| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1990: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
The effects of anti-inflammatory drugs (acetylsalicylic acid, ASA ; salicylic acid, SA ; indomethacin IM ; hydrocortisone, HC) on the respiratory burst oxidase (NADPH oxidase) from human neutrophils in both whole cell and fully soluble (cell-free) systems were investigated. These drugs were found to inhibit the superoxide generation by human neutrophils exposed to phorbol myristate acetate in a whole cell system and the activation of superoxide-generating NADPH oxidase by sodium dodecyl sulfate in cell-free systems. Concentrations of these drugs required for 50% inhibition of the oxidase (ID_<50>) were ; ASA (more than 3.0mM in the whole cell system and 1.35mM in the cell-free system), SA (more than 3.0mM in the whole cell system and 1.30mM in the cell-free system), IM (180muM in both systems) and HC (50muM in the whole cell system and 40, muM in the cell-free system). In addition, these drugs time-dependently inhibited the activation of NADPH oxidase in cell-free systems. In the cell-
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free system, all of the drugs did not change the Km values for NADPH of the oxidase. These results suggest that these anti-inflammatory drugs, especially HC and IM, inhibit the reconstitution (activation) of neutrophil NADPH oxidase enzyme in the cell-free (whole cell) system.
The superoxide generation of neutrophil NADPH oxidase from healthy subjects, patients with respiratory infections, and patients receiving effective antibiotics or steroids was investigated. In young healthy non-smokers, the mean oxidase activity of neutrophils in females was significantly lower than that in males. In healthy women, the mean oxidase activity was significantly lower in young non-smokers than in young smokers or the elderly. In young non-smokers, oxidase activity significantly increased during respiratory infections. In elderly non-smokers, however, no significant increase in oxidase activity was observed during respiratory infections. The mean oxidase activity in patients receiving steroids was very low. In experiments using cell-free activation system of NADPH oxidase, steroids were found to injure the membrane-bound components of the oxidase enzyme. These results suggest that decreased superoxide generation in patients receiving steroids may result from steroid-induced damage in the membrane-bound components of the NADPH oxidase system. The inhibitory effect of steroids on superoxide production may reduce bactericidal action of neutrophils, i. e., one defense mechanism of the body against many kinds of pathogens. Therefore, long-term therapy with steroids in the elderly should be avoided at all costs. Less
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