Am. J. Respir. Crit. Care Med., Volume 160, Number 4, October 1999, 1292-1302

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, and HIDEFUMI OBARA

Department of Anesthesiology, Kobe University School of Medicine, Kobe, Japan; Department of Pathology, Kumamoto University School of Medicine, Kumamoto, Japan; and Discovery Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan

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).

This article has been cited by other articles:

				S. Lin, J. Walker, L. Xu, D. Gozal, and J. Yu Respiratory: Behaviours of pulmonary sensory receptors during development of acute lung injury in the rabbit Exp Physiol, July 1, 2007; 92(4): 749 - 755. [Abstract] [Full Text] [PDF]

				I. B. Copland, D. Reynaud, C. Pace-Asciak, and M. Post Mechanotransduction of stretch-induced prostanoid release by fetal lung epithelial cells Am J Physiol Lung Cell Mol Physiol, September 1, 2006; 291(3): L487 - L495. [Abstract] [Full Text] [PDF]

				L. L. Hill, D. L. Chen, J. Kozlowski, and D. P. Schuster Neutrophils and Neutrophil Products Do Not Mediate Pulmonary Hemodynamic Effects of Endotoxin on Oleic Acid-Induced Lung Injury Anesth. Analg., February 1, 2004; 98(2): 452 - 457. [Abstract] [Full Text] [PDF]

				M. de Perrot, M. Liu, T. K. Waddell, and S. Keshavjee Ischemia-Reperfusion-induced Lung Injury Am. J. Respir. Crit. Care Med., February 15, 2003; 167(4): 490 - 511. [Abstract] [Full Text] [PDF]

				K.-i. Higashino, Y. Yokota, T. Ono, S. Kamitani, H. Arita, and K. Hanasaki Identification of a Soluble Form Phospholipase A2 Receptor as a Circulating Endogenous Inhibitor for Secretory Phospholipase A2 J. Biol. Chem., April 12, 2002; 277(16): 13583 - 13588. [Abstract] [Full Text] [PDF]

				Y. Wu, M. Singer, F. Thouron, M. Alaoui-El-Azher, and L. Touqui Effect of surfactant on pulmonary expression of type IIA PLA2 in an animal model of acute lung injury Am J Physiol Lung Cell Mol Physiol, April 1, 2002; 282(4): L743 - L750. [Abstract] [Full Text] [PDF]

				D. P. Schuster, J. K. Kozlowski, T. McCarthy, J. Morrow, and A. Stephenson Effect of endotoxin on oleic acid lung injury does not depend on priming J Appl Physiol, November 1, 2001; 91(5): 2047 - 2054. [Abstract] [Full Text] [PDF]