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pubmed:abstractText |
Quinone and hydroquinone forms of rifampin accumulated in normal polymorphonuclear leukocytes (PMN) (maximal cellular to extracellular concentration ratio [C/Emax] +/- standard error of the mean, 9.36 +/- 0.54 and 8.82 +/- 0.65, respectively, after 5 to 10 min) and chronic granulomatous disease PMN (C/Emax, 13.76 +/- 0.77 and 14.29, respectively). Uptake of rifampin was influenced by incubation temperature and extracellular pH but not by phorbol myristate acetate stimulation or metabolic inhibitors. At extracellular concentrations between 0.06 and 5.0 mg/liter, rifampin significantly reduced the number of staphylococci surviving inside chronic granulomatous disease PMN, thus compensating for the bactericidal defect inherent with this disease. Spontaneous migration and chemotaxis of normal PMN were unaffected by rifampin. However, phagocytosis of yeast particles and oxygen consumption of stimulated PMN were moderately depressed, and O2- production and chemiluminescence were significantly depressed in a dose-dependent manner. The bactericidal activity of normal PMN was not impaired. Inhibition of chemiluminescence and O2- release were also observed in a cell-free system. We conclude that rifampin possesses favorable characteristics for the effective elimination of intracellular microorganisms. Further studies are needed to evaluate the in vivo significance of ion scavenging by rifampin, which could be hazardous to immunocompromised patients.
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