Crucial role of group IIA phospholipase A(2) in oleic acid-induced acute lung injury in rabbits
| Autor: | Nobuhiro Maekawa, Makoto Shiga, Kahoru Nishina, Masaru Yoshinaga, Hidefumi Obara, Yozo Hori, Kenji Kuwabara, Yukiko Chikazawa, Katsuya Mikawa, Masahiko Ueno, Takashi Ono, Shingo Furue, Akihiro Matsukawa |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Pulmonary and Respiratory Medicine
Male ARDS Indoles Thromboxane Pulmonary Edema Lung injury Pulmonary compliance Pharmacology Acetates Critical Care and Intensive Care Medicine Group II Phospholipases A2 Leukotriene B4 Phospholipases A Capillary Permeability Thromboxane A2 Phospholipase A2 Medicine Animals Enzyme Inhibitors Lung Lung Compliance Phospholipids Phospholipase A Respiratory Distress Syndrome biology medicine.diagnostic_test Dose-Response Relationship Drug business.industry Respiratory disease Interleukin-8 respiratory system medicine.disease Keto Acids respiratory tract diseases Oxygen Bronchoalveolar lavage Immunology Extravascular Lung Water biology.protein Rabbits business Bronchoalveolar Lavage Fluid Oleic Acid |
| Zdroj: | American journal of respiratory and critical care medicine. 160(4) |
| ISSN: | 1073-449X |
| Popis: | 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). |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|