Cyclic stretch induces both apoptosis and secretion in rat alveolar type II cells

Abstract

We examined the effects of short-term cyclic stretch on both phosphatidylcholine (PC) secretion and apoptosis in primary cultures of rat alveolar type II cells. A 22% cyclic stretch (3 cycles/min) was applied to type II cells cultured on silastic membranes using a Flexercell strain unit. This induced, after a lag period of about 1 h, a small, but significant release of [ Q H]PC from prelabelled cells. In addition, stretch increased nuclear condensation, the generation of oligosomal DNA fragments and the activation of caspases. Similar responses were triggered by sorbitol-induced osmotic shock, but not by the secretagogue ATP. We conclude that stretch can induce both apoptosis and PC secretion in alveolar type II cells and propose that these diverse responses occur within the lung as a consequence of normal respiratory distortion of the alveolar epithelium.z 1999 Federation of European Biochemical Societies.

Apoptosis in Lung Development and Neonatal Lung Injury

“…A role for stretch-induced apoptosis in lung development was first suggested by De Paepe et al (11), who showed that depletion of AEC2 after tracheal ligation in fetal rabbits was at least in part due to an increase in apoptosis. Similarly, 20% radial elongation stimulated apoptotic activity in primary adult AEC2 (35). However, these studies performed tissue distension under conditions greater than those considered "physiologic" during gestation.…”

Acoustically detectable cellular-level lung injury induced by fluid mechanical stresses in microfluidic airway systems

“…Mechanical stresses have been shown to play an important role in regulating various functions of pulmonary epithelial cells such as growth (1)(2)(3), apoptosis (4-7), migration (8,9), surfactant metabolism (1,6,(10)(11)(12), synthesis of extracellular matrix proteins (11,13), and transport of fluids and ions (12,14,15). Disruption of the local mechanical environment of the pulmonary epithelium often elicits abnormal cellular responses and can contribute to the pathogenesis and progression of various respiratory diseases (4,5,(15)(16)(17)(18)(19)(20).…”

Mechanical Forces Impair Alveolar Ion Transport Processes – A Putative Mechanism Contributing to the Formation of Pulmonary Edema

“…Mechanical distention of isolated and cultivated fetal alveolar cells promotes their differentiation to AT I cells whereas that lack of distention promotes the differentiation to ATII cells (Edwards, 2001). Besides affecting cell differentiation and lung development there is also evidence for the contribution of physical stress as a factor that mediates production and secretion of surfactant proteins by ATII cells (Edwards et al, 1999) as well as by cultured H441 cells (Sanchez-Esteban et al, 1998). There is also evidence that mechanical forces induce apoptosis in ATII cells (Edwards et al, 1999;Hammerschmidt et al, 2007).…”