Ascorbate-mediated enhancement of reactive oxygen species generation from polymorphonuclear leukocytes: modulatory effect of nitric oxide
- 23 March 2004
- journal article
- Published by Oxford University Press (OUP) in Journal of Leukocyte Biology
- Vol. 75 (6), 1070-1078
- https://doi.org/10.1189/jlb.0903415
Abstract
Recent studies from our laboratory have demonstrated that ascorbate potentiated enzymatic synthesis of nitric oxide (NO) from polymorphonuclear leukocytes (PMNs). NO is known to modulate various function of PMNs such as chemotaxis, adherence, aggregation, and generation of reactive oxygen species (ROS). The role of ascorbate in the PMN phagocytosis, ROS generation, and apoptosis was thus evaluated in the present study. Ascorbate and its oxidized and cell-permeable analog, dehydroascorbate (DHA), did not affect the phagocytosis but enhanced ROS generation and apoptosis following treatment with Escherichia coli or arachidonic acid. A detailed investigation on the DHA-mediated response indicated that inhibitors of DHA uptake, reduced nicotinamide adenine dinucleotide phosphate oxidase, NO synthase, or ROS scavengers attenuated ROS generation. In DHA-treated cells, enhanced generation of peroxynitrite was also observed; thus, ascorbate-mediated ROS and reactive nitrogen species generation might mediate cytotoxicity toward the ingested microbes and subsequently, augmented PMN apoptosis. Results of the present study have helped in delineating the role of ascorbate in the modulation of NO-mediated ROS generation from PMNs.Keywords
Funding Information
- Department of Biotechnology
- Council of Scientific and Industrial Research
- Council of Scientific and Industrial Research
This publication has 54 references indexed in Scilit:
- Involvement of Oxidative Stress in Ascorbate-Induced Proapoptotic Death of PC12 CellsExperimental Neurology, 2001
- l-Ascorbic Acid Potentiates Endothelial Nitric Oxide Synthesis via a Chemical Stabilization of TetrahydrobiopterinJournal of Biological Chemistry, 2001
- Molecular Role of Ascorbate in Enhancement of NO Production in Activated Macrophage-Like Cell Line, J774.1.Journal of Nutritional Science and Vitaminology, 1999
- The requirement for and mobilization of calcium during induction by sodium ascorbate and by hydrogen peroxide of cell deathLife Sciences, 1996
- Cell death by oxidative stress and ascorbic acid regeneration in human neuroectodermal cell linesEuropean Journal Of Cancer, 1995
- Ascorbyl radical as natural indicator of oxidative stress: quantitative regularitiesFree Radical Biology & Medicine, 1994
- Enzymatic Basis for Altered Ascorbic Acid and Dehydroascorbic Acid Levels in DiabetesBiochemical and Biophysical Research Communications, 1993
- Nitric oxide, an endothelial cell relaxation factor, inhibits neutrophil superoxide anion production via a direct action on the NADPH oxidase.JCI Insight, 1992
- Ascorbic acid accumulation in plated human neutrophilsFEBS Letters, 1990
- The distribution of ascorbic acid between various cellular components of blood, in normal individuals, and its relation to the plasma concentrationBritish Journal of Nutrition, 1982