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

J. Wang, R. Charboneau, S. Balasubramanian, R. A. Barke, H. H. Loh, S. Roy

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

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-γ 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.

Original languageEnglish (US)
Pages (from-to)527-536
Number of pages10
JournalJournal of Leukocyte Biology
Volume70
Issue number4
StatePublished - Oct 22 2001
Externally publishedYes

Keywords

  • Apoptosis
  • Induced nitric oxide synthase
  • Wild type
  • μ-opioid receptor knock-out

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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    Wang, J., Charboneau, R., Balasubramanian, S., Barke, R. A., Loh, H. H., & Roy, S. (2001). Morphine modulates lymph node-derived T lymphocyte function: Role of caspase-3, -8, and nitric oxide. Journal of Leukocyte Biology, 70(4), 527-536.