• William R Henderson, Xin Ye, Ying Lai, Zhanglin Ni, James G Bollinger, Ying-Tzang Tien, Emil Y Chi, and Michael H Gelb.
• Center for Allergy and Inflammation, UW Medicine at South Lake Union, Department of Medicine, University of Washington, Seattle, Washington, United States of America. wrhchem@u.washington.edu
• Plos One. 2013 Jan 1;8(2):e56172.

BackgroundPrevious 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 FindingsThe 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.ConclusionsThis 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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