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The Role of Kupffer Cells After Major Liver Surgery

Hubert A. Prins^*, Catharina Meijer^*, Petra G. Boelens^*, Robert J. Nijveldt^*, Michiel P. C. Siroen^*, Sylvie Masson, Maryvonne Daveau, Michel Scotté^,, Jeroen Diks^* and Paul A. M. van Leeuwen^*

From the ^* Department of Surgery, VU Medical Center, Amsterdam, The Netherlands; Inserm U 519, Faculté de Médecine et de Pharmacie, Rouen, France; and the Department of General and Digestive Surgery, Charles Nicolle Hospital, Rouen, France

Correspondence: P. A. M. van Leeuwen, MD, PhD, Department of Surgery, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. Electronic mail may be sent to PAM.vLeeuwen{at}vumc.nl.

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% IV. Forty-eight hours later, all rats received a two-thirds liver resection. Twenty-four hours later, rats received at random 50 µg/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- (TNF-) and interleukin-1β were decreased in KC-depleted rats. Plasma levels of TNF- 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.

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