Crucial role of group IIA phospholipase A(2) in oleic acid-induced acute lung injury in rabbits

Group IIA secretory phospholipase A(2) (sPLA(2)) has been implicated in a v ariety of inflammatory diseases including acute lung injury (ALI); however, the role of sPLA(2) in this disorder remains unclear. The aim of the prese nt investigation was to examine the role of this enzyme in a model of ALI i nduced by oleic acid (OA) in rabbits by testing human group IIA phospholipa se A(2) (PLA(2)) inhibitor, S-5920/LY315920Na. Experimental groups consiste d of a saline control group (n = 8), an OA control group (n = 10) infused i ntravenously with OA (0.1 ml/kg/h for 2 h), and three groups given OA + S-5 920/LY315920Na (three different doses, n = 8, respectively). Infusion of OA provoked pulmonary hemorrhage and edema formation, protein leakage, and ma ssive neutrophil infiltration, resulting in severe hypoxemia and impaired l ung compliance. PLA(2) activity was detected in the bronchoalveolar lavage fluid (BALF), but not plasma, which correlated well with severity of lung i njury in this model. Pretreatment with S-5920/LY315920Na diminished the OA- induced PLA(2) activity in the BALF and dose-dependently attenuated the pre viously described lung injury induced by OA, accompanied by protection agai nst lung surfactant degradation and production of thromboxane A(2) (TXA(2)) and leukotriene B-4 (LTB4). S-5920/LY315920Na also inhibited the OA-induce d production of interleukin-8 (IL-8), both in plasma and BALF. Thus, sPLA(2 ) appears to play a key role in OA-induced lung injury, suggesting that the group IIA PLA(2) inhibitor may be a promising agent for patients with acut e respiratory distress syndrome (ARDS).