PT  - JOURNAL ARTICLE
AU  - William Henderson
AU  - James Bollinger
AU  - Jun Xue
AU  - Ying-Tzang Tien
AU  - Michael Gelb
TI  - Effect of secreted phospholipase A<sub>2</sub> group IID, IIE, and IIF-deficiency on allergen-driven asthma phenotype
DP  - 2013 Sep 01
TA  - European Respiratory Journal
PG  - P1567
VI  - 42
IP  - Suppl 57
4099  - http://erj.ersjournals.com/content/42/Suppl_57/P1567.short
4100  - http://erj.ersjournals.com/content/42/Suppl_57/P1567.full
SO  - Eur Respir J2013 Sep 01; 42
AB  - 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 A2 (sPLA2)s. The role of these sPLA2s 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) sPLA2s 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 sPLA2 enzymes that share a common three-dimensional structure with group V and X sPLA2s.Study Aim: Determine the role of group IID, IIE, and IIF sPLA2s 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 sPLA2-IID and IIE knockout (KO) mice compared to wildtype (WT) controls. These parameters of the asthma phenotype were unaffected by sPLA2-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 sPLA2-IID, IIE, and IIF KOs.Conclusions: These results direct attention to the potential role of group IID and IIE sPLA2s in IL-5-mediated trafficking of eosinophils to the airways in allergen-driven asthma.Research Funding Source: National Institutes of Health grant HL36235.