Epithelial dysfunction in acute lung injury.

Abstract

More than a quarter century has passed since Ashbaugh and colleagues postulated that abnormalities of surfactant are causally related to the abrupt and severe organ dysfunction that occurs in individuals with acute lung injury (ALI). In this time, much progress has been made in expanding our understanding of the normal functions of the alveolar epithelium and how these functions may be disrupted in the context of ALI. Alveolar epithelial cells are a key structural component of the spatial separation of gas and plasma, essential for normal gas exchange in the lung. In addition, alveolar epithelial cells synthesize, secrete, and take up surfactant, which, by reducing surface tension, is a key determinant of intra-alveolar pressure. Surfactant is qualitatively and quantitatively abnormal in lung injury due to changes in synthesis, secretion, intra-alveolar metabolism, and biophysical inhibition by protein and lipid inhibitors. Alveolar epithelial cells also subserve additional host defense functions, such as modulation of lymphocyte, macrophage, and neutrophil function; production of prostanoids, complement proteins, and nitric oxide; and display of major histocompatibility complex II molecules and intracellular adhesion molecule-1. Although the physiologic and pathogenic significance of some these functions is not absolutely clear, they are of potential relevance in the context of lung injury, wherein they may participate in the process of alveolar injury and repair.