Impaired neutrophil microbicidal activity in rat cholestasis

Abstract

BACKGROUND: Previously, we have documented impaired neutrophil recruitment to inflammatory sites in cholestatic rats. However, there may be additional neutrophil defects that could account for the increased incidence of septic complications in cholestatic patients. The aim of this study was to investigate neutrophil functional defects in cholestasis. METHODS: Sprague-Dawley rats were either bile duct resected (BDR) or sham resected (sham). Five days after surgery, peripheral blood neutrophils were assayed for bacterial killing, phagocytic activity, superoxide anion (O2-) production, and degranulation. RESULTS: BDR neutrophils showed several functional defects. An in vitro killing of Staphylococcus aureus (5 x 10(6) CFU/mL) showed that BDR neutrophils were less efficient at killing bacteria than sham neutrophils. Furthermore, bacterial killing by sham and BDR neutrophils was significantly attenuated in the presence of BDR sera. Phagocytosis and neutrophil degranulation did not seem to contribute to impaired killing in BDR neutrophils. However, a rightward shift was observed in the dose-response curve of N-formyl-methionyl- leucyl-phenylalanine-stimulated BDR neutrophil O2- production. CONCLUSIONS: O2- generation and bacterial killing are depressed in BDR neutrophils, and BDR sera appear to accentuate the defect in BDR neutrophil bacterial killing. These defects may contribute to lowered resistance to microbial invasion in cholestasis. (Gastroenterology 1997 May;112(5):1692-8)