ArticleAmerican journal of respiratory cell and molecular biology2018
Epithelial Heparan Sulfate Contributes to Alveolar Barrier Function and Is Shed during Lung Injury.
Article in American journal of respiratory cell and molecular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 64 citations in OpenAlex.
- Plasma Heparan Sulfate Structural Variation and Phenotypic Heterogeneity in Pediatric Acute Respiratory Distress Syndrome.Research square · 2026Article
- Anti-heparanase shields against endothelial dysfunction in a rat model of warm pulmonary ischemia-reperfusion.Respiratory research · 2026Article
- Extracellular Superoxide Dismutase in Acute Respiratory Distress Syndrome: Pathogenic Mechanisms and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2026Review
- Endothelial glycocalyx glycan expression in lymphatic vasculature in mice.Frontiers in cell and developmental biology · 2026Article
- Comparative electron microscopic visualization of the lung alveolar epithelial glycocalyx with different staining and labeling methods.Journal of anatomy · 2025Article
- Burn-Related Glycocalyx Derangement and the Emerging Role of MMP8 in Syndecan Shedding.Biology · 2025Article
- Optimization of chemical transfection in airway epithelial cell lines.BMC biotechnology · 2025Article
- Matrix metalloproteinase-7 is dispensable in a mouse model of sepsis-induced acute lung injury.PloS one · 2025Article
- First contact: an interdisciplinary guide into decoding H5N1 influenza virus interactions with glycosaminoglycans in 3D respiratory cell models.Frontiers in cellular and infection microbiology · 2025Review
- Respiratory Epithelial Cell Surface Decoration Provides Defense against Bacterial Damage during Infection.American journal of respiratory cell and molecular biology · 2024Article
- Cellular Mechanisms of Lung Injury: Current Perspectives.Clinics in chest medicine · 2024Review
- Enzymatic Modulation of the Pulmonary Glycocalyx Enhances Susceptibility toAmerican journal of respiratory cell and molecular biology · 2024Article
- Extracellular glucose triggers metabolic reprogramming of cultured human bronchial epithelial cells and indirect fibroblast activation.FEBS open bio · 2024Article
- Bacterial pneumonia-induced shedding of epithelial heparan sulfate inhibits the bactericidal activity of cathelicidin in a murine model.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- The role of human extracellular matrix proteins in defining Staphylococcus aureus biofilm infections.FEMS microbiology reviews · 2024Review
- Matrix metalloproteinases mediate influenza A-associated shedding of the alveolar epithelial glycocalyx.PloS one · 2024Article
- Vaporization of perfluorocarbon attenuates sea-water-drowning-induced acute lung injury by deactivating the NLRP3 inflammasomes in canines.Experimental biology and medicine (Maywood, N.J.) · 2024Article
- Liraglutide pretreatment attenuates sepsis-induced acute lung injury.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- The unremarkable alveolar epithelial glycocalyx: a thorium dioxide-based electron microscopic comparison after heparinase or pneumolysin treatment.Histochemistry and cell biology · 2023Article
- The role of the alveolar epithelial glycocalyx in acute respiratory distress syndrome.American journal of physiology. Cell physiology · 2023Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
The lung epithelial glycocalyx is a carbohydrate-enriched layer lining the pulmonary epithelial surface. Although epithelial glycocalyx visualization has been reported, its composition and function remain unknown. Using immunofluorescence and mass spectrometry, we identified heparan sulfate (HS) and chondroitin sulfate within the lung epithelial glycocalyx. In vivo selective enzymatic degradation of epithelial HS, but not chondroitin sulfate, increased lung permeability. Using mass spectrometry and gel electrophoresis approaches to determine the fate of epithelial HS during lung injury, we detected shedding of 20 saccharide-long or greater HS into BAL fluid in intratracheal LPS-treated mice. Furthermore, airspace HS in clinical samples from patients with acute respiratory distress syndrome correlated with indices of alveolar permeability, reflecting the clinical relevance of these findings. The length of HS shed during intratracheal LPS-induced injury (≥20 saccharides) suggests cleavage of the proteoglycan anchoring HS to the epithelial surface, rather than cleavage of HS itself. We used pharmacologic and transgenic animal approaches to determine that matrix metalloproteinases partially mediate HS shedding during intratracheal LPS-induced lung injury. Although there was a trend toward decreased alveolar permeability after treatment with the matrix metalloproteinase inhibitor, doxycycline, this did not reach statistical significance. These studies suggest that epithelial HS contributes to the lung epithelial barrier and its degradation is sufficient to increase lung permeability. The partial reduction of HS shedding achieved with doxycycline is not sufficient to rescue epithelial barrier function during intratracheal LPS-induced lung injury; however, whether complete attenuation of HS shedding is sufficient to rescue epithelial barrier function remains unknown.
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