Editorial: Molecular mechanisms of lung endothelial permeability

Molecular mechanisms of lung endothelial permeabilityLung endothelium regulates movement of fluid, macromolecules, and leukocytes into the interstitium and subsequently into the alveolar air spaces.The monolayer of endothelial cells (ECs) lining the blood vessels are in close contact and tight association with each other forming a tight barrier (Komarova and Malik, 2010;Wettschureck et al., 2019).Any breach in the endothelial barrier results in the uncontrolled movement of fluid, macromolecules and leukocytes into the interstitium and pulmonary air spaces causing pulmonary edema and inflammation (Ware and Matthay, 2000;Johnson and Matthay, 2010).Therefore, the integrity of the pulmonary EC monolayer is a critical requirement for preservation of pulmonary function.Disruption of lung endothelial barrier occurs during the inflammatory disease states such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), which remain a major cause of morbidity and mortality with an overall mortality rate of 25%-40% (Rubenfeld et al., 2005;Maca et al., 2017).The pharmacological treatment of ALI remains nonspecific and relies on supportive care and control of initiating causes (Gonzales et al., 2015; Huppert et al., 2019).Therefore, novel therapies are urgently sought after to improve the clinical outcomes.This special issue provides an overview of recent studies in the field of lung endothelial permeability with the goal to advance our knowledge of the mechanisms of pulmonary endothelial barrier regulation.We hope that it will help to identify novel strategies and pharmacologic agonists for therapeutic intervention of ALI/ARDS.Permeability across endothelial and epithelial cell monolayers can involve transcellular and paracellular transport or both pathways (Komarova and Malik, 2010;Wettschureck et al., 2019).However, the majority of trafficking occurs through the paracellular pathway (Komarova and Malik, 2010;Wettschureck et al., 2019).Paracellular permeability is determined by equilibrium of the competing contractile forces, which generate centripetal tension via activation of the actomyosin contractile machinery and adhesive cell-cell and cell-matrix tethering forces, which depend upon the adhesive