Alveolar epithelial glycocalyx degradation mediates surfactant dysfunction and contributes to acute respiratory distress syndrome

• DOI: 10.1172/jci.insight.154573
• Publication Date: 2021-12-07T17:02:04Z
• Authors: 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. Lan...; 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
• Keywords: Glycocalyx; Alveolar Epithelium; Diffuse alveolar damage

Acute respiratory distress syndrome (ARDS) is a common cause of failure yet has few pharmacologic therapies, reflecting the mechanistic heterogeneity lung injury. We hypothesized that damage to alveolar epithelial glycocalyx, layer glycosaminoglycans interposed between epithelium and surfactant, contributes injury in patients with ARDS. Using mass spectrometry airspace fluid noninvasively collected from mechanically ventilated patients, we found glycosaminoglycan shedding (an index glycocalyx degradation) occurred predominantly direct was associated duration mechanical ventilation. Male had increased shedding, which correlated concentrations matrix metalloproteinases. Selective degradation mice sufficient induce surfactant dysfunction, key characteristic ARDS, leading microatelectasis decreased compliance. Rapid colorimetric quantification feasible could provide point-of-care prognostic information clinicians and/or be used for predictive enrichment clinical trials.