Lymphocyte traffic through sinusoidal endothelial cells is regulated by hepatocytes.
Crosstalk between hepatic sinusoidal ECs and closely juxtaposed hepatocytes via vascular endothelial growth factor is essential for the maintenance of sinusoidal endothelial growth and differentiation. We propose that paracrine interactions between endothelial cells and hepatocytes also may be responsible for the unique complement of adhesion receptors expressed on sinusoidal endothelium that regulate the recruitment of lymphocytes into the liver. To address this hypothesis, we developed an in vitro model of the hepatic sinusoid in which flowing lymphocytes could interact with hepatic endothelium conditioned by the presence of hepatocytes. Human hepatic sinusoidal endothelial cells cocultured with hepatocytes were activated so that they supported the adhesion of lymphocytes at levels equivalent to those seen on endothelium stimulated with the inflammatory cytokine tumour necrosis factor-beta. Lymphocyte adhesion was supported by intracellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin, with an additional contribution from the novel adhesion receptor VAP-1. In conclusion, we show that interactions between hepatocytes and endothelial cells amplify leukocyte recruitment through the sinusoids by regulating the expression and function of endothelial adhesion molecules. These paracrine interactions may be responsible for the induction of the adhesion molecules that support constitutive lymphocyte recruitment to the liver as well as contributing significantly to the patterns of leukocyte adhesion seen during episodes of hepatic inflammation.
Edwards
Sarah
S
Liver Research Group, Institute for Biomedical Science, Edgbaston, Birmingham, United Kingdom.
Lalor
Patricia F
PF
Nash
Gerard B
GB
Rainger
G Ed
GE
Adams
David H
DH
D006631:Amine Oxidase (Copper-Containing) / Q000032:analysis; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis; D002450:Cell Communication; D002465:Cell Movement; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000502:physiology*; D022781:Hepatocytes / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008214:Lymphocytes / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D015815:Cell Adhesion Molecules; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)