Endothelial cells are damaged by autophagic induction before hepatocytes in Con A-induced acute hepatitis.
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.
Yang
Ming-Chen
MC
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan, Republic of China.
Chang
Chih-Peng
CP
Lei
Huan-Yao
HY
D000818:Animals; D001343:Autophagy; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology* / Q000503:physiopathology; D003208:Concanavalin A; D042783:Endothelial Cells / Q000276:immunology / Q000473:pathology*; D022781:Hepatocytes / Q000473:pathology*; D007371:Interferon-gamma / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D013997:Time Factors
D003208:Concanavalin A; D007371:Interferon-gamma