016326:Extracellular Matrix Proteins