Secreted phospholipase A2 group X overexpression in asthma and bronchial hyperresponsiveness.
BACKGROUND
Secreted phospholipase A(2) enzymes (sPLA(2)s) 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.


OBJECTIVE
To establish if sPLA(2)s 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 PLA(2)s in induced sputum cells and supernatant was determined by quantitative polymerase chain reaction, immunocytochemistry, and Western blot.


RESULTS
The sPLA(2)s expressed at the highest levels in airway cells of subjects with asthma were groups X and XIIA. Group X sPLA(2) (sPLA(2)-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 sPLA(2)-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 sPLA(2)-X may play a key role in the dysregulated eicosanoid synthesis in asthma.
Hallstrand
Teal S
TS
Division of Pulmonary and Critical Care, Department of Medicine, University of Washington, Box 356522, Seattle, WA 98195, USA. tealh@u.washington.edu
Chi
Emil Y
EY
Singer
Alan G
AG
Gelb
Michael H
MH
Henderson
William R
WR
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000201:enzymology* / Q000378:metabolism / Q000503:physiopathology; D001980:Bronchi / Q000201:enzymology; D016535:Bronchial Hyperreactivity / Q000201:enzymology* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D016084:Bronchoconstriction; D015331:Cohort Studies; D015777:Eicosanoids / Q000032:analysis; D004847:Epithelial Cells / Q000201:enzymology; D015444:Exercise; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D054497:Phospholipases A2, Secretory / Q000145:classification / Q000378:metabolism*; D012137:Respiratory System / Q000201:enzymology; D013183:Sputum / Q000737:chemistry / Q000166:cytology
D015777:Eicosanoids; D007527:Isoenzymes; D054497:Phospholipases A2, Secretory