Participation of platelet-activating factor in the lipopolysaccharide-induced liver injury in partially hepatectomized rats

Platelet-activating factor (PAF) has been shown to be an important mediator in the pathogenesis of lipopolysaccharide (LPS)-induced liver injury in re generating rat livers. Both LPS and PAF activate nuclear factor-kappa B (NF -kappa B), a key transcription factor for tumor necrosis factor-alpha (TNF- alpha) and cytokine-induced neutrophil chemoattractant (CINC). The aim of t his study is to investigate how PAF participates in the LPS-induced and NF- kappa B-mediated regulation of TNF-alpha and CINC in regenerating rat liver s, LPS (1.5 mg/kg) was intravenously administered into 70% hepatectomized r ats and sham-operated rats 48 hours postoperatively, LPS administration cau sed a high mortality rate, scattered necrosis in the liver with infiltratio n of CINC-positive neutrophils, and a continuous CINC messenger RNA up-regu lation and activation of NF-kappa B in the liver only in hepatectomized rat s. These phenomena were all effectively prevented by pretreatment and postt reatment with a PAF receptor antagonist, TCV-309. Hepatectomized rats showe d NF-kappa B staining in hepatocytes, Kupffer cells, and neutrophils around necrosis 4 hours after the LPS injection, representing the activation of t his factor in these cells. Based on these results, we propose that PAF cont ributes to continuous CINC up-regulation and NF-kappa B activation via accu mulation and activation of neutrophils, and thereby is involved in LPS-indu ced liver injury in regenerating rat livers.