Neutrophil Elastase Damages the Pulmonary Endothelial Glycocalyx in Lipopolysaccharide-Induced Experimental Endotoxemia

Suzuki, Kodai; Okada, Hideshi; Takemura, Genzou; Takada, Chihiro; Kuroda, Ayumi; Yano, Hirohisa; Zaikokuji, Ryogen; Morishita, Kentaro; Tomita, Hiroyuki; Oda, Kazumasa; Matsuo, Saori; Uchida, Akihiro; Fukuta, Tetsuya; Sampei, So; Miyazaki, Nagisa; Kawaguchi, Tomonori; Watanabe, Takatomo; Yoshida, Takahiro; Ushikoshi, Hiroaki; Yoshida, Shozo; Maekawa, Yoichi; Ogura, Shinji

doi:10.1016/j.ajpath.2019.05.002

Cited by 60 publications

(48 citation statements)

References 33 publications

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“…The endothelial GCX can be injured under various pathologic conditions, including sepsis, inflammation, operative stress, and diabetes [1][2][3][4]. Several clinical biomarkers for GCX injury have been reported, such as serum concentration of syndecan-1, heparin sulfate, and hyaluronic acid, reflecting the degrees of their shedding off from the endothelial surface into the bloodstream [22][23][24]. These markers may be useful for the evaluation of systemic injury of endothelial GCX, but evaluation of local injury in each organ and tissue is necessary for the evaluation of pathogenesis of organspecific diseases associated with endothelial injury.…”

Section: Discussionmentioning

confidence: 99%

“…Evaluation of endothelial GCX is useful for understanding the pathogenesis of human diseases associated with endothelial injury and vascular hyperpermeability. The structure of endothelial GCX is injured in sepsis [9,[22][23][24]35], and its thickness is reduced in experimental animal diabetic models [39][40][41][42][43][44]. In these studies, the specimens were perfused with a cationic substrate to detect endothelial GCX, which limits its use in animal experiments.…”

Section: Discussionmentioning

confidence: 99%

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Three-dimensional electron microscopy for endothelial glycocalyx observation using Alcian blue with silver enhancement

et al. 2020

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Glycocalyx (GCX) is a thin layer of negatively charged glycoproteins that covers the vascular endothelial surface and regulates various biological processes. Because of the delicate and fragile properties of this structure, it is difficult to detect GCX morphologically. We established a simple method for a three-dimensional visualization of endothelial GCX using low-vacuum scanning electron microscopy (LVSEM) on formalin-fixed paraffin-embedded (FFPE) sections. Mouse kidney tissue was fixed with 10% buffered formalin containing 1% Alcian blue (ALB) via perfusion and immersion. FFPE sections were observed by light microscopy (LM) and LVSEM, and formalin-fixed epoxy resin-embedded ultrathin sections were observed by transmission electron microscopy (TEM). The endothelial GCX from various levels of kidney blood vessels was stained blue in LM and confirmed as a thin osmiophilic layer in TEM. In LVSEM, the sections stained by periodic acid methenamine silver (PAM) revealed the endothelial GCX as a layer of dense silver-enhanced particles, in both the samples fixed via perfusion and immersion. Correlative light and electron microscopy (CLEM) revealed the fine visible structure of endothelial GCX. This simple method using FFPE samples with ALB will enable the three-dimensional evaluation of endothelial GCX alterations in various human diseases associated with endothelial injury in future studies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Three-dimensional electron microscopy for endothelial glycocalyx observation using Alcian blue with silver enhancement

et al. 2020

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“…Elastase can degrade pulmonary extracellular matrix proteins and cleave epithelial-cadherin to break respiratory cell-cell adhesion. Moreover, elastase has been shown to damage pulmonary vascular endothelial glycocalyx during the pulmonary inflammatory process [ [77] , [78] , [79] ]. Myeloperoxidase, the other primary granular enzyme, catalyzes H 2 O 2 to produce toxic ROS, which has been demonstrated to be a local mediator of alveolar damage [ 80 ].…”

