title: Human liver sinusoidal endothelial cells promote intracellular crawling of lymphocytes during recruitment: A new step in migration.
abstract: The recruitment of lymphocytes via the hepatic sinusoidal channels and positioning within liver tissue is a critical event in the development and persistence of chronic inflammatory liver diseases. The hepatic sinusoid is a unique vascular bed lined by hepatic sinusoidal endothelial cells (HSECs), a functionally and phenotypically distinct subpopulation of endothelial cells. Using flow-based adhesion assays to study the migration of lymphocytes across primary human HSECs, we found that lymphocytes enter into HSECs, confirmed by electron microscopy demonstrating clear intracellular localization of lymphocytes in vitro and by studies in human liver tissues. Stimulation by interferon-γ increased intracellular localization of lymphocytes within HSECs. Furthermore, using confocal imaging and time-lapse recordings, we demonstrated "intracellular crawling" of lymphocytes entering into one endothelial cell from another. This required the expression of intracellular adhesion molecule-1 and stabilin-1 and was facilitated by the junctional complexes between HSECs.
  
  
  
  Lymphocyte migration is facilitated by the unique structure of HSECs. Intracellular crawling may contribute to optimal lymphocyte positioning in liver tissue during chronic hepatitis. (Hepatology 2017;65:294-309).
authors: National Institute for Health Research Birmingham Liver Biomedical Research Unit and Centre for Liver Research, Medical School, University of Birmingham, Birmingham, United Kingdom.
authors: Daniel A
authors: DA
authors: Patten
authors: National Heart and Lung Institute, Imperial Centre for Translational and Experimental Medicine, Imperial College London, London, United Kingdom.
authors: Garrick K
authors: GK
authors: Wilson
authors: Institute of Immunology and Immunotherapy, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom.
authors: Dalan
authors: D
authors: Bailey
authors: Technology Hub Imaging Facility, Infrastructure and Facilities, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors: Robert K
authors: RK
authors: Shaw
authors: MediCity Research Laboratory, and Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
authors: Sirpa
authors: S
authors: Jalkanen
authors: MediCity Research Laboratory, and Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
authors: Marko
authors: M
authors: Salmi
authors: Centre for Immunology and Infection, Department of Biology, University of York, York, United Kingdom.
authors: Antal
authors: A
authors: Rot
authors: National Institute for Health Research Birmingham Liver Biomedical Research Unit and Centre for Liver Research, Medical School, University of Birmingham, Birmingham, United Kingdom.
authors: Chris J
authors: CJ
authors: Weston
authors: National Institute for Health Research Birmingham Liver Biomedical Research Unit and Centre for Liver Research, Medical School, University of Birmingham, Birmingham, United Kingdom.
authors: David H
authors: DH
authors: Adams
authors: National Institute for Health Research Birmingham Liver Biomedical Research Unit and Centre for Liver Research, Medical School, University of Birmingham, Birmingham, United Kingdom.
authors: Shishir
authors: S
authors: Shetty
mesh_terms: D002196:Capillaries / Q000166:cytology*; D002465:Cell Movement; D003593:Cytoplasm; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D008099:Liver / Q000098:blood supply; D008214:Lymphocytes / Q000502:physiology*