Pro-oxidative interactions of cobalt with human neutrophils.
The primary objectives of this study were to investigate the effects of cobalt(II) chloride (Co, 1.5-25 microM) on the reactivity of hydrogen peroxide (H2O2, 100 microM) or oxidants generated by activated human neutrophils. The prooxidative interactions of Co with H2O2 or cells were measured by luminol-enhanced chemiluminescence (LECL), and according to the extent of oxidative inactivation of added alpha-1-proteinase inhibitor (API). Cobalt dramatically potentiated the oxidation of luminol and API by both H2O2 and neutrophils activated with phorbol 12-myristate 13-acetate (5 ng/ml), without affecting the assembly of NADPH oxidase or the magnitude of oxygen consumption by the cells. Using 5,5-dimethyl-pyrolline 1-oxide-based electron spin resonance spectroscopy we were unable to detect hydroxyl radical formation by Co in the presence of either H2O2 or activated neutrophils, while the corresponding LECL responses were unaffected by the hydroxyl radical scavengers benzoate and mannitol (50 mM). These observations indicate that Co potentiates the reactivity of neutrophil-derived oxidants, primarily H2O2, which if operative in vivo during exposure to the heavy metal may pose the risk of oxidant- and protease-mediated tissue injury.
Ramafi
Grace J
GJ
National Centre for Occupational Health, Johannesburg, South Africa.
Theron
Annette J
AJ
Anderson
Ronald
R
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D003035:Cobalt / Q000633:toxicity*; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007202:Indicators and Reagents; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008163:Luminescent Measurements; D008165:Luminol; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects*; D016877:Oxidants / Q000633:toxicity; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D007202:Indicators and Reagents; D016877:Oxidants; D000515:alpha 1-Antitrypsin; D003035:Cobalt; D008165:Luminol; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases; D019272:Leukocyte Elastase