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Publication : Endothelial cells are damaged by autophagic induction before hepatocytes in Con A-induced acute hepatitis.

First Author  Yang MC Year  2010
Journal  Int Immunol Volume  22
Issue  8 Pages  661-70
PubMed ID  20547544 Mgi Jnum  J:162090
Mgi Id  MGI:4462737 Doi  10.1093/intimm/dxq050
Citation  Yang MC, et al. (2010) Endothelial cells are damaged by autophagic induction before hepatocytes in Con A-induced acute hepatitis. Int Immunol 22(8):661-70
abstractText  We have reported both T-cell-dependent and -independent hepatitis in immunocompetent and immunodeficiency mice, respectively, after intravenous injection of Con A in mice. The mode of hepatocyte cell death is different: autophagy for T-cell-independent hepatitis in contrast to apoptosis for T-cell-dependent one. In this study, we further demonstrate that liver blood vessels are the first target in both modes. The infused Con A bond to the hepatic vascular endothelial cells and cause its damage with autophagy. Before the elevation of the serum alanine aminotransferase at 6 h post-injection, the plasma leakage and hemorrhage occur at 1-3 h without inflammation. Con A induces autophagy of endothelial cells and hemorrhage that is enhanced by IFN-gamma. Using the endothelial cell line HMEC-1, a dose- and time-dependent cell death with autophagic LC3-II (microtubule-associated protein light chain 3) conversion was induced by Con A and was enhanced by IFN-gamma. In conclusion, Con A induced autophagy on hepatic endothelial cells; the damage of liver blood vessel occurs before the induction of T-cell-dependent hepatitis via apoptosis or T-cell-independent hepatitis via autophagy.
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