Platelets Stimulate Liver Sinusoidal Endothelial Cells to Secrete Interleukin-6 During the Early Phase of Liver Regeneration in Mice.

J. Meyer,^1,2 E. Perroud,² P. Fontana,^3,4 K. Sadoul,⁵ P. Morel,^1,2 C. Gonelle-Gispert,² L. Bühler.^1,2

¹Division of Digestive and Transplantation Surgery, University Hospitals of Geneva, Geneva, Switzerland
²Unit of Surgical Research, University of Geneva, Geneva, Switzerland
³Division of Angiology and Haemostasis, University Hospitals of Geneva, Geneva, Switzerland
⁴Geneva Platelet Group, University of Geneva, Geneva, Switzerland
⁵Institute for Advanced Biosciences, Inserm U1209, Grenoble, France

Meeting: 2017 American Transplant Congress

Abstract number: C120

Keywords: Endothelial cells, Liver

Session Information

Session Name: Poster Session C: Innate Immunity

Session Type: Poster Session

Date: Monday, May 1, 2017

Session Time: 6:00pm-7:00pm

Presentation Time: 6:00pm-7:00pm

Location: Hall D1

Background and aims

Platelets and liver sinusoidal endothelial cells (LSEC) are known to both independently regulate liver regeneration. Our aim was to investigate the role of interactions between platelets and LSEC for liver regeneration.

Methods

Platelet and LSEC interactions were analyzed in vivo by intravital confocal microscopy in partially hepatectomized mice. Then, highly purified primary mouse LSEC or resident liver macrophages were co-incubated with increasing concentrations of resting platelet, activated platelets, or platelet releasates, and secretions of cytokines and growth factors were measured. Finally, IL-6 serum concentration was measured in mice with varying platelet counts after partial hepatectomy.

Results

Following partial hepatectomy in wild-type mice, in vivo adhesion of platelets to LSEC was significantly increased compared to sham-operated mice (55.19±2.14% versus 29.61±1.60%, p<0.05). Co-incubation of increasing numbers of resting or activated platelets with LSEC resulted in significantly enhanced IL-6 secretion by LSEC. IL-6 release by LSEC was highest after incubation with ADP-activated platelets when compared to thrombin-activated platelets. Thrombin activation or PAR4 modulation of platelets did not improve IL-6 secretion by LSEC compared to resting platelets. The effect of platelet releasates on LSEC was similar to whole platelets. IL-6 release by resident liver macrophages was present, but was not modulated by platelets. Decreased platelet counts led to decreased serum levels of IL-6 4h after partial hepatectomy in vivo (isotype control versus platelet-depleting antibody: 79.26±31.95 versus 13.60±6.37 [ng/ml], p<0.05).

Conclusion

Interactions between platelets and LSEC modulate IL-6 release by LSEC, but not by macrophages. After partial hepatectomy, platelets adhere to LSEC and serum IL-6 level depends on platelet concentration. These results indicate that platelets trigger LSEC to secrete cytokines relevant for liver regeneration.

CITATION INFORMATION: Meyer J, Perroud E, Fontana P, Sadoul K, Morel P, Gonelle-Gispert C, Bühler L. Platelets Stimulate Liver Sinusoidal Endothelial Cells to Secrete Interleukin-6 During the Early Phase of Liver Regeneration in Mice. Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Meyer J, Perroud E, Fontana P, Sadoul K, Morel P, Gonelle-Gispert C, Bühler L. Platelets Stimulate Liver Sinusoidal Endothelial Cells to Secrete Interleukin-6 During the Early Phase of Liver Regeneration in Mice. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/platelets-stimulate-liver-sinusoidal-endothelial-cells-to-secrete-interleukin-6-during-the-early-phase-of-liver-regeneration-in-mice/. Accessed November 22, 2024.

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