Kupffer cell production of cytokine-induced neutrophil chemoattractant following ischemia/reperfusion injury in rats.
We investigated the role of hepatic macrophages in the inflammatory response following reperfusion injury by blocking Kupffer cell phagocytosis with gadolinium chloride (GdCl3). Liver ischemia was induced in rats 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 untreated rats increased following reperfusion, peaked after 6 hours, and then gradually decreased. GdCl3 or heparin alone significantly decreased the serum levels of CINC (P < .05). In addition, pretreatment with GdCl3/heparin further inhibited the rise in the serum levels of CINC following reperfusion compared with those in untreated animals (P < .01). The in vitro production of CINC by Kupffer cells, obtained from animals pretreated with heparin or GdCl3, was significantly lower than that of cells isolated from untreated animals. Pretreatment with GdCl3/heparin 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 liver tissue peaked 3 hours after reperfusion in untreated animals. Pretreatment 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 neutrophils that accumulated in the liver 24 hours following reperfusion, compared with those in untreated animals. These results suggest that Kupffer cells release CINC and may play an important role in early neutrophil infiltration into the liver following ischemia/reperfusion.
Department of Surgery II, Kumamoto University Medical School, Japan.
N
N
Hisama
Y
Y
Yamaguchi
T
T
Ishiko
N
N
Miyanari
O
O
Ichiguchi
M
M
Goto
K
K
Mori
K
K
Watanabe
K
K
Kawamura
S
S
Tsurufuji
M
M
Ogawa
D000818:Animals; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000096:biosynthesis* / Q000235:genetics; D005682:Gadolinium / Q000494:pharmacology; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics; D006493:Heparin / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D007511:Ischemia / Q000378:metabolism*; D007728:Kupffer Cells / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism*
D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D006493:Heparin; D005682:Gadolinium; C038958:gadolinium chloride