KUPFFER CELL PRODUCTION OF CYTOKINE-INDUCED NEUTROPHIL CHEMOATTRACTANT FOLLOWING ISCHEMIA REPERFUSION INJURY IN RATS/

We investigated the role of hepatic macrophages in the inflammatory re sponse following reperfusion injury by blocking Kupffer cell phagocyto sis with gadolinium chloride (GdCl3). Liver ischemia was induced in ra ts by occluding the portal vein for 30 minutes. A bolus of GdCl3 (7 mg /kg) was injected intravenously 1 and 2 days before surgery. The serum levels of cytokine-induced neutrophil chemoattractant (CINC) in untre ated rats increased following reperfusion, peaked after 6 hours, and t hen gradually decreased, GdCl3 or heparin alone significantly decrease d the serum levels of CINC (P < .05). In addition, pretreatment with G dCl3/heparin further inhibited the rise in the serum levels of CINC fo llowing reperfusion compared with those in untreated animals (P < .01) . The in vitro production of CINC by Kupffer cells, obtained from anim als pretreated with heparin or GdCl3, was significantly lower than tha t of cells isolated from untreated animals. Pretreatment with GdCl3/he parin further decreased CINC production by Kupffer cells compared with that of cells from animals that were pretreated with heparin or GdCl3 alone. The expression of CINC transcripts in Kupffer cells or in live r tissue peaked 3 hours after reperfusion in untreated animals. Pretre atment with heparin, GdCl3, or both significantly decreased the levels of CINC messenger RNA (mRNA) transcripts, Pretreatment with heparin, GdCl3, or GdCl3/heparin significantly decreased the number of neutroph ils that accumulated in the liver 24 hours following reperfusion, comp ared with those in untreated animals. These results suggest that Kupff er cells release CINC and may play an important role in early neutroph il infiltration into the liver following ischemia/reperfusion.