Ascorbate and cysteine-mediated selective neutralisation of extracellular oxidants during N-formyl peptide activation of human phagocytes.
The effects of sodium ascorbate and cysteine (2.5 X 10(-5) M-2.5 X 10(-4) M) on the intensity and profile of luminol-enhanced chemiluminescence, superoxide generation, extracellular myeloperoxidase (MPO) activity and auto-iodination were measured in purified human polymorphonuclear leukocytes activated by the leukoattractant FMLP in vitro. Chemiluminescence studies were also performed using a whole-blood method. Cysteine (10(-4) M-2.5 X 10(-4) M) and ascorbate (2.5 X 10(-5) M-2.5 X 10(-4) M) caused significant inhibition of the early extracellular peak of FMLP-activated chemiluminescence and increased the intensity of the later occurring intracellular peak in both PMNL and blood. At the same concentrations both agents scavenged superoxide released by FMLP-activated PMNL, inhibited oxidant generation by extracellular MPO and decreased FMLP-induced auto-oxidation of PMNL. Administration of a single 1 gram oral dose of ascorbate to adult human volunteers was associated with significant reduction and enhancement respectively of the extracellular and intracellular luminol-enhanced chemiluminescence responses of FMLP-activated blood. These results show that the water soluble anti-oxidants cysteine and especially ascorbate selectively neutralise the reactivity of harmful reactive oxidants released by phagocytes, whilst the intracellular generation of antimicrobial oxidants remains intact.
D000328:Adult; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D003545:Cysteine / Q000494:pharmacology*; D006801:Humans; D007958:Leukocyte Count; D008163:Luminescent Measurements; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism
D000975:Antioxidants; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009195:Peroxidase; D003545:Cysteine; D001205:Ascorbic Acid