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Secreted Phospholipase A₂ Group X Overexpression in Asthma and Bronchial Hyperresponsiveness

Departments of ¹ Medicine, ² Pathology, and ³ Chemistry, University of Washington, Seattle, Washington

Correspondence and requests for reprints should be addressed to Teal S. Hallstrand, M.D., M.P.H., Division of Pulmonary and Critical Care, Department of Medicine, University of Washington, Box 356522, Seattle, WA 98195. E-mail: tealh{at}u.washington.edu

Rationale: Secreted phospholipase A₂ enzymes (sPLA₂s) play key regulatory roles in the biosynthesis of eicosanoids, such as the cysteinyl leukotrienes, 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 patients with asthma, and to determine if these enzymes may play a role in the generation of eicosanoids in exercise-induced bronchoconstriction.

Methods: Induced sputum samples were obtained from subjects with asthma with exercise-induced bronchoconstriction and nonasthmatic control subjects at baseline, and on a separate day 30 minutes after exercise challenge. The expression of the PLA₂s in induced sputum cells and supernatant was determined by quantitative polymerase chain reaction, immunocytochemistry, and Western blot.

Measurements and Main Results: The sPLA₂s expressed at the highest levels in airway cells of subjects with asthma 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, whereas the levels were lower and unchanged after challenge in nonasthmatic control subjects.

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 • macrophage

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Secreted phospholipase A2 (sPLA2) enzymes have recently emerged as critical regulators of eicosanoid synthesis, but the specific sPLA2 enzymes expressed in human airways and the role of these enzymes in asthma pathogenesis are not known. What This Study Adds to the Field Group X sPLA2 is overexpressed in airway epithelial cells and bronchial macrophages of subjects with asthma, and released in response to exercise challenge, a stimulus that causes dysregulated eicosanoid synthesis.

 

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