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.