Exercise-Induced Alterations in Phospholipid Hydrolysis, Airway Surfactant and Eicosanoids and their Role in Airway Hyperresponsiveness in Asthma

The mechanisms responsible for driving endogenous airway hyperresponsiveness (AHR) in the form of exercise-induced bronchoconstriction (EIB) are not fully understood. We examined alterations in airway phospholipid hydrolysis, surfactant degradation, and lipid mediator release in relation to AHR severity and changes induced by exercise challenge. Paired induced sputum (n=18) and bronchoalveolar lavage (BAL) fluid (n=11) were obtained before and after exercise challenge in asthmatic subjects. Samples were analyzed for phospholipid structure, surfactant function and levels of eicosanoid and secreted phospholipase A2 group 10 (sPLA2-X). A primary epithelial cell culture model was used to model effects of osmotic stress on sPLA2-X. Exercise challenge resulted in increased surfactant degradation, phospholipase activity, and eicosanoid production in sputum samples of all patients. Subjects with EIB had higher levels of surfactant degradation and phospholipase activity in BAL fluid. Higher basal sputum levels of cysteinyl leukotrienes (CysLTs) and prostaglandin D2 (PGD2) were associated with direct AHR and both the post-exercise and absolute change in CysLTs and PGD2 levels were associated with EIB severity. Surfactant function was either abnormal at baseline or became abnormal after exercise challenge. Baseline levels of sPLA2-X in sputum and the absolute change in amount of sPLA2-X with exercise were positively correlated with EIB severity. Osmotic stress ex vivo resulted in movement of water and release of sPLA2-X to the apical surface. In summary, exercise challenge promotes changes in phospholipid structure and eicosanoid release in asthma, providing two mechanisms that promote bronchoconstriction, particularly in individuals with EIB who have higher basal levels phospholipid turnover.

Calculation of the magnetic resonance isotropy tensors of the nucleus of POPC phospholipid bilayers in a cell membrane

Importance of membrane phospholipids and their various applications in various sciences and industries including chemistry and biochemistry, chemical sensors and treatment of diseases and effective delivery of drugs and materials through cellular membrane is clear. Investigation of the NMR parameters including isotropy of the isotropic value (σiso), anisotropy chemical shift (σaniso), reduced anisotropy (δ), asymmetric parameter (η) of the anisotropy parameter (Δσ) and skew parameter (Ҡ) enables the recognition of target active centers. Phospholipid structure was optimized using calculation of molecular mechanics and quantum mechanics. Then, using ab initio calculations, factors of NMR chemical isotropy tensor were calculated for membrane phospholipids. According to results, it was found out that carbon no. 2 bonded to nitrogen and after that, no. 32 carbon atom bonded to the oxygen have most contribution to the dynamics movements of phospholipid in membrane. It can be concluded that high electronegativity of the nitrogen and oxygen plays an important role in sensitivity of the phospholipid carbons. Increased number of electronegative agents in the phospholipid results in better control of the dynamic role of the membrane. Evaluation of the NMR parameters of phospholipid structure led to recognition of the active centers and owing to the mutual effect of these centers, transfer and exchange in these active sites and if agents similar to the human’s genetic structure are taken into account for transfer and exchange, they can be very useful and rapid transmitters for delivery of drugs to the target cells.