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Abstract
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.
Abbreviations:
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)To read this article in full you will need to make a payment
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Article info
Publication history
Accepted:
January 31,
1994
Received in revised form:
January 25,
1994
Received:
September 7,
1993
Footnotes
☆Supported by grant no. 91.14.01 C, Ricerca Corrente Gaslini and grant no. 91.14.01 F, Ricerca Finalizzata Gaslini “Farmacogenetica.”
Identification
Copyright
© 1994 Published by Elsevier Inc.