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Inflammatory cell function in young rodents with experimental cholestasis: investigations of functional deficits,
P T Roughneen1, D B Drath, A D Kulkarni
1Department of Surgery, University of Texas Medical School, Houston 77054.
Insights
Cholestasis impairs neutrophil phagocytosis, increasing infection risk in children. This study shows impaired 14C S aureus uptake in cholestatic rats, highlighting a key immune defense defect.
Area of Science:
- Immunology
- Hepatology
- Pediatrics
Background:
- Children with cholestasis face increased susceptibility to infections.
- Impaired host defense mechanisms are implicated in cholestasis-related complications.
- Polymorphonuclear leukocytes (PMNs) play a critical role in immune response.
Purpose of the Study:
- To investigate the impact of cholestasis on systemic polymorphonuclear leukocyte (PMN) function.
- To assess if cholestasis affects PMN chemotaxis, phagocytosis, and superoxide release.
- To determine the in vitro effects of cholestasis on neutrophil immune response.
Main Methods:
- Bile duct ligation (BDL) model in Sprague Dawley rats, with sham (SH) and normal control (NC) groups.
- Isolation of PMNs and sera on day 21 post-operation.
- Assessment of PMN chemotaxis, phagocytosis of 14C-labeled Staphylococcus aureus, and superoxide release.
Main Results:
- Serum bilirubin levels were significantly elevated in the BDL group compared to SH and NC groups.
- PMN phagocytosis of 14C S aureus was significantly impaired in BDL rats at 60, 90, and 120 minutes.
- No significant differences were observed in PMN chemotactic response or superoxide release between the groups.
Conclusions:
- Cholestasis in rats leads to impaired neutrophil phagocytosis in vitro.
- This impaired phagocytosis may contribute to the increased susceptibility to infections observed in cholestatic children.
- Further research is needed to elucidate the precise mechanisms linking cholestasis to compromised neutrophil function.
Abstract:
Children with cholestasis are susceptible to infective complications. This may be attributable to impaired host defense. We postulated that cholestasis affects systemic polymorphonuclear leukocyte (PMN) function by impeding chemotaxis, phagocytosis, and superoxide release, which are all critical in eliciting an adequate immune response. Sprague Dawley rats (225 g) were assigned to three groups: bile duct ligated (BDL), sham (SH), and normal control (NC). On day 21 after operation, PMN and sera were isolated. Chemotactic response to C5a and FMLP (formyl-methionyl-leucyl-phenylalanine), superoxide release, and phagocytic uptake of 14C-labeled Staphylococcus aureus were performed on pooled PMN samples. Results were expressed as mean +/- SD. Serum bilirubin at day 21 was 6.3 +/- 2.9 v 0.1 +/- 0.1 and 0.1 +/- 0 mg/dL (P less than .01) in BDL, SH, and NC groups, respectively. Kinetic studies of PMN phagocytosis demonstrated impaired 14C S aureus uptake by BDL neutrophils at 60 (P less than .05), 90 (P less than .05), and 120 minutes (P less than .05) compared with SH and NC groups. No differences in PMN chemotactic response to C5a and FMLP was observed in BDL, SH and NC groups (43 +/- 14 v 40 +/- 12 and 33 +/- 1, and 43 +/- 20 v 43 +/- 14 and 28 +/- 1 cell per field, respectively). Zymosan stimulated superoxide release did not differ between groups (14.3 +/- 3.6 (BDL) v 15.1 +/- 8.7 (SH) and 12 +/- 2.0 (NC) nmol/30 min/mg cell protein, respectively. Thus, cholestasis impairs neutrophil phagocytosis in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)