Variable stretch pattern enhances surfactant secretion in alveolar type II cells in culture

Abstract

Secretion of pulmonary surfactant that maintains low surface tension within the lung is primarily mediated by mechanical stretching of alveolar epithelial type II (AEII) cells. We have shown that guinea pigs ventilated with random variations in frequency and tidal volume had significantly larger pools of surfactant in the lung than animals ventilated in a monotonous manner. Here, we test the hypothesis that variable stretch patterns imparted on the AEII cells results in enhanced surfactant secretion. AEII cells isolated from rat lungs were exposed to equibiaxial strains of 12.5, 25, or 50% change in surface area (DeltaSA) at 3 cycles/min for 15, 30, or 60 min. (3)H-labeled phosphatidylcholine release and cell viability were measured 60 min following the onset of stretch. Whereas secretion increased following 15-min stretch at 50% DeltaSA and 30-min stretch at 12.5% DeltaSA, 60 min of cyclic stretch diminished surfactant secretion regardless of strain. When cells were stretched using a variable strain profile in which the amplitude of each stretch was randomly pulled from a uniform distribution, surfactant secretion was enhanced both at 25 and 50% mean DeltaSA with no additional cell injury. Furthermore, at 50% mean DeltaSA, there was an optimum level of variability that maximized secretion implying that mechanotransduction in these cells exhibits a phenomenon similar to stochastic resonance. These results suggest that application of variable stretch may enhance surfactant secretion, possibly reducing the risk of ventilator-induced lung injury. Variable stretch-induced mechanotransduction may also have implications for other areas of mechanobiology.

Can tidal breathing with deep inspirations of intact airways create sustained bronchoprotection or bronchodilation?

“…Functional changes to the ASM due to chronic inflammation could potentially inhibit these stretch-induced mechanisms in asthma (18). Alternatively, stretch-activated surfactant release could also be responsible for the bronchoprotective effect of the DI (2,35,63). Our group has also provided some evidence that prohibition of DIs in healthy subjects might simply cause atelectasis, which amplifies reactivity (6).…”

“…In protocol 1, it was found that Ptm oscillation from 5-20 cmH 2 O results in significant dilation (36% recovery). In protocol 2, airways were either exposed to large Ptm oscillations before and during constriction (Pre ϩ Post) or only following constriction against a static load (Post Only).…”

Fate of Distal Lung Epithelium Cultured in a Decellularized Lung Extracellular Matrix

“…30 Additionally, distension favors expression of the type I alveolar epithelial cell phenotype, the cells most important for gas exchange in the lung, 31 while variable stretch can increase surfactant secretion by type II alveolar epithelial cells. 32 In our system, ventilation with culture medium may also confer benefits with respect to nutrient and oxygen transport. This may have played a role in the observed EMT as physiological stress and hypoxia may be involved in inducing EMT.…”

Systems Biology and Clinical Practice in Respiratory Medicine. The Twain Shall Meet

“…More importantly, the variability of the breathing pattern itself has also been found to upregulate surfactant secretion (18), which may have a significant impact on how patients will be mechanically ventilated in the future (19). Macroscopic complexity in physiological variables, such as mechanical forces of tidal volume or blood pressure acting on cells (20), can regulate normal cell function.…”