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Ascorbate and cysteine-mediated selective neutralisation of extracellular oxidants during N-formyl peptide activation of human phagocytes

  • Immunosuppression and Inflammation
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Abstract

The effects of sodium ascorbate and cysteine (2.5×10−5M–2.5×10−4 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 FMLPin vitro. Chemiluminescence studies were also performed using a whole-blood method. Cysteine (10−4 M–2.5×10−4M) and ascorbate (2.5×10−5M–2.5×10−4M) 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 luminolenhanced 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.

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Authors and Affiliations

  1. Division of Immunology, Department of Medical Microbiology, Institute of Pathology, University of Pretoria, P.O. Box 2034, 0001, Pretoria, Republic of South Africa

    Ronald Anderson, Pauline T. Lukey, Annette J. Theron & Ursula Dippenaar

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  1. Ronald Anderson
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  2. Pauline T. Lukey
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  3. Annette J. Theron
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  4. Ursula Dippenaar
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Anderson, R., Lukey, P.T., Theron, A.J. et al. Ascorbate and cysteine-mediated selective neutralisation of extracellular oxidants during N-formyl peptide activation of human phagocytes. Agents and Actions 20, 77–86 (1987). https://doi.org/10.1007/BF01965628

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  • DOI: https://doi.org/10.1007/BF01965628

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