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Involvement of platelet‐activating factor in cytokine production and neutrophil activation after hepatic ischemia‐reperfusion
Author(s) -
Serizawa A,
Nakamura S,
Suzuki S,
Baba S,
Nakano M
Publication year - 1996
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510230649
Subject(s) - medicine , cytokine , platelet , platelet activating factor , ischemia , reperfusion injury , platelet activation , immunology
Although platelet‐activating factor (PAF) is implicated as an important mediator in the pathogenesis of hepatic ischemia‐reperfusion (IR) injury, the precise mechanism of its action has not been studied. We examined the hypothesis that PAF may influence neutrophils by promoting the production of tumor necrosis factor α (TNF‐α) and cytokine‐induced neutrophil chemoattractant (CINC), a member of the interleukin‐8 (IL‐8) family, and may be associated with liver and lung injury during the early phase of reperfusion after total hepatic ischemia. Rats pretreated with a specific PAF receptor antagonist exhibited suppression of the increase in plasma TNF‐α and CINC levels, as well as the priming of peripheral neutrophils for superoxide production after reperfusion when compared with animals pretreated with physiological saline. These effects resulted in a reduction of plasma liver enzymes and of hepatic and pulmonary neutrophil sequestration, as well as an increased survival rate. There was a strong correlation between the time course of CINC release and hepatic or pulmonary neutrophil sequestration. We concluded that PAF activates neutrophils, either directly or by promoting the production of TNF‐α and CINC, and is involved in hepatic IR injury.