CX3CR1 and vascular adhesion protein-1-dependent recruitment of CD16+ monocytes across human liver sinusoidal endothelium
Open Access
- 12 February 2010
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hepatology
- Vol. 51 (6), 2030-2039
- https://doi.org/10.1002/hep.23591
Abstract
The liver contains macrophages and myeloid dendritic cells (mDCs) that are critical for the regulation of hepatic inflammation. Most hepatic macrophages and mDCs are derived from monocytes recruited from the blood through poorly understood interactions with hepatic sinusoidal endothelial cells (HSECs). Human CD16+ monocytes are thought to contain the precursor populations for tissue macrophages and mDCs. We report that CD16+ cells localize to areas of active inflammation and fibrosis in chronic inflammatory liver disease and that a unique combination of cell surface receptors promotes the transendothelial migration of CD16+ monocytes through human HSECs under physiological flow. CX3CR1 activation was the dominant pertussis-sensitive mechanism controlling transendothelial migration under flow, and expression of the CX3CR1 ligand CX3CL1 is increased on hepatic sinusoids in chronic inflammatory liver disease. Exposure of CD16+ monocytes to immobilized purified CX3CL1 triggered β1-integrin-mediated adhesion to vascular cell adhesion molecule-1 and induced the development of a migratory phenotype. Following transmigration or exposure to soluble CX3CL1, CD16+ monocytes rapidly but transiently lost expression of CX3CR1. Adhesion and transmigration across HSECs under flow was also dependent on vascular adhesion protein-1 (VAP-1) on the HSECs. Conclusion: Our data suggest that CD16+ monocytes are recruited by a combination of adhesive signals involving VAP-1 and CX3CR1 mediated integrin-activation. Thus a novel combination of surface molecules, including VAP-1 and CX3CL1 promotes the recruitment of CD16+ monocytes to the liver, allowing them to localize at sites of chronic inflammation and fibrosis. (Hepatology 2010)This publication has 60 references indexed in Scilit:
- Human Liver Dendritic Cells Promote T Cell HyporesponsivenessThe Journal of Immunology, 2009
- Lymphocyte recruitment to the liver: Molecular insights into the pathogenesis of liver injury and hepatitisToxicology, 2008
- Decrease of PECAM-1-gene-expression induced by proinflammatory cytokines IFN-γ and IFN-α is reversed by TGF-β in sinusoidal endothelial cells and hepatic mononuclear phagocytesBMC Physiology, 2008
- Leukocyte adhesion in the liver: Distinct adhesion paradigm from other organsJournal of Hepatology, 2008
- Kupffer cell heterogeneity: functional properties of bone marrow–derived and sessile hepatic macrophagesBlood, 2007
- Hepatitis C is associated with perturbation of intrahepatic myeloid and plasmacytoid dendritic cell functionJournal of Hepatology, 2007
- Expression of DC-SIGN and DC-SIGNR on Human Sinusoidal Endothelium: A Role for Capturing Hepatitis C Virus ParticlesThe American Journal of Pathology, 2006
- Intrasplenic steady-state dendritic cell precursors that are distinct from monocytesNature Immunology, 2006
- Monocyte and macrophage heterogeneityNature Reviews Immunology, 2005
- Identification of a novel anti‐integrin monoclonal antibody that recognises a ligand‐induced binding site epitope on the β1 subunitFEBS Letters, 1995