Opioids modulate constitutive B-lymphocyte secretion

Vassou, Despoina; Bakogeorgou, Efstathia; Kampa, Marilena; Dimitriou, Helen; Hatzoglou, Anastassia; Castanas, Elias

doi:10.1016/j.intimp.2008.01.002

Cited by 30 publications

(18 citation statements)

References 66 publications

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“…In this regard, morphine is known to dramatically affect innate and adaptive immune responses [72], [73], [74], [75]. For example, morphine affects lymphocyte proliferation [76], [77], natural killer T-cell activities [78], [79], antibody production [80], [81], and the number of circulating leukocytes [82]. Inhibition of phagocyte function, such as chemotaxis, phagocytosis, and surface receptor expression after morphine exposure in vitro is, in part, a consequence of NO synthesis [69] and involves the modulation of the transcription factors NF-κB and AP-1 [67], [68], [70], [83], [84].…”

Section: Discussionmentioning

confidence: 99%

Endogenous Morphine Levels Are Increased in Sepsis: A Partial Implication of Neutrophils

et al. 2010

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BackgroundMammalian cells synthesize morphine and the respective biosynthetic pathway has been elucidated. Human neutrophils release this alkaloid into the media after exposure to morphine precursors. However, the exact role of endogenous morphine in inflammatory processes remains unclear. We postulate that morphine is released during infection and can be determined in the serum of patients with severe infection such as sepsis.MethodologyThe presence and subcellular immunolocalization of endogenous morphine was investigated by ELISA, mass spectrometry analysis and laser confocal microscopy. Neutrophils were activated with Interleukin-8 (IL-8) or lipopolysaccharide (LPS). Morphine secretion was determined by a morphine-specific ELISA. μ opioid receptor expression was assessed with flow cytometry. Serum morphine concentrations of septic patients were determined with a morphine-specific ELISA and morphine identity was confirmed in human neutrophils and serum of septic patients by mass spectrometry analysis. The effects of the concentration of morphine found in serum of septic patients on LPS-induced release of IL-8 by human neutrophils were tested.Principal FindingsWe confirmed the presence of morphine in human neutrophil extracts and showed its colocalisation with lactoferrin within the secondary granules of neutrophils. Morphine secretion was quantified in the supernatant of activated human polymorphonuclear neutrophils in the presence and absence of Ca2+. LPS and IL-8 were able to induce a significant release of morphine only in presence of Ca2+. LPS treatment increased μ opioid receptor expression on neutrophils. Low concentration of morphine (8 nM) significantly inhibited the release of IL-8 from neutrophils when coincubated with LPS. This effect was reversed by naloxone. Patients with sepsis, severe sepsis and septic shock had significant higher circulating morphine levels compared to patients with systemic inflammatory response syndrome and healthy controls. Mass spectrometry analysis showed that endogenous morphine from serum of patient with sepsis was identical to poppy-derived morphine.ConclusionsOur results indicate that morphine concentrations are increased significantly in the serum of patients with systemic infection and that morphine is, at least in part, secreted from neutrophils during sepsis. Morphine concentrations equivalent to those found in the serum of septic patients significantly inhibited LPS-induced IL-8 secretion in neutrophils.

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Section: Discussionmentioning

confidence: 99%

Endogenous Morphine Levels Are Increased in Sepsis: A Partial Implication of Neutrophils

et al. 2010

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“…Both endogenous and exogenous μ-, κ- and δ-opioid compounds exert broad immunomodulatory activity, and this includes inhibition of antibody responses (Johnson et al 1982; Heijnen et al 1986; Taub et al 1991; Bussiere et al 1992; Bussiere et al 1993; Vassou et al 2008), phagocytic cell function (Rojavin et al 1993; Casellas et al 1991; Singh et al 2007; Wang et al 2008; Tomassini et al 2003), and natural killer cell activity (Weber and Pert 1989; Bayer et al 1990; Gaveriaux-Ruff et al 1998). Studies from a number of laboratories have established, using reverse transcriptasepolymerase chain reaction (RT-PCR)-based techniques, that leukocytes express the μ-, κ-, and δ-opioid receptors (Chuang et al 1994; Chuang et al 1995; Belkowski et al 1995b; Alicea et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Regulation of Mu Opioid Receptor Expression in Developing T Cells

Zhang

Belkowski

Briscoe

et al. 2012

J Neuroimmune Pharmacol

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We have previously reported that functionally active μ-opioid receptors (MOR) are constitutively expressed at relatively low levels by developing T cells in the thymus. However, very little is known about the regulation of MOR expression by immature T cells. In this report, we first attempted to determine the effect of T cell receptor-induced T cell activation on the expression of MOR. We activated T cells with either the combination of anti-CD3 and CD28, or with superantigen, and observed a substantial increase in MOR transcript expression. We also chose to examine the effect of cytokine-mediated T cell activation on the expression of this opioid receptor. We selected certain cytokines that play a role in T cell development and are known to be present at functional levels in the thymus gland. Our results show that interferon γ (IFNγ), IL-1β, and IL-2, and in particular transforming growth factor-β (TGFβ), all induced significant increases in MOR transcript expression. On the other hand, both TNFα and IL-7 exhibited much weaker effects on MOR expression. These results show that MOR expression by developing T cells is strongly regulated by several cytokines involved in T cell development in the thymus gland.

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“…Predominant channels found in lymphocytes are voltage-gated K+ channels and several lines of evidence suggest that these channels are involved in lymphocyte function/s. Vassou et al (2008) have suggested that the effects of opioids on B-lymphocytes may be attributed to interplay between distinct cell populations. Findings from our lab show that the presence 118G allele not only impacts the amount of drug consumed, but also influences the immunomodulation caused by exogenous opiates.…”

Section: Resultsmentioning

confidence: 99%

“…The individuals homozygous for AA genotype seem to be more vulnerable to suppression of humoral immunity (antibody production by B cells) while those with GG genotype could be protected against such depression of B-cell function. Indeed, Vassou et al (2008) have shown that opiates like morphine, alpha S1 -casomorphin and ethylketocyclazocine modulate antibody and cytokine secretion by multiple myeloma cells in a cell line-dependent manner and decrease antibody secretion by normal B-lymphocytes. Data from both transfected cells and human autopsy brain tissue from carriers of 118G allele indicate that this allele may produce deleterious effect on mRNA and corresponding MOR protein yield (Janicki et al, 2006).…”

Section: Resultsmentioning

confidence: 99%