Impairment of raw 264.7 macrophage function by antiarrhythmic drugs.
The effect of the antiarrhythmic drugs lidocaine, quinidine and procainamide on macrophage function was investigated in RAW 264.7 mouse monocytic macrophage cell. Cells stimulated by either zymosan or phorbol ester were found to generate both superoxide (O2-) and H2O2. The production of O2 was detected as superoxide dismutase inhibitable ferricytochrome c reduction. H2O2 production was monitored in both chemical and flow cytometric fluorescent assays. Although all three drugs inhibited both O2 and H2O2 release in a dose-dependent manner, only quinidine was found to have significant inhibitory effects. The amounts of quinidine required to cause a 50% inhibition in O2 production in zymosan and phorbol ester stimulated cells were found to be 250 microM and 300 microM, respectively and the amounts required to cause one-half optimum levels of H2O2 production in these cells were found to be 50 microM and 100 microM, respectively. The effect of these drugs on O2 producing NADPH oxidase was investigated and only procainamide was found to have a significant effect (p < 0.001) in inhibiting the oxidase activity. Lidocaine and quinidine had no significant effect on the activation of the respiratory burst oxidase. A sensitive and convenient 'differential phagocytosis' assay was devised on the basis of number of particles engulfed by individual phagocytes using flow cytometric techniques. It appears to be remarkably free of interference and was applied to investigate the role of antiarrhythmic drugs on the phagocytosis of fluorescent latex beads. All three antiarrhythmic drugs inhibited phagocytosis of latex beads in a dose dependent manner irrespective of the number of particles phagocitized by the cells. The results of these studies do not conclusively establish a mechanism of action of these drugs on the generation of O2 and H2O2 by stimulated macrophages; nevertheless, it is interesting that all three drugs inhibited the phagocytic activity.
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Department of Biomedical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg 24061.
Misra
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D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002460:Cell Line; D006861:Hydrogen Peroxide / Q000097:blood; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects*; D013481:Superoxides / Q000097:blood
D000889:Anti-Arrhythmia Agents; D013481:Superoxides; D006861:Hydrogen Peroxide