Alveolar epithelial glycocalyx degradation mediates surfactant dysfunction and contributes to acute respiratory distress syndrome
Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure yet has few pharmacologic therapies, reflecting the mechanistic heterogeneity of lung injury. We hypothesized that damage to the alveolar epithelial glycocalyx, a layer of glycosaminoglycans interposed between the ep...
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2022-01-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.154573 |
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| author | Alicia N. Rizzo Sarah M. Haeger Kaori Oshima Yimu Yang Alison M. Wallbank Ying Jin Marie Lettau Lynda A. McCaig Nancy E. Wickersham J. Brennan McNeil Igor Zakharevich Sarah A. McMurtry Christophe J. Langouët-Astrié Katrina W. Kopf Dennis R. Voelker Kirk C. Hansen Ciara M. Shaver V. Eric Kerchberger Ryan A. Peterson Wolfgang M. Kuebler Matthias Ochs Ruud A.W. Veldhuizen Bradford J. Smith Lorraine B. Ware Julie A. Bastarache Eric P. Schmidt |
| author_facet | Alicia N. Rizzo Sarah M. Haeger Kaori Oshima Yimu Yang Alison M. Wallbank Ying Jin Marie Lettau Lynda A. McCaig Nancy E. Wickersham J. Brennan McNeil Igor Zakharevich Sarah A. McMurtry Christophe J. Langouët-Astrié Katrina W. Kopf Dennis R. Voelker Kirk C. Hansen Ciara M. Shaver V. Eric Kerchberger Ryan A. Peterson Wolfgang M. Kuebler Matthias Ochs Ruud A.W. Veldhuizen Bradford J. Smith Lorraine B. Ware Julie A. Bastarache Eric P. Schmidt |
| author_sort | Alicia N. Rizzo |
| collection | DOAJ |
| description | Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure yet has few pharmacologic therapies, reflecting the mechanistic heterogeneity of lung injury. We hypothesized that damage to the alveolar epithelial glycocalyx, a layer of glycosaminoglycans interposed between the epithelium and surfactant, contributes to lung injury in patients with ARDS. Using mass spectrometry of airspace fluid noninvasively collected from mechanically ventilated patients, we found that airspace glycosaminoglycan shedding (an index of glycocalyx degradation) occurred predominantly in patients with direct lung injury and was associated with duration of mechanical ventilation. Male patients had increased shedding, which correlated with airspace concentrations of matrix metalloproteinases. Selective epithelial glycocalyx degradation in mice was sufficient to induce surfactant dysfunction, a key characteristic of ARDS, leading to microatelectasis and decreased lung compliance. Rapid colorimetric quantification of airspace glycosaminoglycans was feasible and could provide point-of-care prognostic information to clinicians and/or be used for predictive enrichment in clinical trials. |
| first_indexed | 2024-12-12T13:42:06Z |
| format | Article |
| id | doaj.art-31aa2a1550884c5a8f8b113a7914671a |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-12-12T13:42:06Z |
| publishDate | 2022-01-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-31aa2a1550884c5a8f8b113a7914671a2022-12-22T00:22:46ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-01-0172Alveolar epithelial glycocalyx degradation mediates surfactant dysfunction and contributes to acute respiratory distress syndromeAlicia N. RizzoSarah M. HaegerKaori OshimaYimu YangAlison M. WallbankYing JinMarie LettauLynda A. McCaigNancy E. WickershamJ. Brennan McNeilIgor ZakharevichSarah A. McMurtryChristophe J. Langouët-AstriéKatrina W. KopfDennis R. VoelkerKirk C. HansenCiara M. ShaverV. Eric KerchbergerRyan A. PetersonWolfgang M. KueblerMatthias OchsRuud A.W. VeldhuizenBradford J. SmithLorraine B. WareJulie A. BastaracheEric P. SchmidtAcute respiratory distress syndrome (ARDS) is a common cause of respiratory failure yet has few pharmacologic therapies, reflecting the mechanistic heterogeneity of lung injury. We hypothesized that damage to the alveolar epithelial glycocalyx, a layer of glycosaminoglycans interposed between the epithelium and surfactant, contributes to lung injury in patients with ARDS. Using mass spectrometry of airspace fluid noninvasively collected from mechanically ventilated patients, we found that airspace glycosaminoglycan shedding (an index of glycocalyx degradation) occurred predominantly in patients with direct lung injury and was associated with duration of mechanical ventilation. Male patients had increased shedding, which correlated with airspace concentrations of matrix metalloproteinases. Selective epithelial glycocalyx degradation in mice was sufficient to induce surfactant dysfunction, a key characteristic of ARDS, leading to microatelectasis and decreased lung compliance. Rapid colorimetric quantification of airspace glycosaminoglycans was feasible and could provide point-of-care prognostic information to clinicians and/or be used for predictive enrichment in clinical trials.https://doi.org/10.1172/jci.insight.154573Pulmonology |
| spellingShingle | Alicia N. Rizzo Sarah M. Haeger Kaori Oshima Yimu Yang Alison M. Wallbank Ying Jin Marie Lettau Lynda A. McCaig Nancy E. Wickersham J. Brennan McNeil Igor Zakharevich Sarah A. McMurtry Christophe J. Langouët-Astrié Katrina W. Kopf Dennis R. Voelker Kirk C. Hansen Ciara M. Shaver V. Eric Kerchberger Ryan A. Peterson Wolfgang M. Kuebler Matthias Ochs Ruud A.W. Veldhuizen Bradford J. Smith Lorraine B. Ware Julie A. Bastarache Eric P. Schmidt Alveolar epithelial glycocalyx degradation mediates surfactant dysfunction and contributes to acute respiratory distress syndrome JCI Insight Pulmonology |
| title | Alveolar epithelial glycocalyx degradation mediates surfactant dysfunction and contributes to acute respiratory distress syndrome |
| title_full | Alveolar epithelial glycocalyx degradation mediates surfactant dysfunction and contributes to acute respiratory distress syndrome |
| title_fullStr | Alveolar epithelial glycocalyx degradation mediates surfactant dysfunction and contributes to acute respiratory distress syndrome |
| title_full_unstemmed | Alveolar epithelial glycocalyx degradation mediates surfactant dysfunction and contributes to acute respiratory distress syndrome |
| title_short | Alveolar epithelial glycocalyx degradation mediates surfactant dysfunction and contributes to acute respiratory distress syndrome |
| title_sort | alveolar epithelial glycocalyx degradation mediates surfactant dysfunction and contributes to acute respiratory distress syndrome |
| topic | Pulmonology |
| url | https://doi.org/10.1172/jci.insight.154573 |
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