Semin Thromb Hemost 2010; 36(2): 170-174
DOI: 10.1055/s-0030-1251501
© Thieme Medical Publishers

The Role of Platelets in Liver Inflammation and Regeneration

Ton Lisman1 , Robert J. Porte1
  • 1Department of Surgery, Section Hepatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Further Information

Publication History

Publication Date:
22 April 2010 (online)

ABSTRACT

Platelets play a pivotal role in thrombosis and hemostasis, but an increasing variety of extra-hemostatic functions of platelets are being recognized. This review summarizes recent advances in the understanding of the role of platelets in various pathologies involving the liver. In ischemia/reperfusion injury of the liver, platelets appear to play a dual role. On one hand, platelets bind to the activated sinusoidal endothelium and induce apoptosis of these cells; on the other hand, platelet-derived serotonin assists in repair of the ischemic tissue. Furthermore, platelets are attracted to the liver following systemic inflammatory stimuli, but the significance of this finding is still unclear. Platelets and platelet-derived serotonin appear vital for liver regeneration following a partial liver resection. Finally, platelets and platelet-derived serotonin aggravate viral hepatitis by affecting the microcirculation in the liver.

REFERENCES

  • 1 Wagner D D, Burger P C. Platelets in inflammation and thrombosis.  Arterioscler Thromb Vasc Biol. 2003;  23(12) 2131-2137
  • 2 Nurden A T, Nurden P, Sanchez M, Andia I, Anitua E. Platelets and wound healing.  Front Biosci. 2008;  13 3532-3548
  • 3 Borsig L. The role of platelet activation in tumor metastasis.  Expert Rev Anticancer Ther. 2008;  8(8) 1247-1255
  • 4 Italiano Jr J E, Richardson J L, Patel-Hett S et al.. Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet alpha granules and differentially released.  Blood. 2008;  111(3) 1227-1233
  • 5 Langer H F, Gawaz M. Platelets in regenerative medicine.  Basic Res Cardiol. 2008;  103(4) 299-307
  • 6 Lev E I, Estrov Z, Aboulfatova K et al.. Potential role of activated platelets in homing of human endothelial progenitor cells to subendothelial matrix.  Thromb Haemost. 2006;  96(4) 498-504
  • 7 Diacovo T G, Roth S J, Buccola J M, Bainton D F, Springer T A. Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the beta 2-integrin CD11b/CD18.  Blood. 1996;  88(1) 146-157
  • 8 Blair P, Flaumenhaft R. Platelet alpha-granules: basic biology and clinical correlates.  Blood Rev. 2009;  23(4) 177-189
  • 9 Zimmerman G A, Weyrich A S. Signal-dependent protein synthesis by activated platelets: new pathways to altered phenotype and function.  Arterioscler Thromb Vasc Biol. 2008;  28(3) s17-s24
  • 10 Witters P, Freson K, Verslype C et al.. Review article: blood platelet number and function in chronic liver disease and cirrhosis.  Aliment Pharmacol Ther. 2008;  27(11) 1017-1029
  • 11 Goulis J, Chau T N, Jordan S et al.. Thrombopoietin concentrations are low in patients with cirrhosis and thrombocytopenia and are restored after orthotopic liver transplantation.  Gut. 1999;  44(5) 754-758
  • 12 Hugenholtz G G, Porte R J, Lisman T. The platelet and platelet function testing in liver disease.  Clin Liver Dis. 2009;  13(1) 11-20
  • 13 Lisman T, Bongers T N, Adelmeijer J et al.. Elevated levels of von Willebrand factor in cirrhosis support platelet adhesion despite reduced functional capacity.  Hepatology. 2006;  44(1) 53-61
  • 14 Cywes R, Packham M A, Tietze L et al.. Role of platelets in hepatic allograft preservation injury in the rat.  Hepatology. 1993;  18(3) 635-647
  • 15 Sindram D, Porte R J, Hoffman M R, Bentley R C, Clavien P A. Platelets induce sinusoidal endothelial cell apoptosis upon reperfusion of the cold ischemic rat liver.  Gastroenterology. 2000;  118(1) 183-191
