Kupffer cell-depleted rats have a diminished acute-phase response following major liver resection.
Partial hepatectomy (PH)-induced Kupffer cell (KC) activation results in a rapid release of cytokines inducing the acute-phase response (APR). This study was done to evaluate the role of Kupffer cells (KCs) in the course of the APR following PH and a consecutive endotoxin challenge. KC depletion was performed in rats by i.v. administration of 1 mL liposome-encapsulated dichloromethylene diphosohonate (Cl2MDP). Control rats received 1 mL NaCl 0.9%. Forty-eight hours later, PH was performed. At 24 h after PH, rats were randomized to receive either 1 mL NaCl 0.9% (saline) or 50 microg/kg LPS i.v. in 1 mL. Animals were sacrificed at 4 h after LPS or saline infusion. The APR was determined by measuring hepatic gene expression of alpha 2-macroglobulin, alpha 1-acid glycoprotein, and IL-6 and expression of hepatic albumin. The APR was significantly depressed in KC-depleted rats. Despite increased IL-6 mRNA synthesis in response to low-dose LPS, no enhancement of acute-phase protein synthesis (APP) was found in KC-depleted rats. Hepatic failure was most profound in KC-depleted rats, as indicated by elevated plasma levels of liver transaminases and ammonia. We conclude that after PH, KC function in the remnant liver is important for the acute-phase reaction and reduces endotoxin-induced hepatocyte damage.
Prins
Hubert A
HA
Department of Surgery, VU University Medical Centre, Amsterdam, The Netherlands.
Meijer
Catharina
C
Boelens
Petra G
PG
Diks
Jeroen
J
Holtz
Rogier
R
Masson
Sylvie
S
Daveau
Maryvonne
M
Meijer
Sybren
S
Scotté
Michel
M
van Leeuwen
Paul A M
PA
D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D000210:Acute-Phase Reaction / Q000473:pathology*; D000418:Albumins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004002:Clodronic Acid / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000008:administration & dosage / Q000633:toxicity; D006498:Hepatectomy / Q000379:methods; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects / Q000502:physiology*; D008099:Liver / Q000473:pathology* / Q000601:surgery*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D009961:Orosomucoid / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011183:Postoperative Complications / Q000473:pathology; D000644:Quaternary Ammonium Compounds / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013530:Surgical Wound Infection / Q000473:pathology; D000511:alpha-Macroglobulins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D000209:Acute-Phase Proteins; D000418:Albumins; D004731:Endotoxins; D015850:Interleukin-6; D009961:Orosomucoid; D000644:Quaternary Ammonium Compounds; D000511:alpha-Macroglobulins; D004002:Clodronic Acid; D001219:Aspartate Aminotransferases