N-acetylcysteine improves in vitro the function of macrophages from mice with endotoxin-induced oxidative stress.
Reactive oxygen species (ROS) and proinflammatory cytokines produced by immune cells cause the oxidative stress involved in septic shock induced by endotoxin. This oxidative stress can be controlled to a certain degree by antioxidants, which is specially important for a type of immune cell, i.e. the phagocyte, that uses ROS to kill microorganisms and needs antioxidants in order to support its functions. In a previous study we have observed changes in several functions of peritoneal macrophages from BALB/c mice with lethal endotoxic shock caused by intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS) (100 mg/kg), which were associated with a high production of superoxide anion. N-acetylcysteine (NAC) is a thiolic antioxidant that improves the immune response, and we have observed that when administered intraperitoneally (150 mg/kg) at 30 min after LPS injection it counteracts the effects of LPS on macrophages and lymphocytes. In the present work, we have studied the in vitro effect of several concentrations of NAC (0.001, 0.01, 0.1, 1 and 2.5 mM) on the following functions: adherence to substrate, chemotaxis, ingestion of particles, ROS production and the release of tumor necrosis factor (TNFalpha) of peritoneal macrophages from BALB/c mice at 2, 4,12 and 24 h after LPS injection. The results show that the administration of NAC (especially at 0.1 mM) decreases raised adherence, ingestion, ROS production and TNFalpha levels in macrophages from animals injected with LPS, bringing these functions to values near those of control animals. These effects which seem to be linked to a modulation of NF-kappaB, suggest that the improvement of immune functions observed in previous work after injection of NAC to animals with endotoxic shock could be due to a direct action of this thiol antioxidant on immune cells.
Victor
Victor M
VM
Department of Animal Physiology, Faculty of Biology, Complutense University, Madrid, Spain.
De la Fuente
Monica
M
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000838:Anions; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D002448:Cell Adhesion; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress; D010587:Phagocytosis; D017382:Reactive Oxygen Species; D013481:Superoxides; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000838:Anions; D000975:Antioxidants; D004731:Endotoxins; D016166:Free Radical Scavengers; D005609:Free Radicals; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D000111:Acetylcysteine