Division of Pulmonary and Critical Care, University of Washington, Box 356522, 1959 NE Pacific Street, Seattle, WA 98195, USA.
Pulm Pharmacol Ther. 2012 Dec;25(6):432-7. doi: 10.1016/j.pupt.2012.02.004.
Alterations in the airway epithelium have been associated with the development of asthma in elite athletes and in subjects that are susceptible to exercise-induced bronchoconstriction (EIB). The syndrome of EIB refers to acute airflow obstruction that is triggered by a period of physical exertion. Asthmatics who are susceptible to EIB have increased levels of cysteinyl leukotrienes (CysLTs, i.e., LTs C₄, D₄, and E₄) in induced sputum and exhaled breath condensate, and greater shedding of epithelial cells into the airway lumen. Exercise challenge in individuals susceptible to this disorder initiates a sustained increase in CysLTs in the airways, and secreted mucin release and smooth muscle constriction, which may be mediated in part through activation of sensory nerves. We have identified a secreted phospholipase A₂ (sPLA₂) with increased levels in the airways of patients with EIB called sPLA₂ group X(sPLA₂-X).We have found that sPLA₂-X is strongly expressed in the airway epithelium in asthma. Further,we discovered that transglutaminase 2 (TGM2) is expressed at increased levels in asthma and serves asa regulator of sPLA₂-X. Finally, we demonstrated that sPLA₂-X acts on target cells such as eosinophils to initiate cellular eicosanoid synthesis. Collectively, these studies identify a novel mechanism linking the airway epithelium to the production of inflammatory eicosanoids by leukocytes.
气道上皮细胞的改变与精英运动员和易发生运动性支气管收缩（EIB）的受试者的哮喘发展有关。EIB 综合征是指由体力活动引发的急性气流阻塞。易发生 EIB 的哮喘患者在诱导痰和呼出气冷凝物中半胱氨酰白三烯（CysLTs，即 LTC4、D4 和 E4）水平升高，上皮细胞更多地脱落到气道腔中。易患这种疾病的个体进行运动挑战会引发气道中 CysLTs 的持续增加，以及分泌的粘蛋白释放和平滑肌收缩，这可能部分通过激活感觉神经来介导。我们已经鉴定出一种在 EIB 患者的气道中水平升高的分泌型磷脂酶 A₂（sPLA₂），称为 sPLA₂-X。我们发现 sPLA₂-X 在哮喘的气道上皮细胞中强烈表达。此外，我们发现转谷氨酰胺酶 2（TGM2）在哮喘中表达水平增加，并作为 sPLA₂-X 的调节剂。最后，我们证明 sPLA₂-X 作用于靶细胞，如嗜酸性粒细胞，以启动细胞类二十烷酸的合成。总之，这些研究确定了一种将气道上皮与白细胞产生炎症类二十烷酸联系起来的新机制。
