Published ahead of print on September 27, 2007, doi:10.1164/rccm.200707-1088OC Am. J. Respir. Crit. Care Med., Volume 176, Number 11, December 2007, 1072-1078 A more recent version of this article appeared on December 1, 2007
Submitted on July 23, 2007 Secreted Phospholipase A2 Group X Overexpression in Asthma and Bronchial HyperresponsivenessTeal S Hallstrand1*,1 Department of Medicine, University of Washington, Seattle, WA, USA, 2 Department of Pathology, University of Washington, Seattle, WA, USA, 3 Department of Chemistry, University of Washington, Seattle, WA, USA * To whom correspondence should be addressed. E-mail: tealh{at}u.washington.edu.
Rationale: Secreted PLA2s (sPLA2)s play key regulatory roles in the biosynthesis of eicosanoids such as the cysteinyl leukotrienes (CysLT)s, but the role of these enzymes in the pathogenesis of asthma is not known. Objectives: To establish if sPLA2s are overexpressed in the airways of asthmatics, and determine if these enzymes may play a role in the generation of eicosanoids in exercise-induced bronchoconstriction (EIB). Methods: Induced sputum samples were obtained from asthmatic subjects with EIB, and non-asthmatic controls at baseline, and on a separate day 30 min after exercise challenge. The expression of the PLA2s in induced sputum cells and supernatant was determined by quantitative PCR, immunocytochemistry, and Western blot. Main Results: The sPLA2s expressed at the highest levels in airway cells of asthmatics were groups X and XIIA. Group X sPLA2 (sPLA2-X) was differentially overexpressed in asthma and localized to airway epithelial cells and bronchial macrophages. The gene expression, immunostaining in airway epithelial cells and bronchial macrophages, and the level of the extracellular sPLA2-X protein in the airways increased in response to exercise challenge in the asthma group, while the levels were lower and unchanged following challenge in non-asthmatic controls. Conclusions: Increased expression of sPLA2-X may play a key role in the dysregulated eicosanoid synthesis in asthma. Key words: Asthma, Eicosanoid, Epithelial Cell, Leukotriene, and Macrophage
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