Renal Expression Levels of C5a Receptor and Autophagy-related Beclin-1 and LC3A/B Are Simultaneously Enhanced Under Immunoglobulin Treatment in a Rat Model of Sepsis.

Abstract

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.