P110 Gamma/Delta Double-Deficiency Induces Eosinophilia And Ige Production But Protects From Ova-Induced Airway Inflammation

The catalytical isoforms p110 gamma and p110 delta of phosphatidylinositide 3-kinase. (PI3K gamma) and PI3K delta play an important role in the pathogenesis of asthma. Two key elements in allergic asthma are increased levels of eosinophils and IgE. Dual pharmacological inhibition of p110 gamma and p110 delta reduces asthma-associated eosinophilic lung infiltration and ameliorates disease symptoms, whereas the absence of enzymatic activity in p110 gamma(KO)delta(D910)A mice increases IgE and basal eosinophil counts. This suggests that long-term inhibition of p110 gamma and p110d might exacerbate asthma. Here, we analysed mice genetically deficient for both catalytical subunits (p110 gamma/delta(-/-)) and determined basal IgE and eosinophil levels and the immune response to ovalbumin-induced asthma. Serum concentrations of IgE, IL-5 and eosinophil numbers were significantly increased in p110 gamma/delta(-/-) mice compared to single knock-out and wildtype mice. However, p110 gamma/delta(-/-) mice were protected against OVA-induced infiltration of eosinophils, neutrophils, T and B cells into lung tissue and bronchoal-veolar space. Moreover, p110 gamma/delta(-/-) mice, but not single knock-out mice, showed a reduced bronchial hyperresponsiveness. We conclude that increased levels of eosinophils and IgE in p110 gamma/delta(-/-) mice do not abolish the protective effect of p110 gamma/delta-deficiency against OVA-induced allergic airway inflammation.