The epithelial and endothelial glycocalyces of the lung during health and lung injury. A: during homeostasis the lung has both a pulmonary endothelial glycocalyx and an alveolar epithelial glycocalyx. Lung injury from inhaled insults (“direct lung injury”) is associated with degradation of the alveolar epithelial glycocalyx. Conversely, lung injury from systemic insults (“indirect lung injury”) is largely characterized by degradation of the pulmonary endothelial glycocalyx. Notably, patients with acute respiratory distress syndrome (ARDS) often have multiple simultaneous insults, which can lead to degradation of both the endothelial and epithelial glycocalyces. B: direct pulmonary insults in mice (lipopolysaccharide, influenza, and bleomycin) induces shedding of heparan sulfate (HS) into the alveolar lining fluid (bronchoalveolar lavage, corrected for urea dilution) (11, 12, 30). C: indirect lung injury in mice (cecal ligation and puncture, CLP) does not induce shedding of HS into the alveolar lining fluid. CLP airspace samples pooled (n = 3/group). D: CLP does induce shedding of HS from the endothelial glycocalyx into the plasma (34). For B and D, n > 5 mice/group. Bars = standard error of the mean. Individual comparisons by t test; multiple comparisons by ANOVA. *P < 0.05. FFU, focus forming unit; IN, intranasal; IT, intratracheal; LPS, lipopolysaccharide. The schematic figure (A) was created using BioRender.