Secreted Phospholipase A2 Group X Acts as an Adjuvant for Type 2 Inflammation, Leading to an Allergen-Specific Immune Response in the Lung

Secreted phospholipase A(2) (sPLA(2)) enzymes release free fatty acids, including arachidonic acid, and generate lysophospholipids from phospholipids, including membrane phospholipids from cells and bacteria and surfactant phospholipids. We have shown that an endogenous enzyme sPLA(2) group X (sPLA(2)-X) is elevated in the airways of asthmatics and that mice lacking the sPLA(2)-X gene (Pla2g10) display attenuated airway hyperresponsiveness, innate and adaptive immune responses, and type 2 cytokine production in a model of airway sensitization and challenge using a complete allergen that induces endogenous adjuvant activity. This complete allergen also induces the expression of sPLA(2)-X/Pla2g10. In the periphery, an sPLA(2) found in bee venom (bee venom PLA 2 ) administered with the incomplete Ag OVA leads to an Ag-specific immune response. In this study, we demonstrate that both bee venom PLA(2) and murine sPLA(2) -X have adjuvant activity, leading to a type 2 immune response in the lung with features of airway hyperresponsiveness and Ag-specific type 2 airway inflammation following peripheral sensitization and subsequent airway challenge with OVA. Further, the adjuvant effects of sPLA(2)-X that result in the type 2-biased OVA-specific adaptive immune response in the lung were dependent upon the catalytic activity of the enzyme, as a catalytically inactive mutant form of sPLA(2)-X does not elicit the adaptive component of the immune response, although other components of the immune response were induced by the inactive enzyme, suggesting receptor-mediated effects. Our results demonstrate that exogenous and endogenous sPLA(2) s play an important role in peripheral sensitization, resulting in airway responses to inhaled Ags.