Increased neutrophil function induced by bile duct ligation in a rat model

✍ Scribed by Rachel Levy; Francisc Schlaeffer; Arie Keynan; Ofra Nagauker; Arie Yaari; Emanuel Sikuler

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 718 KB
• Volume: 17
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840170522

✦ Synopsis

Neutrophil function was studied in rats with common bile duct ligation. Superoxide production stimulated by phorbol myristate acetate, opsonized zymosan or formyl-methionyl-leucyl-phenylalanine; phagocytosis; and chemotaxis were significantly greater in neutrophils from rats with common bile duct ligation than in sham-operated control rats, Enhanced neutrophil activity was observed within 12 hr of bile duct ligation; it remained increased during the 15-day study. Preincubation of neutrophils from control rats with sera of rats with common bile duct ligation did not increase superoxide generation. This suggests that the high superoxide production observed in neutrophils of rats with common bile duct ligation was not an immediate effect of the serum. Neutrophils of rats with portal vein ligation exhibited normal activity, indicating that portal systemic shuntingper se is not the underlying mechanism for increased activity. The elevated levels of AST and alkaline phosphatase, indicating liver damage, that appeared within 12 hr of bile duct ligation correlated with the increased superoxide generation. (HEPATOLOGY 1993;17:908-914.)

Chemotaxis, phagocytosis and superoxide generation are the mechanisms of killing invasive microbial pathogens by polymorphonuclear cells (PMNs) and macrophages (1, 2). Administration of several different hepatotoxinsincluding CCl,, acetaminophen and lipopolysaccharide -to animal models has been associated with activation of Kupffer cells and accumulation of inflammatory macrophages in the liver (3-5). Macrophages from such animals exhibit enhanced phagocytic chemotactic and metabolic activity and increased release of superoxides and interleukins (6-10). In addition, it has recently been shown that neutrophils are activated and accumulate in the liver during the early stages of endotoxemia in rats (4, 11) and after ischemia-reperfusion damage to rat liver (12).