science pharmaceutical expo biotech jobs
Originally published online as doi:10.1189/jlb.1203639 on March 23, 2004

Published online before print March 23, 2004
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jlb.1203639v1
75/6/1131    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bhat, R. S.
Right arrow Articles by Singhal, P. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bhat, R. S.
Right arrow Articles by Singhal, P. C.
(Journal of Leukocyte Biology. 2004;75:1131-1138.)
© 2004 by Society for Leukocyte Biology

Morphine-induced macrophage apoptosis: oxidative stress and strategies for modulation

Rajani S. Bhat, Madhu Bhaskaran, Anil Mongia, Naoko Hitosugi and Pravin C. Singhal1

Department of Medicine, Long Island Jewish Medical Center and North Shore University Hospital, New Hyde Park, New York

1 Correspondence: Division of Kidney Diseases and Hypertension, Long Island Jewish Medical Center, 410 Lakeville Road, Suite #207, New Hyde Park, NY 11040. E-mail: singhal{at}lij.edu

Occurrence of macrophage apoptosis has been implicated for the altered immune function found in an opiate milieu. In the present study, we evaluated the role of oxidative stress in morphine-induced macrophage apoptosis. Morphine promoted the apoptosis of macrophages. This effect of morphine was associated with the production of superoxide and nitric oxide (NO). Antioxidants provided protection against morphine-induced macrophage injury. In addition, diphenyleneiodonium chloride, an inhibitor of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, attenuated the proapoptotic effect of morphine. Antitransforming growth factor-ß (anti-TGF-ß) antibody and propranolol (an inhibitor of the phospholipase D pathway) inhibited morphine-induced superoxide generation as well as apoptosis. N'-Tetraacetic acid tetra (acetoxymethyl) ester, a calcium-chelating agent, inhibited morphine-induced apoptosis, whereas thapsigargin (a calcium agonist) stimulated macrophage apoptosis under basal as well as morphine-stimulated states. These studies suggest that morphine-induced macrophage apoptosis is mediated through downstream signaling involving TGF-ß and NO production. Moreover, there is NADPH oxidation activation involving phospholipase D and Ca2+, leading to the generation of superoxide. In in vivo studies, administration of N-acetyl cysteine and preinduction of heme oxygenase activity and epoetin {alpha} prevented morphine-induced peritoneal macrophage apoptosis, thus further confirming the role of oxidative stress in morphine-induced macrophage apoptosis.

Key Words: opiates • signal transduction • nitric oxide • reactive oxygen species




This article has been cited by other articles:


Home page
 Anesth. Analg.Home page
C.-F. Lam, P.-J. Chang, Y.-S. Huang, Y.-H. Sung, C.-C. Huang, M.-W. Lin, Y.-C. Liu, and Y.-C. Tsai
Prolonged Use of High-Dose Morphine Impairs Angiogenesis and Mobilization of Endothelial Progenitor Cells in Mice
Anesth. Analg., August 1, 2008; 107(2): 686 - 692.
[Abstract] [Full Text] [PDF]