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Morphine modulates lymph node‐derived T lymphocyte function: role of caspase‐3, ‐8, and nitric oxide
Author(s) -
Wang Jinghua,
Charboneau Richard,
Balasubramanian Sudha,
Barke Roderick A.,
Loh Horace H.,
Roy Sabita
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.70.4.527
Subject(s) - morphine , apoptosis , opioid , receptor , nitric oxide , lymph , opioid receptor , lymph node , nitric oxide synthase , pharmacology , lymphocyte , biology , caspase , immunology , endocrinology , medicine , programmed cell death , biochemistry , pathology
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. N G ‐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.