Sepsis induces an early impairment of endothelial glycocalyx in glomerular capillaries

Introduction

The increase in endothelial capillary permeability represents one of the early and significant hallmarks of sepsis. An inflammatory-induced damage in endothelial glycocalyx has been identified as the mechanism involved in this increase in permeability in the condition of ischemia–reperfusion [1]. To date no data are available for glycocalyx damage in sepsis. The aim of this study was to evaluate whether sepsis-associated increase of permeability is due to glycocalyx alteration.

Methods

To induce sepsis, the cecal ligation and puncture (CLP), a clinically relevant model of polymicrobial infection that mimics human sepsis, was used [2]. Nine rats underwent CLP, two rats, receiving laparotomy only, served as control. Rats were then transcardially perfused with PBS and PBS + paraformaldehyde 4% at three different time points (3, 7 and 15 hours after CLP). Kidneys were collected and processed for light and confocal microscopy examination. Alterations in glycocalyx were studied using digoxigenin-labelled lectin maackia amurensis agglutinin (MMA) (to identify sialic acids, a large family of nine-carboxylated sugars present on the cell surface) and mouse monoclonal antibody against Syndecan-1 (an integral membrane proteoglycan).

Results

In control rats, the luminal surface of the glomerular endothelium appeared intensely stained for MMA lectin and Syndecan-1, indicating the presence of normal glycocalyx. Since its early phase (3 hours), sepsis induced a significant alteration in the glomerular endothelial glycocalyx, which worsened at later time points (7 and 15 hours). At 15 hours, disruption of the glomerular architecture was also present.

Conclusion

Alterations in endothelial glycocalyx may represent the first step of sepsis-related changes in permeability. It is likely that treatments aimed at preserving glycocalyx may also prevent not only the increase in permeability but possibly glomerular disruption.