A novel role of alkaline phosphatase in protection from immunological liver injury in mice.
OBJECTIVE
Little is known about the role of alkaline phosphatase (AP) in liver diseases, except for its elevation in jaundice or cholestasis. Its substrate, endotoxin, is usually elevated in patients as well as animals with liver damage. This study aimed to provide evidence for its new role as protection against immunological liver damage.


METHODS
Liver injury was induced in mice by delayed-type hypersensitivity to picryl chloride. AP activity was measured using a commercial kit.


RESULTS
In acute liver injury, a significant decrease in AP activity in serum was observed but there was an increase in liver tissue. Single administration of cyclophosphamide before sensitization with picryl chloride exacerbated the liver injury, with more serious AP changes, while consecutive use after the sensitization alleviated the injury with a recovery from the changes. When liver injury proceeded for 1 week, both serum and liver showed decreased AP activity. Lipopolysaccharide facilitated alanine transaminase release from levamisole-pretreated but not non-treated hepatocytes from naive mice. However, the release was confirmed from liver slices of mice with liver injury proceeding for 1 week, even without levamisole pretreatment.


CONCLUSIONS
The development of liver injury may lead to a dysfunction in AP synthesis and release. Levamisole may make normal hepatocytes, like the hepatocytes from liver-injured mice, highly sensitive to lipopolysaccharide through inhibiting AP synthesis. The findings obtained in this study suggest that AP may contribute to protection from injury by a mechanism involving neutralization of endotoxin.
Xu
Qiang
Q
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, China. qiangxu@jlonline.com
Lu
Zhaohua
Z
Zhang
Xianming
X
D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control*; D003520:Cyclophosphamide / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control*; D007978:Levamisole / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D051379:Mice; D008813:Mice, Inbred ICR; D010853:Picryl Chloride / Q000633:toxicity
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D007978:Levamisole; D003520:Cyclophosphamide; D000469:Alkaline Phosphatase; D010853:Picryl Chloride