Hepatic sinusoidal endothelium avidly binds platelets in an integrin-dependent manner, leading to platelet and endothelial activation and leukocyte recruitment

Research output: Contribution to journalArticlepeer-review

Authors

Abstract

Platelets have recently been shown to drive liver injury in murine models of viral hepatitis and promote liver regeneration through the release of serotonin. Despite their emerging role in inflammatory liver disease, little is known about the mechanisms by which platelets bind to the hepatic vasculature. Therefore, we referenced public expression data to determine the profile of potential adhesive receptors expressed by hepatic endothelium. We then used a combination of tissue-binding and flow-based endothelial-binding adhesion assays to show that resting platelets bind to human hepatic sinusoidal endothelial cells and that the magnitude of adhesion is greatly enhanced by thrombin-induced platelet activation. Adhesion was mediated by the integrins Gp1b, αIIbβIII, and αvβ3, as well as immobilized fibrinogen. Platelet binding to hepatic endothelial cells resulted in NF-κB activation and increased chemokine secretion. The functional relevance of platelet binding was confirmed by experiments that showed markedly increased binding of neutrophils and lymphocytes to hepatic endothelial cells under shear conditions replicating those found in the hepatic sinusoid, which was in part dependent on P-selectin expression. Thus the ability of platelets to activate endothelium and promote leukocyte adhesion may reflect an additional mechanism through which they promote liver injury.

Details

Original languageEnglish
Pages (from-to)G469-78
JournalAmerican journal of physiology. Gastrointestinal and liver physiology
Volume304
Issue number5
Publication statusPublished - 1 Mar 2013

Keywords

  • NF-kappa B, Chemokines, Integrin alphaV, Chemokine CCL2, Humans, Platelet Activation, Endothelial Cells, Cell Adhesion Molecules, Antigens, CD31, Endothelium, Vascular, Neutrophil Infiltration, Blood Platelets, Antibodies, Blocking, Integrins, Cells, Cultured, Liver, Enzyme-Linked Immunosorbent Assay, von Willebrand Factor, Peptides, Interleukin-8, Gene Library