IMPAIRED NEUTROPHIL MICROBICIDAL ACTIVITY IN RAT CHOLESTASIS

Background: Previously, we have documented impaired neutrophil recruit ment to inflammatory sites in cholestatic rats. However, there may be additional neutrophil defects that could account for the increased inc idence of septic complications in cholestatic patients. The aim of thi s study was to investigate neutrophil functional defects in cholestasi s. Methods: Sprague-Dawley rats were either bile duct resected (BDR) o r sham resected (sham). Five days after surgery, peripheral blood neut rophils were assayed for bacterial killing, phagocytic activity, super oxide anion (O-2(-)) production, and degranulation. Results: BDR neutr ophils showed several functional defects. An in vitro killing of Staph ylococcus aureus (5 x 10(6) CFU/mL) showed that BDR neutrophils were l ess efficient at killing bacteria than sham neutrophils. Furthermore, bacterial killing by sham and BDR neutrophils was significantly attenu ated in the presence of BDR sera. Phagocytosis and neutrophil degranul ation did not seem to contribute to impaired killing in BDR neutrophil s. However, a rightward shift was observed in the dose-response curve of N-formyl-methionyl-leucyl-phenylalanine-stimulated BDR neutrophil O -2(-) production. Conclusions: O-2(-) generation and bacterial killing are depressed in BDR neutrophils, and BDR sera appear to accentuate t he defect in BDR neutrophil bacterial killing. These defects may contr ibute to lowered resistance to microbial invasion in cholestasis.