Crucial role of group IIA phospholipase A2 in oleic acid-induced acute lung injury in rabbits

Shingo Furue, Kenji Kuwabara, Katsuya Mikawa, Kahoru Nishina, Makoto Shiga, Nobuhiro Maekawa, Masahiko Ueno, Yukiko Chikazawa, Takashi Ono, Yozo Hori, Akihiro Matsukawa, Masaru Yoshinaga, Hidefumi Obara

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Abstract

Group IIA secretory phospholipase A2 (sPLA2) has been implicated in a variety of inflammatory diseases including acute lung injury (ALI); however, the role of sPLA2 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 A2 (PLA2) 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. PLA2 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 PLA2 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 A2 (TXA2) and leukotriene B4 (LTB4). S-5920/LY315920Na also inhibited the OA-induced production of interleukin-8 (IL-8), both in plasma and BALF. Thus, sPLA2 appears to play a key role in OA-induced lung injury, suggesting that the group IIA PLA2 inhibitor may be a promising agent for patients with acute respiratory distress syndrome (ARDS).

Original languageEnglish
Pages (from-to)1292-1302
Number of pages11
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume160
Issue number4
Publication statusPublished - 1999
Externally publishedYes

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ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Furue, S., Kuwabara, K., Mikawa, K., Nishina, K., Shiga, M., Maekawa, N., Ueno, M., Chikazawa, Y., Ono, T., Hori, Y., Matsukawa, A., Yoshinaga, M., & Obara, H. (1999). Crucial role of group IIA phospholipase A2 in oleic acid-induced acute lung injury in rabbits. American Journal of Respiratory and Critical Care Medicine, 160(4), 1292-1302.