Anti-μ-opioid-receptor IgG antibodies are commonly present in serum from healthy blood donors: evidence for a role in apoptotic immune cell death

Macé, G.; Jaume, Martial; Blanpied, Catherine; Stephan, Lionel; Coudert, Jérôme D.; Druet, Philippe; Dietrich, Gilles

doi:10.1182/blood-2002-01-0055

Cited by 13 publications

(12 citation statements)

References 54 publications

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“…Some of these immunomodulatory effects are dependent on stimulation of MOR in situ (Yin et al, 2000;Mace et al, 2002;Wang et al, 2002a, b). However, as exemplified in the T cell response to mitogens, the inhibitory effect of morphine is dependent on the tissue context.…”

Section: Discussionmentioning

confidence: 95%

“…The MOR mRNA undetectable in resting T lymphocytes and found in some activating conditions, is upregulated within an interleukin (IL)-4-or tumor necrosis factor-alpha-rich microenvironment (Gavériaux et al, 1995;Kraus et al, 2001Kraus et al, , 2003aMadden et al, 2001;Jaume et al, 2007;Borner et al, 2008). It is noteworthy that most of the immunosuppressive effects of morphine or stress-induced endogenous opioid release, such as apoptosis of spleen cells, reduction of both inflammation and natural killer cell activity, are mediated through MOR activation in mice (Shavit et al, 1984;Gavériaux-Ruff et al, 1998;Yin et al, 1999Yin et al, , 2000Mace et al, 2002;Wang et al, 2002a, b;Philippe et al, 2003). As a matter of fact, although DOR and enkephalins are together expressed in both CD4 þ T lymphocytes and antigen-presenting mature DCs, opioid receptor neutralization altered neither the antigen-induced proliferation of lymphocytes nor their sensitivity to apoptosis in vivo (Jaume et al, 2007).…”

Section: Introductionmentioning

confidence: 97%

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μ-Opioid Receptor Is Induced by IL-13 within Lymph Nodes from Patients with Sézary Syndrome

Bénard

Cavaillès

Boué

et al. 2010

Journal of Investigative Dermatology

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Endogenous opioid peptides mainly produced by neurons are also released by immune cells. They bind to mu- (mu-opioid receptor, MOR), delta-, and kappa-opioid receptors. On the basis of studies on mice showing that MOR is the main mediator of the deleterious effects of opioids on immunity, we wondered whether MOR, absent under normal conditions, is expressed in some pathological situations such as lymphomas. mRNA expression for all three opioid receptors was examined in lymph node biopsy samples from patients with non-Hodgkin's B-cell and T-cell lymphomas. We found that MOR and one of its ligands (enkephalin) are simultaneously expressed almost exclusively in lymph nodes from patients with Sézary cutaneous T cell lymphoma. As MOR was undetectable in circulating malignant T lymphocytes and in normal immune cells, we hypothesized that tumor-released cytokines might induce MOR expression in non-neoplastic lymph node cells. The correlation between mRNA levels of MOR and interleukin-13 (IL-13) within lymph nodes from Sézary patients led us to investigate the ability of IL-13 to upregulate MOR expression in normal immune cell subsets. We found that IL-13 upregulates MOR in activated Langerhans cells. Thus, our data suggest that, under pathological conditions, IL-13 overexpression might allow immune-derived endogenous opioids to down-modulate immune response.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 97%

μ-Opioid Receptor Is Induced by IL-13 within Lymph Nodes from Patients with Sézary Syndrome

Bénard

Cavaillès

Boué

et al. 2010

Journal of Investigative Dermatology

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“…Following reports of the presence of anti-MOR antibodies in the serum of healthy individuals (Mace et al, 1999b, Mace et al, 1999a, Mace et al, 2002), we focused upon autoantibody activity to DOR, a receptor shown to be expressed on peripheral blood cells, including T and B lymphocytes (Miller, 1996, Nguyen and Miller, 2002, Sharp, 2004, Sharp et al, 2001, Shen et al, 2005). Various groups have shown that the first and the third extracellular loops of the opioid receptors are critical for ligand binding specificity and functional activation of the receptor (Dietrich et al, 1998, Fadhil et al, 2004, Li et al, 1996, Mace et al., 1999b, Varga et al, 1996, Varga et al, 2004).…”

