Group IIA secretory
phospholipase A(2) (
sPLA(2)) has been implicated in a variety of inflammatory diseases including
acute lung injury (ALI); however, the role of
sPLA(2) in this disorder remains unclear. The aim of the present investigation was to examine the role of this
enzyme in a model of ALI induced by
oleic acid (OA) in rabbits by testing human group IIA
phospholipase A(2) (PLA(2)) inhibitor,
S-5920/LY315920Na. Experimental groups consisted of a saline control group (n = 8), an OA control group (n = 10) infused intravenously with OA (0.1 ml/kg/h for 2 h), and three groups given OA +
S-5920/LY315920Na (three different doses, n = 8, respectively). Infusion of OA provoked pulmonary
hemorrhage and
edema formation,
protein leakage, and massive neutrophil infiltration, resulting in severe
hypoxemia and impaired lung compliance. PLA(2) activity was detected in the bronchoalveolar lavage fluid (BALF), but not plasma, which correlated well with severity of
lung injury in this model. Pretreatment with
S-5920/LY315920Na diminished the OA-induced PLA(2) activity in the BALF and dose-dependently attenuated the previously described
lung injury induced by OA, accompanied by protection against lung
surfactant degradation and production of
thromboxane A(2) (TXA(2)) and
leukotriene B(4) (LTB(4)).
S-5920/LY315920Na also inhibited the OA-induced 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
acute respiratory distress syndrome (ARDS).