Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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Originally published online as doi:10.1189/jlb.0903415 on March 23, 2004

Published online before print March 23, 2004
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(Journal of Leukocyte Biology. 2004;75:1070-1078.)
© 2004 by Society for Leukocyte Biology

Ascorbate-mediated enhancement of reactive oxygen species generation from polymorphonuclear leukocytes: modulatory effect of nitric oxide

Prashant Sharma, Santhanam A.V. Raghavan, Rashmi Saini and Madhu Dikshit1

Division of Pharmacology, Central Drug Research Institute, Uttar Pradesh, India

1 Correspondence: Pharmacology Division, Central Drug Research Institute, Lucknow–26001, Uttar Pradesh, India. E-mail: madhudikshit{at}yahoo.com

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.

Key Words: ascorbic acid • peroxynitrite • apoptosis • phagocytosis




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