Human Monocytes - CD14, CD16 - Ziegler-Heitbrock

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CX3CR1 and VAP-1 dependent recruitment of CD16+ monocytes across human liver sinusoidal endothelium

Abstract

Background: The liver contains macrophages and myeloid dendritic cells (mDC) that are critical for the regulation of hepatic inflammation. Most hepatic macrophages and mDC are derived from monocytes recruited from blood via poorly understood interactions with hepatic sinusoidal endothelial cells (HSEC). Human CD16+ monocytes are believed to contain the precursor populations for tissue macrophages and mDC. Results: 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 HSEC 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 1 integrin-mediated adhesion to VCAM-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 HSEC under flow was also dependent on vascular adhesion protein-1 (VAP-1) on the HSEC. Conclusions: 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.)

Authors: Alexander I. Aspinall, Stuart M. Curbishley, Patricia F. Lalor, Chris J. Weston, Miroslava Blahova, Evaggelia Liaskou, Rebecca M Adams, Andrew P. Holt, David H. Adams
Journal: Hepatology. 51: 2030-2039
Year: 2010
PubMed: Find in PubMed