Chest
Volume 154, Issue 2, August 2018, Pages 317-325
Journal home page for Chest

Original Research: Critical Care
Ultrastructural Alteration of Pulmonary Capillary Endothelial Glycocalyx During Endotoxemia

https://doi.org/10.1016/j.chest.2018.03.003Get rights and content
Under a Creative Commons license
open access

Background

The most recent diagnostic criteria for sepsis include organ failure. Microvascular endothelial injury is believed to lead to the multiple organ failure seen in sepsis, although the precise mechanism is still controversial. ARDS is the primary complication during the sequential development of multiple organ dysfunction in sepsis, and endothelial injury is deeply involved. Sugar-protein glycocalyx coats all healthy vascular endothelium, and its disruption is one factor believed to contribute to microvascular endothelial dysfunction during sepsis. The goal of this study was to observe the three-dimensional ultrastructural alterations in the pulmonary capillary endothelium, including the glycocalyx, during sepsis-induced pulmonary vasculitis.

Methods

This study investigated the three-dimensional ultrastructure of pulmonary vascular endothelial glycocalyx in a mouse lipopolysaccharide-induced endotoxemia model. Lungs were fixed with lanthanum-containing alkaline fixative to preserve the glycocalyx.

Results

On both scanning and transmission electron microscopic imaging, the capillary endothelial glycocalyx appeared as a moss-like structure entirely covering the endothelial cell surface in normal mice. In the septic lung following liposaccharide injection, however, this structure was severely disrupted; it appeared to be peeling away and coagulated. In addition, syndecan-1 levels were significantly reduced in the septic lung, and numerous spherical structures containing glycocalyx were observed on the endothelial surface.

Conclusions

It appears that endothelial glycocalyx in the lung is markedly disrupted under experimental endotoxemia conditions. This finding supports the notion that disruption of the glycocalyx is causally related to the microvascular endothelial dysfunction that is characteristic of sepsis-induced ARDS.

Key Words

acute lung injury
pathology
sepsis
vasculitis

Abbreviations

LPS
lipopolysaccharide
TEM
transmission electron microscopic

Cited by (0)

Drs Inagawa and Okada contributed equally to the manuscript.

FUNDING/SUPPORT: This study was supported in part by Grants-in-Aid for Scientific Research [Grants 17K11569, 16H05497, 16K20381, 16K09509, and 15K10973] from the Ministry of Education, Science and Culture of Japan.