Journal article
Alveolar epithelial glycocalyx degradation mediates surfactant dysfunction and contributes to acute respiratory distress syndrome
JCI insight, Vol.7(2), e154573
01/25/2022
DOI: 10.1172/jci.insight.154573
PMCID: PMC8855818
PMID: 34874923
Abstract
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.
Details
- Title: Subtitle
- Alveolar epithelial glycocalyx degradation mediates surfactant dysfunction and contributes to acute respiratory distress syndrome
- Creators
- Alicia N. Rizzo - Pulmonary and Critical Care AssociatesSarah M. Haeger - Pulmonary and Critical Care AssociatesKaori Oshima - Pulmonary and Critical Care AssociatesYimu Yang - Pulmonary and Critical Care AssociatesAlison M. Wallbank - University of Colorado Anschutz Medical CampusYing Jin - Colorado School of Public HealthMarie Lettau - Charité - Universitätsmedizin BerlinLynda A. McCaig - Western UniversityNancy E. Wickersham - Vanderbilt UniversityJ. Brennan McNeil - Vanderbilt UniversityIgor Zakharevich - University of Colorado Anschutz Medical CampusSarah A. McMurtry - Pulmonary and Critical Care AssociatesChristophe J. Langouët-Astrié - Pulmonary and Critical Care AssociatesKatrina W. Kopf - National Jewish HealthDennis R. Voelker - National Jewish HealthKirk C. Hansen - University of Colorado Anschutz Medical CampusCiara M. Shaver - Vanderbilt UniversityV. Eric Kerchberger - Vanderbilt UniversityRyan A. Peterson - Colorado School of Public HealthWolfgang M. Kuebler - Charité - Universitätsmedizin BerlinMatthias Ochs - Charité - Universitätsmedizin BerlinRuud A.W. VeldhuizenBradford J. Smith - University of Colorado DenverLorraine B. Ware - Vanderbilt UniversityJulie A. Bastarache - Vanderbilt UniversityEric P. Schmidt - Denver Health Medical Center
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.7(2), e154573
- DOI
- 10.1172/jci.insight.154573
- PMID
- 34874923
- PMCID
- PMC8855818
- NLM abbreviation
- JCI Insight
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Publisher
- American Society for Clinical Investigation
- Grant note
- W81XWH-18-0682,R01 HL149422,R01 HL135849,K24 HL103836,F32 HL162230,T32 HL007085,TL1 TR002533,SFB 1449 – B01,CO-M-21-5 / ;
- Language
- English
- Date published
- 01/25/2022
- Academic Unit
- Biostatistics; Internal Medicine
- Record Identifier
- 9984914014102771
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