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Reticuloendothelial function and plasma fibronectin in a murine model of intra-abdominal sepsis
G E Jones1, L R Purves, T M de Chalain
1Department of Surgery, University of Cape Town, South Africa.
Abstract:
The lung is the target organ most frequently involved in the early phase of multiple organ failure. Microembolisation of the pulmonary vasculature by bacterial and non-bacterial particles and debris with failure of the clearance mechanism of the reticuloendothelial system (RES) and depletion of plasma fibronectin have been implicated in the pathogenesis. The present study examined the concurrent changes in plasma fibronectin, RES phagocytic function, organ localisation of bacterial and non-bacterial particles and the levels of circulating endotoxin and fibrin degradation products in a clinically relevant murine model of severe intra-abdominal infection. Progressive sepsis was associated with deteriorating RES phagocytic function to 45% of control values within 48 h of sepsis induction. There was decreased hepatosplenic uptake and increased pulmonary localisation of bacterial and lipid emulsion particles. Plasma fibronectin increased in septic animals within 48 h suggesting increased fibronectin production. These changes would support the hypothesis that altered RES function may facilitate pulmonary microembolisation in the pathogenesis of septic multiple organ failure.
Insights
Altered reticuloendothelial system (RES) function and reduced particle clearance in sepsis contribute to lung microembolisation. This suggests a key mechanism in the development of multiple organ failure during severe infection.
Area of Science:
- Pathophysiology
- Immunology
- Critical Care Medicine
Background:
- The lung is a primary target organ in early multiple organ failure.
- Pulmonary microembolisation, reticuloendothelial system (RES) dysfunction, and fibronectin depletion are implicated in its pathogenesis.
- Understanding these mechanisms is crucial for treating severe sepsis.
Purpose of the Study:
- To investigate changes in plasma fibronectin, RES phagocytic function, particle localization, endotoxin, and fibrin degradation products in a murine model of severe intra-abdominal infection.
- To elucidate the role of RES function in pulmonary microembolisation during sepsis.
Main Methods:
- A clinically relevant murine model of severe intra-abdominal infection was utilized.
- Concurrent measurements of plasma fibronectin, RES phagocytic function, organ particle localization (bacterial and lipid emulsions), circulating endotoxin, and fibrin degradation products were performed.
- Septic and control groups were compared over 48 hours.
Main Results:
- Progressive sepsis led to a significant decline in RES phagocytic function (to 45% of control values within 48 hours).
- Hepatosplenic uptake of particles decreased, while pulmonary localization increased.
- Plasma fibronectin levels rose in septic animals, indicating increased production.
Conclusions:
- Altered RES function in sepsis impairs particle clearance, facilitating pulmonary microembolisation.
- These findings support the hypothesis that RES dysfunction is a key factor in the pathogenesis of septic multiple organ failure.
- Targeting RES function may offer therapeutic strategies for sepsis-induced organ damage.