Phospholipase A₂ in experimental allergic bronchitis: A lesson from mouse and rat models

Background: Phospholipases A₂ (PLA₂) hydrolyzes phospholipids, initiating the production of inflammatory lipid mediators. We have previously shown that in rats, sPLA₂ and cPLA₂ play opposing roles in the pathophysiology of ovalbumin (OVA)- induced experimental allergic bronchitis (OVA-EAB), an asthma model: Upon disease induction sPLA₂ expression and production of the broncho-constricting CysLTs are elevated, whereas cPLA₂ expression and the broncho-dilating PGE₂ production are suppressed. These were reversed upon disease amelioration by treatment with an sPLA₂ inhibitor. However, studies in mice reported the involvement of both sPLA₂ and cPLA₂ in EAB induction. Objectives: To examine the relevance of mouse and rat models to understanding asthma pathophysiology. Methods: OVA-EAB was induced in mice using the same methodology applied in rats. Disease and biochemical markers in mice were compared with those in rats. Results: As in rats, EAB in mice was associated with increased mRNA of sPLA₂, specifically sPLA₂gX, in the lungs, and production of the broncho-constricting eicosanoids CysLTs, PGD₂ and TBX₂ in bronchoalveolar lavage (BAL). In contrast, EAB in mice was associated also with elevated cPLA₂ mRNA and PGE₂ production. Yet, treatment with an sPLA₂ inhibitor ameliorated the EAB concomitantly with reverting the expression of both cPLA₂ and sPLA₂, and eicosanoid production. Conclusions: In both mice and rats sPLA₂ is pivotal in OVA-induced EAB. Yet, amelioration of asthma markers in mouse models, and human tissues, was observed also upon cPLA₂ inhibition. It is plausible that airway conditions, involving multiple cell types and organs, require the combined action of more than one, essential, PLA₂s.