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Updated: May 25, 2025
Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice
Published on: February 9, 2014
Renal Expression Levels of C5a Receptor and Autophagy-related Beclin-1 and LC3A/B Are Simultaneously Enhanced Under
Özlem Polat1, Gunseli Orhun2, Ilkay Anakli2
1Department of Anesthesiology and Reanimation, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkiye; ozlemp@yahoo.com.tr.
Background/Aim:
Sepsis-induced acute kidney injury is a fatal, potentially reversible clinical condition. C5a receptor (C5aR) has been implied to play pivotal roles in both autophagy and sepsis-induced organ dysfunction. The aim of this study was to demonstrate the effects of intravenous immunoglobulin preparations on the expression of autophagy markers and investigate possible association between C5aR expression and autophagy in the kidney tissue of septic rats.
Materials And Methods:
Sepsis was induced by cecal ligation perforation (CLP) in rats, which were divided into control, sham, CLP+saline, CLP+IgG (250 mg/kg, iv), and CLP+immunoglobulins enriched with immunoglobulin M (IgGAM) (250 mg/kg, iv) groups. Kidney samples were obtained in two sets of experiments to examine the early (1 day) and late (10 days) effects of treatment. Renal expression levels of C5aR, LC3A/B, and beclin-1 were measured using immunoblotting.
Results:
CLP did not enhance the renal expression of autophagy markers or C5aR. Contrariwise, IgG, and IgGAM administration reduced mortality caused by the CLP procedure and significantly increased C5aR, beclin-1, and LC3A/B expression levels in kidney samples of septic rats. Surviving rats had higher renal expression levels of C5aR, beclin-1, and LC3A/B than deceased rats. Expression levels of C5aR, beclin-1, and LC3A/B showed a strong correlation during the early stage of CLP-induced sepsis but not in the late stage.
Conclusion:
Human-derived immunoglobulin preparations may ameliorate sepsis-related organ dysfunction partially through autophagy-related mechanisms. In the early stage of treatment, enhancement of autophagy in the kidney appears to be associated with C5aR expression.
Insights
Intravenous immunoglobulin preparations reduced mortality in septic rats by increasing C5a receptor (C5aR) and autophagy markers in kidneys. This suggests immunoglobulins may treat sepsis-induced acute kidney injury via autophagy.
Area of Science:
- Nephrology
- Immunology
- Cellular Biology
Background:
- Sepsis-induced acute kidney injury (AKI) is a critical condition with high mortality.
- The C5a receptor (C5aR) is implicated in autophagy and organ dysfunction during sepsis.
- Understanding the role of autophagy and C5aR in sepsis-induced AKI is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the effects of intravenous immunoglobulin (IVIg) preparations on autophagy markers in septic rats.
- To explore the association between C5a receptor (C5aR) expression and autophagy in kidney tissue during sepsis.
- To determine if IVIg influences C5aR expression and autophagy in the context of sepsis-induced AKI.
Main Methods:
- Sepsis was induced in rats using cecal ligation and perforation (CLP).
- Rats were treated with saline, IgG, or immunoglobulin M-enriched IgGAM.
- Renal expression of C5aR, LC3A/B, and beclin-1 was measured via immunoblotting at early (1 day) and late (10 days) time points.
Main Results:
- CLP alone did not increase renal autophagy markers or C5aR.
- IVIg (IgG and IgGAM) treatment reduced mortality in septic rats.
- IVIg administration significantly increased renal C5aR, beclin-1, and LC3A/B expression, with higher levels in survivors.
- A strong correlation between C5aR, beclin-1, and LC3A/B was observed in early-stage sepsis.
Conclusions:
- Human-derived immunoglobulin preparations may mitigate sepsis-related organ dysfunction through autophagy-related pathways.
- Enhanced autophagy in the kidney, associated with C5aR expression, may play a role in the early stages of sepsis treatment.
- IVIg shows potential as a therapeutic agent for sepsis-induced AKI by modulating autophagy and C5aR signaling.
