Original article| Volume 124, ISSUE 2, P293-301, August 1994

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N-Acetylcysteine enhances in vitro the intracellular killing of Staphylococcus aureus by human alveolar macrophages and blood polymorphonuclear leukocytes and partially protects phagocytes from self-killing

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      The processes of phagocytosis and intracellular killing of bacteria by alveolar macrophages (AMs) and polymorphonuclear leukocytes (PMNs) result in the production of reactive oxygen species that can induce self-damage to the phagocytic cells. N-Acetylcysteine (NAC), a mucolytic agent used to treat chronic respiratory inflammatory disorders, possesses antioxidant properties and has therefore been used for the prevention of damage induced by oxygen radicals. This study was designed to evaluate whether NAC can interfere with the processes of phagocytosis and intracellular killing of bacteria and protect the phagocytic cells from self-killing. Human AM, obtained by bronchoalveolar lavage, and peripheral blood PMNs were cultured with Staphylococcus aureus (American Type Culture Collection 25923 strain) in the presence of different concentrations of NAC (1,10, and 100 mg/L) and two chromophores (4′, 6′-diamidino-2-phenylindole dihydrochloride and propidium iodide), which identify live or dead bacteria and dead phagocytes. As compared with PMNs, AMs were more effective in ingesting bacteria (p < 0.05) and were equally effective as intracellular killers (p>0.05), but were susceptible to a significantly higher rate of self-killing (p < 0.01). The presence of NAC in the cell cultures at the highest dose tested (100 mg/L) induced a significant enhancement of the bactericidal activity of both AMs (p < 0.05) and PMNs (p < 0.05). This increased intracellular killing was not associated with increased proportions of dead phagocytes either in AMs or PMNs cultures (p>0.05, each comparison), suggesting a protective effect of NAC on damage induced by toxic products generated during phagocytosis.


      AMs (alveolar macrophages), BAL (bronchoalveolar lavage), CFU (colony forming units), DAPI (4′, 6′-diamidino-2-phenylindole dihydrochloride), HEPES (N-(2-hydroxyethyl)piperazine-N′-(2-ethanesulfonic acid)), NAC (N-acetylcysteine), NADPH (reduced form of nicotinamide-adenine dinucleotide phosphate), PI (propidium iodide), PMNs (polymorphonuclear leukocytes), TPA (tetradecanoyl-phorbol-acetate)
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