Ultrastructural Alteration of Pulmonary Capillary Endothelial Glycocalyx During Endotoxemia

Chest: The Journal of Circulation, Respiration and Related Systems

Risa Inagawa^1¹  Hideshi Okada^1²  Kodai Suzuki^1³  Genzou Takemura^2⁴ 

[1] Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan^1;Department of Internal Medicine, Asahi University School of Dentistry, Mizuho, Japan^2;Laboratory of Molecular Biology, Department of Biofunctional Analysis, Gifu Pharmaceutical University, Gifu, Japan^4;Research Institute for Biotechnology, Asahi University School of Dentistry, Mizuho, Japan^3

关键词: acute lung injury;    pathology;    sepsis;    vasculitis;    LPS;    lipopolysaccharide;    TEM;    transmission electron microscopic;   

DOI  :  10.1016/j.chest.2018.03.003

学科分类：呼吸医学

来源: American College of Chest Physicians

【 摘 要 】

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.

【 授权许可】

CC BY