PLoS One. 2013; 8(2): e56172.
Published online 2013 February 25. doi: 10.1371/journal.pone.0056172
PMCID: PMC3581544
William R. Henderson Jr,1,* Xin Ye,1,¤ Ying Lai,2 Zhanglin Ni,2 James G. Bollinger,2 Ying-Tzang Tien,3 Emil Y. Chi,3and Michael H. Gelb2,4,*
Christian Taube, Editor
Abstract
Background
Previous work has shown that disruption of the gene for group X secreted phospholipase A2 (sPLA2-X) markedly diminishes airway hyperresponsiveness and remodeling in a mouse asthma model. With the large number of additional sPLA2s in the mammalian genome, the involvement of other sPLA2s in the asthma model is possible – in particular, the group V sPLA2 (sPLA2-V) that like sPLA2-X is highly active at hydrolyzing membranes of mammalian cells.
Methodology and Principal Findings
The allergen-driven asthma phenotype was significantly reduced in sPLA2-V-deficient mice but to a lesser extent than observed previously in sPLA2-X-deficient mice. The most striking difference observed between the sPLA2-V and sPLA2-X knockouts was the significant impairment of the primary immune response to the allergen ovalbumin (OVA) in the sPLA2-V−/− mice. The impairment in eicosanoid generation and dendritic cell activation in sPLA2-V−/− mice diminishes Th2 cytokine responses in the airways.
Conclusions
This paper illustrates the diverse roles of sPLA2s in the immunopathogenesis of the asthma phenotype and directs attention to developing specific inhibitors of sPLA2-V as a potential new therapy to treat asthma and other allergic disorders.
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