Cytosolic Phospholipase A2 Inhibition Attenuates Ischemia-Reperfusion Injury in an Isolated Rat Lung Model
| Autor: | Hideki Akamatsu, Katsuo Kojima, Makoto Sunamori, Hiroyuki Tanaka, Yury A. Bellido-Reyes, Hirokuni Arai |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Neutrophils Thromboxane Arachidonic Acids Platelet Membrane Glycoproteins In Vitro Techniques Lung injury Pharmacology Phospholipases A Receptors G-Protein-Coupled Group VI Phospholipases A2 Rats Sprague-Dawley chemistry.chemical_compound Phospholipase A2 medicine Animals Phosphorylation Lung Arachidonyl trifluoromethyl ketone Transplantation Phospholipase A Neutrophil extravasation biology Group IV Phospholipases A2 respiratory system medicine.disease Rats Disease Models Animal Phospholipases A2 chemistry Reperfusion Injury Immunology biology.protein Eicosanoids Arachidonic acid Reperfusion injury Lung Transplantation |
| Zdroj: | Transplantation. 81:1700-1707 |
| ISSN: | 0041-1337 |
| DOI: | 10.1097/01.tp.0000226065.82066.21 |
| Popis: | Background. Arachidonic acid metabolites and platelet-activating factor (PAF) are potentially involved in ischemia-reperfusion (IR) lung injury. A key enzyme regulating their metabolism is cytosolic phospholipase A 2 (cPLA 2 ). Arachidonyl trifluoromethyl ketone (AACOCF 3 ) is reported to be a potent cPLA 2 inhibitor. In the present study, we hypothesized that pharmacological inhibition of cPLA 2 might ameliorate IR lung injury. Methods. To test the hypothesis, we examined the effects of AACOCF 3 in an isolated rat lung model. Three groups were defined (n=6, each): in the vehicle group, lungs were perfused for 2 hours without an ischemic period. In the ischemic groups, 20 mg/kg of AACOCF 3 (AACOCF 3 group) or saline (control group) was i.v. administered 15 min before lung harvest. Lungs were flushed with LPD solution, cold-stored 18 hours, and reperfused for 2 hours. Results. IR increased cPLA 2 activity mainly via alveolar macrophages, sPLA 2 activity, thromboxane and leukotriene formation, and the expression of PAF receptor, whereas AACOCF3 treatment significantly reduced all of these. Compared to the vehicle group, the wet-to-dry ratio, proteins in BAL, and MPO activity increased significantly by twofold, fourfold, and threefold, respectively. Furthermore, the PO 2 dropped from 615.7±31.2 to 452.1±30.9 mmHg at the end of reperfusion (P |
| Databáze: | OpenAIRE |
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