Platelets prevent acute hepatitis induced by anti‐fas antibody

• DOI: 10.1111/j.1440-1746.2010.06334.x
• Publication Date: 2010-03-31T09:43:01Z
• Authors: Katsuji Hisakura; Soichiro Murata; Kazuhiro Takahashi; Ryota Matsuo; Sugiru Pak; Naoya Ikeda; Takuya Kawasaki; Keisuke Kohno; Andriy Myronovych; Yoritaka Nakano; Osamu Ikeda; Motonobu Watanabe; Nobuhiro Ohkohchi
• Keywords: Male; 0301 basic medicine; Platelet Count; Endothelial Cells; Alanine Transaminase; Apoptosis; Staurosporine; Antibodies; Recombinant Proteins; 3. Good health; Cell Line; Hepatitis; Polyethylene Glycols; Mice, Inbred C57BL; Disease Models, Animal; Mice; Necrosis; 03 medical and health sciences; Acute Disease; Hepatocytes; In Situ Nick-End Labeling; Animals; Apoptosis Regulatory Proteins

AbstractBackground and Aim: Platelets provide many functions in the body, especially to the liver. The purpose of this study is to investigate the effect of thrombocytosis with acute hepatitis induced by anti‐Fas antibody and its mechanism.Methods: Acute hepatitis was induced by administration of anti‐Fas antibody in normal and thrombocytotic C57BL6J mice. For thrombocytosis, thrombopoietin; PEG‐rHuMGDF was injected 5 days before and just prior to administration of anti‐Fas antibody. To investigate the mechanisms, hepatocyte cell line (AML12) and sinusoidal endothelial cell line (M1) were induced apoptosis by staurosporine. They were cultured with platelets or thrombopoietin. Examination items were as follows: platelet number, alanine aminotransferase (ALT), histological findings, TUNEL (TdT‐mediated dUTP‐biotin Nick End Labeling) staining, and the expression of proteins associated with apoptosis in vivo and in vitro.Results: Platelets were significantly increased in the thrombocytotic group (P < 0.01). Serum ALT levels were significantly reduced by thrombocytosis at 6, 24 and 72 h after the administration (P < 0.05). In histological findings, hemorrhagic necrosis was observed in the normal group, but not observed in the thrombocytotic group. TUNEL‐positive hepatocytes were reduced and the expression of cleaved caspase‐3 was significantly decreased in the thrombocytotic group. The phosphorylation of Akt, the increment of Bcl‐xL and the decrease of cleaved caspase‐3 were observed in AML12 cells cultured with platelets, but were not observed cultured with thrombopoietin. Platelets and thrombopoietin had no anti‐apoptotic effect on M1 cells.Conclusion: Increase of platelets has a preventative effect against acute hepatitis induced by the anti‐Fas antibody. It is suggested that platelets have a direct protective effect against apoptosis of hepatocytes.