  • 16 Khandoga A, Biberthaler P, Enders G et al.. P-selectin mediates platelet-endothelial cell interactions and reperfusion injury in the mouse liver in vivo.  Shock. 2002;  18(6) 529-535
  • 17 Yadav S S, Howell D N, Steeber D A, Harland R C, Tedder T F, Clavien P A. P-Selectin mediates reperfusion injury through neutrophil and platelet sequestration in the warm ischemic mouse liver.  Hepatology. 1999;  29(5) 1494-1502
  • 18 Cywes R, Mullen J B, Stratis M A et al.. Prediction of the outcome of transplantation in man by platelet adherence in donor liver allografts. Evidence of the importance of prepreservation injury.  Transplantation. 1993;  56(2) 316-323
  • 19 Sindram D, Porte R J, Hoffman M R, Bentley R C, Clavien P A. Platelets induce sinusoidal endothelial cell apoptosis upon reperfusion of the cold ischemic rat liver.  Gastroenterology. 2000;  118(1) 183-191
  • 20 Sindram D, Porte R J, Hoffman M R, Bentley R C, Clavien P A. Synergism between platelets and leukocytes in inducing endothelial cell apoptosis in the cold ischemic rat liver: a Kupffer cell-mediated injury.  FASEB J. 2001;  15(7) 1230-1232
  • 21 Nocito A, Georgiev P, Dahm F et al.. Platelets and platelet-derived serotonin promote tissue repair after normothermic hepatic ischemia in mice.  Hepatology. 2007;  45(2) 369-376
  • 22 Nakamura M, Shibazaki M, Nitta Y, Endo Y. Translocation of platelets into Disse spaces and their entry into hepatocytes in response to lipopolysaccharides, interleukin-1 and tumour necrosis factor: the role of Kupffer cells.  J Hepatol. 1998;  28(6) 991-999
  • 23 Endo Y, Nakamura M. The effect of lipopolysaccharide, interleukin-1 and tumour necrosis factor on the hepatic accumulation of 5-hydroxytryptamine and platelets in the mouse.  Br J Pharmacol. 1992;  105(3) 613-619
  • 24 Clavien P A. Liver regeneration: a spotlight on the novel role of platelets and serotonin.  Swiss Med Wkly. 2008;  138(25-26) 361-370
  • 25 Lesurtel M, Graf R, Aleil B et al.. Platelet-derived serotonin mediates liver regeneration.  Science. 2006;  312(5770) 104-107
  • 26 Murata S, Hashimoto I, Nakano Y, Myronovych A, Watanabe M, Ohkohchi N. Single administration of thrombopoietin prevents progression of liver fibrosis and promotes liver regeneration after partial hepatectomy in cirrhotic rats.  Ann Surg. 2008;  248(5) 821-828
  • 27 Murata S, Ohkohchi N, Matsuo R, Ikeda O, Myronovych A, Hoshi R. Platelets promote liver regeneration in early period after hepatectomy in mice.  World J Surg. 2007;  31(4) 808-816
  • 28 Alkozai E M, Nijsten M, de Jong K P et al.. Immediate postoperative low platelet count is associated with delayed liver function recovery after partial liver resection.  Ann Surg. 2010;  251(2) 300-306
  • 29 Lesurtel M, Graf R, Aleil B et al.. Platelet-derived serotonin mediates liver regeneration.  Science. 2006;  312(5770) 104-107
  • 30 Matondo R B, Punt C, Homberg J et al.. Deletion of the serotonin transporter in rats disturbs serotonin homeostasis without impairing liver regeneration.  Am J Physiol Gastrointest Liver Physiol. 2009;  296(4) G963-G968
  • 31 Iannacone M, Sitia G, Isogawa M et al.. Platelets mediate cytotoxic T lymphocyte-induced liver damage.  Nat Med. 2005;  11(11) 1167-1169
  • 32 Lang P A, Contaldo C, Georgiev P et al.. Aggravation of viral hepatitis by platelet-derived serotonin.  Nat Med. 2008;  14(7) 756-761

Ton LismanPh.D. 

Department of Surgery, Surgical Research Laboratory, University Medical Center Groningen

BA44, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands

Email: j.a.lisman@chir.umcg.nl

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