Immunohistochemical study of hyaluronate receptor (CD44) in alcoholic liver disease.
BACKGROUND
It has been suggested that the elevation of serum hyaluronate (HA) levels in liver diseases may be due to increased synthesis of HA by hepatic stellate cells or decreased degradation by sinusoidal endothelial cells. The increase in serum HA levels in patients with cirrhosis is thought to be a response to a reduction in HA receptors (CD44) in hepatic sinusoidal endothelial cells. To learn more about how alcohol affects the number and distribution of HA receptors of hepatic sinusoidal endothelial cells, we immunohistochemically studied CD44 levels in liver biopsy obtained from patients with alcoholic liver disease (ALD patients) and also from patients with nonalcoholic liver disease (non-ALD); ALD patients were evaluated when they were currently drinking and again after they became abstinent. Normal liver tissue obtained from three autopsy cases served as a control.


METHODS
Liver biopsy specimens were obtained from 18 ALD patients and 12 non-ALD patients. In ALD patients, liver biopsy was performed twice within 3 days and 4 to 8 weeks after abstinence when serum levels of aspartate aminotransferase and alanine aminotransferase became normal. CD44 in liver specimens was stained with anti-CD44 antibody by streptavidine-biotin-peroxidase complex. The intensity of the staining of CD44 in liver tissue was determined by a computer-assisted imaging analyzer. We also measured serum levels of CD44 in both ALD and non-ALD patients.


RESULTS
The intensity and the number of CD44 staining increased in both ALD and non-ALD patients compared with those in normal liver, which was negative. The staining intensity of CD44 in liver specimens obtained from patients with ALD who were active in alcohol consumption were significantly higher when compared with patients with ALD after abstinence. Serum levels of CD44 in patients with liver disease increased compared with those of healthy subjects.


CONCLUSIONS
The results suggest that HA receptors may increase to degrade the increased HA in serum and/or liver.
Urashima
S
S
Department of Internal Medicine, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
Tsutsumi
M
M
Ozaki
K
K
Tsuchishima
M
M
Shimanaka
K
K
Ueshima
Y
Y
Takase
S
S
D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001706:Biopsy; D000431:Ethanol / Q000008:administration & dosage; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis*; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry*; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged
D018960:Hyaluronan Receptors; D000431:Ethanol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase