The role of Kupffer cells after major liver surgery.
BACKGROUND
Kupffer cells (KCs) are the resident macrophages of the liver. KCs have an enormous endotoxin eliminating capacity. Endotoxins play an important role in the development of systemic complications after partial hepatectomy by activating KCs. The role of KCs and endotoxins after partial hepatectomy is investigated.


METHODS
Wistar rats (n = 16, 250-275 g) were randomly assigned to have 1 mL dichloromethylene-diphosphonate (CL2MDP) or 1 mL NaCl 0.9% i.v. Forty-eight hours later, all rats received a two-thirds liver resection. Twenty-four hours later, rats received at random 50 microg/kg endotoxin (LPS) in 1 mL or 1 mL of NaCl 0.9% IV. The rats were killed 4 hours after LPS or SAL infusion.


RESULTS
CL2MDP infusion resulted in a complete KC elimination. KC-depleted rats had the lowest mean arterial pressure, the highest heart and ventilatory rate after endotoxemia. All rats were able to maintain pH in normal ranges. The KC-depleted rats after partial hepatectomy had the lowest CO2 levels and the highest levels of lactate during endotoxemia. Oxygen levels were similar in all groups. Hepatic, pulmonary, and renal mRNA expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta were decreased in KC-depleted rats. Plasma levels of TNF-alpha were significantly decreased in KC-depleted rats. Furthermore, the highest influx of macrophages and polymorphonuclear cells in the lung and kidney were measured in KC-depleted rats during endotoxemia.


CONCLUSIONS
Partial hepatectomy in KC-depleted rats result in a more pronounced endotoxin-mediated systemic inflammation and decreased synthesis of cytokines.
Prins
Hubert A
HA
Department of Surgery, VU Medical Center, Amsterdam, The Netherlands.
Meijer
Catharina
C
Boelens
Petra G
PG
Nijveldt
Robert J
RJ
Siroen
Michiel P C
MP
Masson
Sylvie
S
Daveau
Maryvonne
M
Scotté
Michel
M
Diks
Jeroen
J
van Leeuwen
Paul A M
PA
D000818:Animals; D004002:Clodronic Acid / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D004731:Endotoxins / Q000008:administration & dosage* / Q000633:toxicity; D006498:Hepatectomy; D007728:Kupffer Cells / Q000276:immunology / Q000502:physiology*; D008099:Liver / Q000276:immunology* / Q000601:surgery*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D011183:Postoperative Complications; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms
D016207:Cytokines; D004731:Endotoxins; D004002:Clodronic Acid