Key role of group v secreted phospholipase A2 in Th2 cytokine and dendritic cell-driven airway hyperresponsiveness and remodeling

• Published in: PloS one 2013-02, Vol.8 (2), p.e56172-e56172
• Main Authors: Henderson, Jr, William R, Ye, Xin, Lai, Ying, Ni, Zhanglin, Bollinger, James G, Tien, Ying-Tzang, Chi, Emil Y, Gelb, Michael H
• Format: Article
• Language: English
• Subjects: Acids; Allergens; Allergies; Animals; Antigens; Asthma; Asthma - enzymology; Asthma - genetics; Asthma - immunology; Biology; Biosynthesis; CD4-Positive T-Lymphocytes - metabolism; Cell activation; Cytokines; Dendritic cells; Disease Models, Animal; Enzymes; Genomes; Group V Phospholipases A2 - genetics; Group V Phospholipases A2 - metabolism; Group X Phospholipases A2 - genetics; Group X Phospholipases A2 - metabolism; Immune response; Immune system; Immunohistochemistry; Immunopathogenesis; Impairment; Inflammation; Kinases; Lymphocytes T; Mammalian cells; Mammals; Medicine; Membranes; Mice; Mice, Knockout; Neutrophils; Ovalbumin; Ovalbumin - immunology; Phospholipase; Phospholipase A2; Polymerase Chain Reaction; Remodeling; Respiratory tract; Studies; Th2 Cells - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0056172

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. 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. 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.