Section: Role Of Neutrophils In Ardsmentioning

confidence: 99%

Understanding the role of neutrophils in acute respiratory distress syndrome

et al. 2021

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Acute respiratory distress syndrome (ARDS) is difficult to treat and is associated with a high mortality rate. The most severe form of coronavirus disease 2019 (COVID-19) also leads to life-threatening ARDS. Neutrophil counts are positively correlated with disease severity in ARDS. Neutrophil activation not only plays a significant role in immune defense against infections, but also causes tissue damage and leads to inflammatory diseases. Activated neutrophils rapidly migrate to inflamed lung tissue, releasing toxic granular contents and generating neutrophil extracellular traps. In the last few decades, it has become apparent that neutrophils occupy a central role in ARDS pathology. In this review, we summarize the neutrophil inflammatory responses and their relationships to ARDS. According to the current literature, understanding the function of neutrophils may be helpful in the treatment of ARDS.

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“…Additionally, Ma et al [35] reported that neutrophils were involved in regulating the microvascular endothelial permeability. Suzuki et al [36] reported that neutrophil elastase damaged the pulmonary endothelial glycocalyx in LPS-induced endotoxemia. In the present study, pretreatment with crocin significantly improved the neutrophil adhesion or infiltration induced by LPS in ARDS mice.…”

Section: Figmentioning

confidence: 99%

Crocin alleviates lipopolysaccharide-induced acute respiratory distress syndrome by protecting against glycocalyx damage and suppressing inflammatory signaling pathways

Zhang

Zhu

et al. 2020

Inflamm. Res.

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Objective To explore the mechanisms of crocin against glycocalyx damage and inflammatory injury in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) mice and LPS-stimulated human umbilical vein endothelial cells (HUVECs). Methods Mice were randomly divided into control, LPS, and crocin + LPS (15, 30, and 60 mg/kg) groups. HUVECs were separated into eight groups: control, crocin, matrix metalloproteinase 9 inhibitor (MMP-9 inhib), cathepsin L inhibitor (CTL inhib), LPS, MMP-9 inhib + LPS, CTL inhib + LPS, and crocin + LPS. The potential cytotoxic effect of crocin on HUVECs was mainly evaluated through methylthiazolyldiphenyl-tetrazolium bromide assay. Histological changes were assessed via hemotoxylin and eosin staining. Lung capillary permeability was detected on the basis of wet-dry ratio and through fluorescein isothiocyanate-albumin assay. Then, protein levels were detected through Western blot analysis, immunohistochemical staining, and immunofluorescence. Results This study showed that crocin can improve the pulmonary vascular permeability in mice with LPS-induced ARDS and inhibit the inflammatory signaling pathways of high mobility group box, nuclear factor κB, and mitogen-activated protein kinase in vivo and in vitro. Crocin also protected against the degradation of endothelial glycocalyx heparan sulfate and syndecan-4 by inhibiting the expressions of CTL, heparanase, and MMP-9 in vivo and in vitro. Overall, this study revealed the protective effects of crocin on LPS-induced ARDS and elaborated their underlying mechanism. Conclusion Crocin alleviated LPS-induced ARDS by protecting against glycocalyx damage and suppressing inflammatory signaling pathways.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Neutrophil Elastase Damages the Pulmonary Endothelial Glycocalyx in Lipopolysaccharide-Induced Experimental Endotoxemia

Cited by 60 publications

References 33 publications

Three-dimensional electron microscopy for endothelial glycocalyx observation using Alcian blue with silver enhancement

Three-dimensional electron microscopy for endothelial glycocalyx observation using Alcian blue with silver enhancement

Understanding the role of neutrophils in acute respiratory distress syndrome

Crocin alleviates lipopolysaccharide-induced acute respiratory distress syndrome by protecting against glycocalyx damage and suppressing inflammatory signaling pathways

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