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Exercise-Induced Alterations in Phospholipid Hydrolysis, Airway Surfactant and Eicosanoids and their Role in Airway Hyperresponsiveness in Asthma
American Journal of Physiology-Lung Cellular and Molecular Physiology ( IF 4.9 ) Pub Date : 2021-02-03 , DOI: 10.1152/ajplung.00546.2020
Ryan C Murphy 1, 2 , Ying Lai 1, 2 , James D Nolin 1, 2 , Robier A Aguillon Prada 3, 4 , Arindam Chakrabarti 3, 4 , Michael V Novotny 3, 4 , Michael C Seeds 5 , William A Altemeier 1, 2 , Michael H Gelb 6, 7 , Robert Duncan Hite 8 , Teal S Hallstrand 1, 2
Affiliation  

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.

中文翻译:

运动引起的磷脂水解、气道表面活性剂和类花生酸的改变及其在哮喘气道高反应性中的作用

以运动诱发的支气管收缩 (EIB) 形式驱动内源性气道高反应性 (AHR) 的机制尚不完全清楚。我们检查了与 AHR 严重程度和运动挑战引起的变化相关的气道磷脂水解、表面活性剂降解和脂质介质释放的变化。在哮喘受试者运动挑战前后获得配对诱导痰液(n=18)和支气管肺泡灌洗液(BAL)液(n=11)。分析样品的磷脂结构、表面活性剂功能以及类花生酸和分泌的磷脂酶 A 2第 10 组 (sPLA 2 -X) 的水平。原代上皮细胞培养模型用于模拟渗透应力对 sPLA 2的影响-X。运动挑战导致所有患者痰液样本中的表面活性剂降解、磷脂酶活性和类花生酸产生增加。EIB 受试者在 BAL 液中具有更高水平的表面活性剂降解和磷脂酶活性。较高的半胱氨酰白三烯 (CysLTs) 和前列腺素 D 2 (PGD 2 ) 基础痰水平与直接 AHR 相关,并且 CysLTs 和 PGD 2水平的运动后和绝对变化都与 EIB 严重程度相关。表面活性剂功能要么在基线时异常,要么在运动挑战后变得异常。痰中 sPLA 2 -X 的基线水平和 sPLA 2量的绝对变化-X 与运动与 EIB 严重程度呈正相关。离体渗透应力导致水的运动和sPLA 2 -X 释放到顶端表面。总之,运动挑战促进了哮喘中磷脂结构和类花生酸释放的变化,提供了两种促进支气管收缩的机制,特别是在具有较高基础水平磷脂转换的 EIB 个体中。
更新日期:2021-02-04
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