Ascorbate and α-tocopherol differentially modulate reactive oxygen species generation by neutrophils in response to FcγR and TLR agonists.
Periodontitis, a ubiquitous chronic inflammatory disease, is associated with reduced antioxidant defences and neutrophil hyperactivity in terms of reactive oxygen species (ROS) generation. Its phenotype is thus characterized by oxidative stress. We have determined the effect of antioxidant micronutrients ascorbate and α-tocopherol on neutrophil ROS generation. Peripheral neutrophils from periodontally-healthy individuals (n = 20) were challenged with phorbol myristate acetate, IgG-opsonised Staphylococcus aureus, Fusobacterium nucleatum or PBS in the presence and absence of micronutrients (50 µM). Total and extracellular ROS were measured by luminol and isoluminol chemiluminescence respectively. Total and extracellular unstimulated, baseline ROS generation was unaffected by α-tocopherol, but inhibited by ascorbate and a combination of both micronutrients. Fcγ-receptor (Fcγ-R)-stimulated total or extracellular ROS generation was not affected by the presence of individual micronutrients. However, the combination significantly reduced extracellular FcγR-stimulated ROS release. Neither micronutrient inhibited TLR-stimulated total ROS, but the combination caused inhibition. Ascorbate and the micronutrient combination, but not α-tocopherol, inhibited extracellular ROS release by TLR-stimulated cells. Such micronutrient effects in vivo could be beneficial in reducing collateral tissue damage in chronic inflammatory diseases, such as periodontitis, while retaining immune-mediated neutrophil function.
School of Dentistry and MRC Centre for Immune Regulation, University of Birmingham, St Chads Queensway, Birmingham, UK.
Iain Lc
IL
Chapple
John B
JB
Matthews
Helen J
HJ
Wright
Ann E
AE
Scott
Helen R
HR
Griffiths
Melissa M
MM
Grant
D000328:Adult; D001205:Ascorbic Acid / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D016967:Fusobacterium nucleatum / Q000276:immunology*; D006801:Humans; D008297:Male; D018977:Micronutrients / Q000494:pharmacology*; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D010518:Periodontitis / Q000188:drug therapy / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017452:Receptors, IgG / Q000819:agonists; D013211:Staphylococcus aureus / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000276:immunology; D051193:Toll-Like Receptors / Q000819:agonists; D055815:Young Adult; D024502:alpha-Tocopherol / Q000494:pharmacology*
D018977:Micronutrients; D017382:Reactive Oxygen Species; D017452:Receptors, IgG; D051193:Toll-Like Receptors; D024502:alpha-Tocopherol; D013755:Tetradecanoylphorbol Acetate; D001205:Ascorbic Acid