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(Journal of Leukocyte Biology. 2001;70:527-536.)
© 2001 by Society for Leukocyte Biology

Morphine modulates lymph node-derived T lymphocyte function: role of caspase-3, -8, and nitric oxide

Jinghua Wang*, Richard Charboneau{dagger}, Sudha Balasubramanian*, Roderick A. Barke{dagger}, Horace H. Loh* and Sabita Roy*

* Department of Pharmacology, University of Minnesota, Minneapolis; and
{dagger} Department of Surgery, Veterans Affairs Medical Center, Minneapolis, Minnesota, and North Memorial Medical Center, Robbinsdale, Minnesota

Correspondence: Dr. Sabita Roy, Veterans Affairs Medical Center, Research RT 151, Room 3N 107, One Veterans Drive, Minneapolis, MN 55417. E-mail: royxx002{at}tc.umn.edu.

The major objective of this paper is to characterize the mechanism by which morphine modulates lymphocyte function and if these effects are mediated through the µ-opioid receptor. We evaluated the in vitro effects of morphine on lymphocytes that were freshly isolated from lymph nodes from wild type (WT) and µ-opioid receptor knock-out (MORKO) mice. Results show that morphine inhibits Con A-induced lymph node T-cell proliferation and IL-2 and IFN-{gamma} synthesis in a dose-dependent manner. This effect was abolished in lymph node cells isolated from MORKO mice. The inhibition of T-cell function with low-dose morphine was associated with an increase in caspase-3- and caspase-8-mediated apoptosis. The inhibition of T-cell function with high-dose morphine was associated with an increase in the inducible NO synthase mRNA expression. NG-nitro-L-arginine methyl ester (L-NAME) antagonized the apoptosis induced by high-dose morphine. Our results suggest that low-dose morphine, through the µ-opioid receptor, can induce lymph node lymphocyte apoptosis through the cleavage activity of caspase-3 and caspase-8. Morphine at high doses induces NO release. This effect of morphine is also mediated through the µ-opioid receptor present on the surface of macrophages.

Key Words: µ-opioid receptor knock-out • wild type • apoptosis • induced nitric oxide synthase




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