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

The processes of phagocytosis and intracellular killing of bacteria by alveolar macrophages (AMs) and polymorphonuclear leukocytes (PMNs) re sult in the production of reactive oxygen species that can induce self -damage to the phagocytic cells. N-Acetylcysteine (NAC), a mucolytic a gent used to treat chronic respiratory inflammatory disorders, possess es antioxidant properties and has therefore been used for the preventi on of damage induced by oxygen radicals. This study was designed to ev aluate whether NAC can interfere with the processes of phagocytosis an d intracellular killing of bacteria and protect the phagocytic cells f rom self-killing. Human AM, obtained by bronchoalveolar ravage, and pe ripheral blood PMNs were cultured with Staphylococcus aureus (American Type Culture Collection 25923 strain) in the presence of different co ncentrations 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 wer e equally effective as intracellular killers (p > 0.05), but were susc eptible 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 o f both AMs (p < 0.05) and PMNs (p < 0.05). This increased intracellula r killing was not associated with increased proportions of dead phagoc ytes either in AMs or PMNs cultures (p > 0.05, each comparison), sugge sting a protective effect of NAC on damage induced by toxic products g enerated during phagocytosis.