Effect of secreted phospholipase A ₂ group IID, IIE, and IIF-deficiency on allergen-driven asthma phenotype

Rationale : Exaggerated inflammation and remodeling in the airways of patients with asthma occurs through complex Th2 cytokine, chemokine, growth factor, and eicosanoid interactions. The mammalian genome encodes 10 secreted phospholipase A 2 (sPLA 2 )s. The role of these sPLA 2 s in eicosanoid biosynthesis has been unclear. We have found that mice that lack groups X and V (respectively Henderson, W.R., Jr. et al. J Exp Med 2007; 204:865-77 and Henderson, W.R., Jr. et al. PLOS ONE 2013; DOI:10.1371/journal.pone.0056172) sPLA 2 s show reduction in Th2 cytokine-driven airway hyperresponsiveness (AHR) and inflammation. Data are lacking regarding the effect on asthma phenotype of the group IID, IIE, and IIF sPLA 2 enzymes that share a common three-dimensional structure with group V and X sPLA 2 s. Study Aim : Determine the role of group IID, IIE, and IIF sPLA 2 s in the mediation of airway inflammation and AHR in an ovalbumin (OVA)-induced mouse asthma model. Results : Airway infiltration by eosinophils (by morphometric analysis) and lung IL-5 release (by qPCR) were decreased in OVA-treated sPLA 2 -IID and IIE knockout (KO) mice compared to wildtype (WT) controls. These parameters of the asthma phenotype were unaffected by sPLA 2 -IIF deficiency. OVA-induced airway mucus metaplasia (by alcian blue histopathology) and AHR (by invasive plethysmography to inhaled methacholine) were not different between WT and sPLA 2 -IID, IIE, and IIF KOs. Conclusions : These results direct attention to the potential role of group IID and IIE sPLA 2 s in IL-5-mediated trafficking of eosinophils to the airways in allergen-driven asthma. Research Funding Source : National Institutes of Health grant HL36235.