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Effect of the Inhibition of Platelet Activating Factor on Oxidative Lung Injury Induced by Interleukin-$1\;{\alpha}$

Lee, Young-Man   (Department of Physiology, School of Medicine, Catholic University of Taegu-HyosungUU0013933  ); Park, Yoon-Yub   (Department of Physiology, School of Medicine, Catholic University of Taegu-HyosungUU0013933  );
  • 초록

    In order to know the pathogenesis of adult respiratory distress syndrome (ARDS) in association with the oxidative stress by neutrophils, the role of platelet activating factor (1-0-alkyl-2-acetyl-snglycero-3-phosphocholine, PAF) was investigated during acute lung injury induced by interleukin- $1{\alpha}$ (IL-1) in rats. An insufflation of IL-1 into the rat's trachea increased the acetyltransferase activity in the lung and the increase of PAF content was followed. As evidences of acute lung injury by neutrophilic respiratory burst, lung leak index, myeloperoxidase activity, numbers of neutrophils in the bronchoalveolar lavage fluid, neutrophilic adhesions to endothelial cells and NBT positive neutrophils were increased after IL-1 treatment. In addition, a direct instillation of PAF into the trachea caused acute lung leak and the experimental results showed a similar pattern in comparison with IL-1 induced acute lung injury. For the confirmation of oxidative stress during acute lung leak by IL-1 and PAF, a histochemical electron microscopy was performed. In IL-1 and PAF treated lungs of rats, the deposits of cerrous perhydroxide were found. To elucidate the role of PAF, an intravenous injection of PAF receptor antagonist, WEB 2086 was given immediately after IL-1 or PAF treatment. WEB 2086 decreased the production of hydrogen peroxide and the acute lung leak. In ultrastructural study, WEB 2086 mitigated the pathological changes induced by IL-1 or PAF. The nuclear factor kappa B (NFkB) was activated by PAF and this activation was inhibited by WEB 2086 almost completely. Based on these experimental results, it is suggested that the PAF produced in response to IL-1 through the remodeling pathway has the major role for acute lung injury by neutrophilic respiratory burst. In an additional experiment, we can also come to conclude that the activation of the NFkB by PAF is thought to be the fundamental mechanism to initiate the oxidative stress by neutrophils causing release of proinflammatory cytokines and activation of phospholipase $A_2$ .


  • 주제어

    Acute lung leak .   Interleukin-1 .   PAF .   NFkB .   Oxidative stress.  

 저자의 다른 논문

  • Park, Yoon-Yub (8)

    1. 1998 "Nitric Oxide Impairs the Recovery from Hemorrhagic Hypotension in Conscious Rats" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 2 (3): 345~351    
    2. 1998 "Effect of the Inhibition of PLA2 on Oxidative Lung Injury Induced by $Interleukin-1{\alpha}$" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 2 (5): 617~628    
    3. 1999 "Effect of the Inhibition of Phospholipase $A_2$ in Generation of Free Radicals in Intestinal Ischemia/Reperfusion Induced Acute Lung Injury" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 3 (3): 263~273    
    4. 1999 "PAF Contributes to Intestinal Ischemia/Reperfusion-Induced Acute Lung Injury through Neutrophilic Oxidative Stress" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 3 (4): 405~414    
    5. 2000 "호중구의 Respiratory Burst에 미치는 PLA2 및 PAF와 영향 : In vitro에서의 호중구의 산소기 생성 및 Apoptosis에 관한 연구" 결핵 및 호흡기 질환 = Tuberculosis and respiratory diseases 48 (6): 887~897    
    6. 2009 "Ischemia/reperfusion Lung Injury Increases Serum Ferritin and Heme Oxygenase-1 in Rats" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 13 (3): 181~187    
    7. 2010 "Role of the PLA2-Activated Neutrophilic Oxidative Stress in Oleic Acid-Induced Acute Lung Injury" Tuberculosis and respiratory diseases : TRD = 결핵 및 호흡기 질환 68 (2): 55~61    
    8. 2010 "The Intracisternal Administration of MEK Inhibitor Attenuates Mechanical and Cold Allodynia in a Rat Model of Compression of the Trigeminal Ganglion" International journal of oral biology : official journal of the Korean Academy of Oral Biology and the UCLA Dental Research Institute 35 (3): 75~81    

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