Infiltrating polymorphonuclear leukocytes and apoptotic bodies derived from hepatocytes but not from ballooning hepatocytes containing Mallory bodies show nuclear DNA fragmentation in alcoholic hepatitis.
BACKGROUND
The mechanism of liver cell death in alcoholic hepatitis is still controversial. There is evidence that polymorphonuclear leukocytes (PMNs) which infiltrate liver parenchyma are involved in liver cell death.


METHODS
We employed terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick end labeling (TUNEL) method to determine the cells that underwent apoptosis in liver specimens obtained from 1 normal liver, 23 livers with nonalcoholic liver disease, and 11 livers with alcoholic liver diseases (4 alcoholic hepatic fibrosis, 4 alcoholic hepatitis, and 3 alcoholic cirrhosis). The Fas, bcl-2, and CD15 antigens were immunolocalized to analyze the relationship between these antigens and apoptosis.


RESULTS
Few TUNEL-positive reactions were found in normal liver. Apoptotic bodies in acute and chronic viral hepatitis were found to be TUNEL-positive. TUNEL-positive materials were also abundant in the cytoplasm of macrophages at the area of parenchymal collapse in viral liver diseases. Mononuclear cells that infiltrated liver parenchyma and portal tracts occasionally showed TUNEL-positive reactions, which reflected the activation-induced apoptosis of T lymphocytes. In alcoholic liver diseases, the incidence of apoptotic bodies derived from hepatocytes varied from 0 to 1.00/mm2. In addition, a considerable portion (0.2-16.5%) of infiltrating PMNs in alcoholic hepatitis were TUNEL-positive. In contrast, the nuclei of ballooning hepatocytes that contained Mallory bodies revealed few positive TUNEL reactions. Interestingly, the density of CD15-positive PMNs was well correlated with peripheral white blood cell counts (r = 0.842, p < 0.005).


CONCLUSIONS
PMNs that infiltrate liver parenchyma show an activation-induced cell death-like phenomenon in alcoholic hepatitis, like activated T cells that infiltrate in viral hepatitis. This apoptosis phenomenon may follow the degranulation of PMNs, which may cause a necrosis of ballooning hepatocytes that contain Mallory bodies through satellitosis.
Takahashi
T
T
Third Department of Internal Medicine, Niigata University School of Medicine, Niigata, Japan. torutoru@med.niigata-u.ac.jp
So-Wan
T
T
Kamimura
T
T
Asakura
H
H
D017209:Apoptosis; D053938:DNA Fragmentation; D006519:Hepatitis, Alcoholic / Q000473:pathology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D002479:Inclusion Bodies / Q000473:pathology*; D008099:Liver / Q000473:pathology*; D008104:Liver Cirrhosis, Alcoholic / Q000473:pathology; D009504:Neutrophils / Q000473:pathology*