Mechanical stretch and cytokine synthesis in pulmonary endothelial cells

Abstract

The respiratory system is dynamically exposed to physical forces derived from tidal breathing and blood flow. These physical forces are important for maintaining homeostasis of the respiratory system and normal lung development in vivo. In contrast, excessive mechanical forces lead to the pathogenesis of pulmonary diseases. Pulmonary endothelial cells serve as a barrier that regulates fluid balance and inflammatory cell accumulation in the lung. The functions of pulmonary endothelial cells are significantly affected by mechanical stimuli such as shear stress and mechanical stretch. For example, pulmonary endothelial cells produce cytokines/chemokines and nitric oxide in response to mechanical stimuli. The mechanotransduction pathways for mechanical force transmission into the intracellular signals are through mechanosensitive ion channels, integrins, actin cytoskeleton, and activation of mitogen-activated protein-kinases. Alterations in pulmonary endothelial cell properties due to excessive mechanical stress are suggested to play an important role in the disease progression of lung injury and inflammation. This chapter focuses on recent evidence regarding regulation of mechanical stress-induced cytokine/chemokine production by pulmonary endothelial cells and the role of pulmonary endothelial cells in the pathogenesis of pulmonary diseases related to mechanical stress.