4680 Reversibility of kupffer cells dysfunction in rats with obstructive jaundic: phagocytic function and production of reactive oxygen species evaluated by flow cytometry.

Abstract

Background: The function of the reticuloendothelial system is impaired in obstructive jaundice. The effects of obstructive jaundice on Kupffer cells and the influence of internal and external drainage are unclear. Aims: To study the effect of internal and external drainage on Kupffer cell phagocytosis and production of reactive oxygen species in rats with obstructive jaundice. Materials and Methods: Fifty male Sprague-Dawley rats weighing 300-350 g were randomly assigned to 4 groups: sham operation (SH, n = 11), obstructive jaundice by bile duct ligation and division (OJ, n = 12), internal drainage by choledochoduodenostomy (ID, n = 13) and external drainage by exteriorizing a biliary drainage tube at the nape (ED, n = 14) on day 7 after bile duct ligation. Kupffer cells were isolated by flow cytometric sorting 7 days later. The phagocytic function of the Kupffer cells was measured by flow cytometry using fluorescent microspheres (1.72 μm). The production of reactive oxygen species (ROS) was assayed by flow cytometry using dihydrorhodamine 123 (DHR) with phorbol myristate acetate (PMA) as an activator. Results: The phagocytic function was suppressed in OJ rats (20.8±7.4%) compared with SH rats (41.3±23.2%) (P=0.007). After drainage procedures, the depressed Kupffer cell function was reversed by ID (37.0±15.2%) (P=0.036), but not by ED (21.6±7.0%) (P=1.000). The release of ROS was higher in the OJ rats (1.35±0.36) than in the SH rats (0.98±0.09) (P=0.042). After drainage, the ROS production returned to normal levels in the ID rats (0.97±0.11) (P=0.032), but remained high in the ED rats (1.35±0.46) (P=1.000). Conclusion: Kupffer cell functions, including phagocytosis and release of reactive oxygen species, are impaired in obstructive jaundice. Internal biliary drainage, but not external drainage, causes recovery of Kupffer cell functions.