The Lung Endothelial Barrier in Acute Inflammation

Müller-Redetzky, Holger C.; Lienau, Jasmin; Witzenrath, Martin

In the lungs, alveolar endo- and epithelial cells and their merged basal laminae form a delicate membrane, which allows rapid and effective gas exchange between alveolar and vascular lumen and, at the same time, provides a barrier to protect against inhaled particles and pathogens. Following infectious or sterile inflammatory conditions, strictly controlled endothelial leakiness is required for leukocyte transmigration. However, increased permeability caused by host-dependent inflammatory mechanisms or pathogen-induced endothelial injury may lead to uncontrolled protein-rich fluid extravasation, lung edema and finally acute respiratory distress syndrome (ARDS), which still carries an unacceptably high mortality rate. This chapter gives an overview of major mechanisms underlying pulmonary endothelial barrier regulation and disruption, focusing on the role of specific cell populations, complement and coagulation systems and mediators including angiopoietins, sphingolipids, adrenomedullin, as well as reactive oxygen and nitrogen species in the regulation of pulmonary vascular permeability. Further, current therapeutic strategies targeting the pulmonary endothelial barrier to improve barrier function are discussed.