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Characterization of the defects in murine peritoneal macrophage function in the early postsplenectomy period
J E McCarthy1, P H Redmond, S M Duggan
1Department of Pathology, Beaumont Hospital, Dublin, Ireland.
Abstract:
Postsplenectomy bacterial sepsis may be fatal, due to defects in both cellular and humoral immune responses. The objective of this study was to assess the efficacy of peritoneal macrophage antibacterial function in the early postsplenectomy period. Murine models of splenectomy and sham operation were characterized and peritoneal macrophages were harvested 24 h to 1 wk after surgery. Cells from splenectomized animals demonstrated a nonsignificant delay in phagocytosis of Escherichia coli at 24 h with, however, significantly impaired killing of intracellular organisms at 24 h and 1 wk compared to the sham group. Paradoxically, the production of the macrophage antibacterial product superoxide anion was not impaired at either time point in the splenectomy group compared with sham-operated and control mice. Nitric oxide release was significantly lower in the splenectomized group (p = 0.006), a possible explanation for reduced bacterial killing. Mortality from bacterial peritonitis was significantly higher with concomitant splenectomy than in the sham splenectomy group at 24 h (p < 0.02). The production of TNF from macrophages was up-regulated immediately following splenectomy, a cytokine which may contribute to mortality from bacteremic shock. Local defects in macrophage antimicrobial function may contribute significantly to bacteremia and to subsequent mortality in the early postsplenectomy period.
Insights
Splenectomy impairs peritoneal macrophage antibacterial function, leading to increased mortality from bacterial infections. This study highlights early immune defects after spleen removal, impacting sepsis outcomes.
Area of Science:
- Immunology
- Surgical Pathology
Background:
- Post-splenectomy sepsis poses a significant mortality risk.
- Immune system defects, both cellular and humoral, contribute to this risk.
Purpose of the Study:
- To evaluate the antibacterial function of peritoneal macrophages in the early period following splenectomy.
- To investigate the impact of splenectomy on macrophage-mediated bacterial clearance and survival.
Main Methods:
- Utilized murine models of splenectomy and sham operations.
- Harvested peritoneal macrophages at 24 hours and 1 week post-surgery.
- Assessed phagocytosis, intracellular killing of Escherichia coli, nitric oxide, superoxide anion, and TNF production.
Main Results:
- Splenectomized mice showed impaired intracellular bacterial killing and reduced nitric oxide production.
- Mortality from bacterial peritonitis was significantly higher in splenectomized mice.
- Tumor Necrosis Factor (TNF) production was upregulated post-splenectomy.
Conclusions:
- Early postsplenectomy period is characterized by local defects in macrophage antimicrobial function.
- Reduced nitric oxide release and altered cytokine profiles may explain impaired bacterial killing and increased mortality.
- Macrophage dysfunction contributes significantly to sepsis and mortality after splenectomy.