Sitzung

53 - Freie Mitteilung
Inflammation & transplantation
16. Mai 2019, 10:15 - 11:45, Szenario 1, 5. OG

Abstract

2
Interactions between platelets and liver sinusoidal endothelial cells promote hepatic stellate cells to drive liver regeneration
A. Balaphas1, J. Meyer1, R. Perozzo1, P. Fontana1, S. Berndt2, A. Turzi2, P. Morel1, L. Scapozza1, K. Sadoul3, C. Gonelle-Gispert1, L. Bühler1, Presenter: A. Balaphas1 (1Geneva, 2Le Mont-sur-Lausanne, 3Grenoble/FR)

Ziel
Platelets and liver sinusoidal endothelial cells (LSEC) are implicated in liver regeneration. Our aim was to investigate the interactions between platelets and LSEC in liver regeneration through the study of the release of growth factors by LSEC and hepatic stellate cells (HSC).
Methoden
In vitro, freshly isolated pure mouse LSEC were co-incubated with resting platelets, activated platelets, or platelet releasates and secretion of various growth factors was measured with ELISA. To identify active components in platelet releasate, size exclusion chromatography was performed and resulting fractions were tested on LSEC for induction of growth factors secretion with ELISA. Conditioned culture medium of LSEC after exposure to platelets was added to primary HSC or hepatocytes and secretion of growth factors or cell proliferation was measured with ELISA and EdU assay. In vivo, platelets and LSEC interactions were analysed by confocal intravital microscopy after partial hepatectomy in mice.
Resultate
In vitro, co-incubation of resting platelets with LSEC resulted in a dose-dependent increase of interleukin-6 secretion (IL-6) by LSEC (IL-6: 75.4±6.6 pg/ml after incubation with 16 million platelets versus 2±1.1 pg/ml without platelets). The same effect was observed using activated platelets or releasate of activated platelets. Strikingly, IL-6 secretion was highest when high molecular weight fractions (> 80 kDa) of platelet releasate obtained by size exclusion chromatography were tested (IL-6 maximal: 1343±245.8 pg/ml versus control 8 ± 0.2 pg/ml, p<0.05). LSEC exposed to platelets did not increase proliferation of primary hepatocytes but stimulated HGF secretion by HSC (HGF: 574.1±124.5 pg/ml after stimulation versus 397±72.5 pg/ml without stimulation, p< 0.05). Following partial hepatectomy, adhesion of platelets to LSEC was significantly increased (55.2 ±2.1 % adherent platelets after partial hepatectomy versus 29.6±1.6% after sham surgery, p<0.05).
Schlussfolgerung
Our in vitro observations indicate that activated platelets release a component(s) of proteic nature inducing IL-6 secretion by LSEC, which in turn enhances release by HSC of HGF, the strongest mitogen for hepatocytes. Our in vivo data confirm that platelets adhere to LSEC shortly after liver injury.
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