Relationship between levels of secreted phospholipase A2 groups IIA and X in the airways and asthma severity

Authors


Correspondence:
Teal S. Hallstrand, Department of Medicine, Division of Pulmonary and Critical Care, University of Washington, Box 356522, Seattle, WA 98195, USA. E-mail: tealh@u.washington.edu

Abstract

Cite this as: T. S. Hallstrand, Y. Lai, Z. Ni, R. C. Oslund, W. R. Henderson Jr, M. H. Gelb and S. E. Wenzel, Clinical & Experimental Allergy, 2011 (41) 801–810.

Summary

Background Secreted phospholipase A2 (sPLA2) may be important mediators of asthma, but the specific sPLA2s involved in asthma are not known.

Objective To evaluate sPLA2 group IIA, V, and X proteins (sPLA2-IIA, sPLA2-V, and sPLA2-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 sPLA2 enzymes and airway inflammation, asthma severity, and lung function.

Methods The expression of sPLA2-IIA, sPLA2-V, and sPLA2-X in BAL cells and epithelial brushings was assessed by qPCR. The levels of these sPLA2 proteins and sPLA2 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 sPLA2-X at higher levels than either sPLA2-IIA or sPLA2-V, whereas BAL cells expressed sPLA2-IIA and sPLA2-X at similar levels. The majority of sPLA2 activity in BAL fluid was attributed to either sPLA2-IIA or sPLA2-X. After 10-fold concentration of BAL fluid, the levels of sPLA2-X normalized to total protein were increased in asthma and were associated with lung function, the concentration of induced sputum neutrophils, and prostaglandin E2. The levels of sPLA2-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 sPLA2-IIA and sPLA2-X are the major sPLA2s in human airways, and suggest a link between the levels of sPLA2-X in the airways and several features of asthma.

Ancillary