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KMID : 0383820070630060497
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Tuberculosis and Respiratory Diseases
2007 Volume.63 No. 6 p.497 ~ p.506
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Cytosolic Phospholipase A2 Activity in Neutrophilic Oxidative Stress of Platelet-activating Factor-induced Acute Lung Injury
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Kwon Young-Shik
Hyun Dae-Sung
Lee Young-Man
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Abstract
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Background: The present investigation was performed in rats and isolated human neutrophils in order to confirm the presumptive role of the positive feedback loop of cytosolic phospholipase A2 (cPLA2) activation by platelet- activating factor (PAF).
Methods: The possible formation of the positive feedback loop of the cPLA2 activation and neutrophilic respiratory burst was investigated in vivo and in vitro by measurement of the parameters denoting acute lung injury. In addition, morphological examinations and electron microscopic cytochemistry were performed for the detection of free radicals in the lung.
Results: Five hours after intratracheal instillation of PAF (5 microgram/rat), the lung leak index, lung myeloperoxidase (MPO) activity, the number of neutrophils and the concentration of cytokine-induced neutrophil chemoattractant (CINC) in bronchoalveolar lavage fluid were increased by PAF as compared with those of control rats. The NBT assay and cytochrome-c reduction assay revealed an increased neutrophilic respiratory burst in isolated human neutrophils following exposure to PAF. Lung and neutrophilic cPLA2 activity were increased following PAF exposure and exposure to hydrogen peroxide increased cPLA2 activity in the lung. Histologically, inflammatory findings of the lung were observed after PAF treatment. Remarkably, as determined by CeCl3 cytochemical electron microscopy, increased production of hydrogen peroxide was identified in the lung after PAF treatment.
Conclusion:PAF mediates acute oxidative lung injury by the activation of cPLA2, which may provoke the generation of free radicals in neutrophils.
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KEYWORD
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Acute Lung injury, PAF, cPLA2, Neutrophils
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