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

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.

• Authors: William R Henderson Jr, Xin Ye, Ying Lai, Zhanglin Ni, James G Bollinger, Ying-Tzang Tien, Emil Y Chi, Michael H Gelb
• Journal: PloS one (PLoS One) Vol. 8 Issue 2 Pg. e56172 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23451035 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Ovalbumin
• Group V Phospholipases A2
• Group X Phospholipases A2

Topics

• Animals
• Asthma (enzymology, genetics, immunology)
• CD4-Positive T-Lymphocytes (metabolism)
• Disease Models, Animal
• Group V Phospholipases A2 (genetics, metabolism)
• Group X Phospholipases A2 (genetics, metabolism)
• Immunohistochemistry
• Mice
• Mice, Knockout
• Ovalbumin (immunology)
• Polymerase Chain Reaction
• Th2 Cells (metabolism)