Document Detail

Epithelial regulation of eicosanoid production in asthma.
MedLine Citation:
PMID:  23323271     Owner:  NLM     Status:  MEDLINE    
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.
Teal S Hallstrand; Ying Lai; William R Henderson; William A Altemeier; Michael H Gelb
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Pulmonary pharmacology & therapeutics     Volume:  25     ISSN:  1522-9629     ISO Abbreviation:  Pulm Pharmacol Ther     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2013-01-15     Completed Date:  2013-05-16     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  9715279     Medline TA:  Pulm Pharmacol Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  432-7     Citation Subset:  IM    
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MeSH Terms
Asthma / physiopathology*
Asthma, Exercise-Induced / physiopathology*
Cysteine / metabolism
Eicosanoids / metabolism*
Epithelial Cells / metabolism
Exercise Test
Group X Phospholipases A2 / metabolism
Leukocytes / metabolism
Leukotrienes / metabolism
Phospholipases A2, Secretory / metabolism
Grant Support
Reg. No./Substance:
0/Eicosanoids; 0/Leukotrienes; 0/cysteinyl-leukotriene; EC X Phospholipases A2; EC A2, Secretory; K848JZ4886/Cysteine

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