title: Epithelial regulation of eicosanoid production in asthma.
abstract: 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.
authors: Division of Pulmonary and Critical Care, University of Washington, Box 356522, 1959 NE Pacific Street, Seattle, WA 98195, USA. tealh@u.washington.edu
authors: Teal S
authors: TS
authors: Hallstrand
authors: Ying
authors: Y
authors: Lai
authors: William R
authors: WR
authors: Henderson
authors: William A
authors: WA
authors: Altemeier
authors: Michael H
authors: MH
authors: Gelb
mesh_terms: D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D001250:Asthma, Exercise-Induced / Q000503:physiopathology*; D003545:Cysteine / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005080:Exercise Test; D054509:Group X Phospholipases A2 / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D054497:Phospholipases A2, Secretory / Q000378:metabolism
chemical_list: D015777:Eicosanoids; D015289:Leukotrienes; C112381:cysteinyl-leukotriene; D054509:Group X Phospholipases A2; D054497:Phospholipases A2, Secretory; D003545:Cysteine