Phospholipase A(2) in Experimental Allergic Bronchitis: A Lesson from Mouse and Rat Models

BACKGROUND: Phospholipases A(2) (PLA(2)) hydrolyzes phospholipids, initiating the production of inflammatory lipid mediators. We have previously shown that in rats, sPLA(2) and cPLA(2) play opposing roles in the pathophysiology of ovalbumin (OVA)-induced experimental allergic bronchitis (OVA-EAB), an asthma model: Upon disease induction sPLA(2) expression and production of the broncho-constricting CysLTs are elevated, whereas cPLA(2) expression and the broncho-dilating PGE(2) production are suppressed. These were reversed upon disease amelioration by treatment with an sPLA(2) inhibitor. However, studies in mice reported the involvement of both sPLA(2) and cPLA(2) 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 sPLA(2), specifically sPLA(2)gX, in the lungs, and production of the broncho-constricting eicosanoids CysLTs, PGD(2) and TBX(2) in bronchoalveolar lavage (BAL). In contrast, EAB in mice was associated also with elevated cPLA(2) mRNA and PGE(2) production. Yet, treatment with an sPLA(2) inhibitor ameliorated the EAB concomitantly with reverting the expression of both cPLA(2) and sPLA(2), and eicosanoid production. CONCLUSIONS: In both mice and rats sPLA(2) is pivotal in OVA-induced EAB. Yet, amelioration of asthma markers in mouse models, and human tissues, was observed also upon cPLA(2) inhibition. It is plausible that airway conditions, involving multiple cell types and organs, require the combined action of more than one, essential, PLA(2)s.