Relationship between levels of secreted phospholipase A₂ groups IIA and X in the airways and asthma severity.
Background Secreted phospholipase A(2) (sPLA(2) ) may be important mediators of asthma, but the specific sPLA(2) s involved in asthma are not known. Objective To evaluate sPLA(2) group IIA, V, and X proteins (sPLA(2) -IIA, sPLA(2) -V, and sPLA(2) -X) in bronchoalveolar lavage (BAL) fluid, BAL cells, and airway epithelial cells of subjects with and without asthma, and examine the relationship between the levels of specific sPLA(2) enzymes and airway inflammation, asthma severity, and lung function. Methods The expression of sPLA(2) -IIA, sPLA(2) -V, and sPLA(2) -X in BAL cells and epithelial brushings was assessed by qPCR. The levels of these sPLA(2) proteins and sPLA(2) activity with and without group II and group X-specific inhibitors were measured in BAL fluid from 18 controls and 39 asthmatics. Results The airway epithelium expressed sPLA(2) -X at higher levels than either sPLA(2) -IIA or sPLA(2) -V, whereas BAL cells expressed sPLA(2) -IIA and sPLA(2) -X at similar levels. The majority of sPLA(2) activity in BAL fluid was attributed to either sPLA(2) -IIA or sPLA(2) -X. After 10-fold concentration of BAL fluid, the levels of sPLA(2) -X normalized to total protein were increased in asthma and were associated with lung function, the concentration of induced sputum neutrophils, and prostaglandin E(2) . The levels of sPLA(2) -IIA were elevated in asthma when normalized to total protein, but were not related to lung function, markers of airway inflammation or eicosanoid formation. Conclusions and Clinical Relevance These data indicate that sPLA(2) -IIA and sPLA(2) -X are the major sPLA(2) s in human airways, and suggest a link between the levels of sPLA(2) -X in the airways and several features of asthma.
Department of Medicine, Divisions of Pulmonary and Critical Care, University of Washington, Seattle, WA 98195, USA. tealh@u.washington.edu
T S
TS
Hallstrand
Y
Y
Lai
Z
Z
Ni
R C
RC
Oslund
W R
WR
Henderson
M H
MH
Gelb
S E
SE
Wenzel
D000328:Adult; D001249:Asthma / Q000201:enzymology* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D054501:Group II Phospholipases A2 / Q000378:metabolism*; D054509:Group X Phospholipases A2 / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020545:Respiratory Mucosa / Q000378:metabolism; D012137:Respiratory System / Q000201:enzymology* / Q000276:immunology; D012141:Respiratory Tract Infections / Q000201:enzymology / Q000276:immunology
D054501:Group II Phospholipases A2; D054509:Group X Phospholipases A2
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