Section: Resultsmentioning

confidence: 99%

“…Apart from the expression of the opioid receptors on immune cells, another piece of evidence that supports the bidirectional network of communication between the opiate and immune system is the discovery that IgG autoantibodies directed against the human MOR are commonly present in the serum of healthy individuals (Mace et al, 1999a, Mace et al, 2002). These autoantibodies display an agonistic activity, demonstrated by the inhibition of forskolin stimulated cAMP accumulation.…”

Section: Introductionmentioning

confidence: 99%

“…These autoantibodies display an agonistic activity, demonstrated by the inhibition of forskolin stimulated cAMP accumulation. The autoantibodies bind to the first and third extracellular loops known to be involved in ligand binding and activation of the GPCR (Mace et al, 1999b, Mace et al, 2002, Dietrich et al, 1998, Mace et al., 2001). The earlier dogma of horror autotoxicus , according to which all autoantibodies were considered to contribute to autoimmune disease, has been replaced by the knowledge that the presence of a low level of circulating serum autoantibodies is, in fact, a hallmark of a healthy immune system (Quintana and Cohen, 2004, Shoenfeld and Toubi, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Autoantibodies to the δ-opioid receptor function as opioid agonists and display immunomodulatory activity

Ranganathan

Hao

Adelman

et al. 2009

Journal of Neuroimmunology

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In this report, we show that affinity purified human anti-Delta Opioid Receptor (DOR) autoantibodies from IVIG are specific to DOR and possess agonistic properties displayed by their ability to dramatically decrease forskolin stimulated cAMP accumulation. Anti-DOR autoantibody also caused phosphorylation of the opioid receptor. Anti-DOR autoantibody treatment showed a significant reduction in CXCR4 gene expression as well as surface protein expression. In contrast, anti-DOR autoantibody treatment significantly upregulated CCR5 gene and protein expression. The presence of anti-DOR autoantibodies in IVIG and their potent immunomodulatory activity is further evidence to support the crosstalk between the neuroendocrine and immune system.

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Morphine Induces Splenocyte Trafficking into the CNS

Olin

Roy

et al. 2011

J Neuroimmune Pharmacol

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Opioids significantly alter functional responses of lymphocytes following activation. Morphine, an opioid derivative, alters the Th1 to Th2 response and modulates functional responses such as cytolytic activity and proliferation. Although there has been extensive research involving morphine’s effects on lymphocytes, little is known about the effects morphine has on lymphocyte trafficking. The objective of the study was to use in vivo bioluminescent imaging to determine morphine’s effect on the trafficking pattern of splenocytes systemically and into the CNS following a neuroinflammatory stimulus. A neuroinflammatory response was induced by intracerebrally administering a DNA plasmid producing IFN-γ in morphine-dependent or placebo wildtype mice. Mice with or without a neurostimulus received adoptively transferred firefly luciferase transgenic splenocytes and were imaged using a charge-coupled device camera. Morphine dependence significantly altered the inherent ability of splenocytes to traffic into the spleen, and lead to non-directed chaotic trafficking throughout the animal, including the CNS. The morphine-mediated effects on trafficking were blocked by naltrexone. Morphine dependence intensified splenocyte infiltration into the CNS following neuroinflammation induced by IFN-γ gene transfer. The study determined that morphine severely altered the ability of non-activated splenocytes to home to the spleen, inducing chaotic extrasplenic trafficking thoughout the animals. Following a neuroinflammatory response, morphine exacerbated infiltration into the CNS.

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Anti-μ-opioid-receptor IgG antibodies are commonly present in serum from healthy blood donors: evidence for a role in apoptotic immune cell death

Cited by 13 publications

References 54 publications

μ-Opioid Receptor Is Induced by IL-13 within Lymph Nodes from Patients with Sézary Syndrome

μ-Opioid Receptor Is Induced by IL-13 within Lymph Nodes from Patients with Sézary Syndrome

Autoantibodies to the δ-opioid receptor function as opioid agonists and display immunomodulatory activity

Morphine Induces Splenocyte Trafficking into the CNS

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