Endogenous Morphine Levels Are Increased in Sepsis: A Partial Implication of Neutrophils
| العنوان: | Endogenous Morphine Levels Are Increased in Sepsis: A Partial Implication of Neutrophils |
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| المؤلفون: | Benoît-Joseph Laventie, Marie-Hélène Metz-Boutigue, Thomas Lavaux, Yannick Goumon, Elise Glattard, Alain Van Dorsselaer, Didier A. Colin, Ingeborg Welters, Alexis Laux, Sylvie Dirrig-Grosch, Arnaud Muller, Alexander R. Schmidt, Francis Schneider, Dan-Dan Zhang, François Delalande, Dominique Aunis |
| المساهمون: | Physiopathologie du système nerveux., Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), University of Liverpool, Universitatsklinikum Giessen und Marburg [Marburg,Germany], Service de Réanimation Médicale [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Physiopathologie des arthrites, Université Louis Pasteur - Strasbourg I, Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Goumon, Yannick |
| المصدر: | PLoS ONE PLoS ONE, 2010, 5 (1), pp.e8791. ⟨10.1371/journal.pone.0008791⟩ PLoS ONE, Vol 5, Iss 1, p e8791 (2010) |
| بيانات النشر: | Public Library of Science, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Lipopolysaccharides, Neutrophils, Receptors, Opioid, mu, lcsh:Medicine, Endogeny, MESH: Flow Cytometry, Pharmacology, MESH: Neutrophils, Lymphocyte Activation, Biochemistry, [SCCO]Cognitive science, Critical Care and Emergency Medicine/Sepsis and Multiple Organ Failure, Tandem Mass Spectrometry, MESH: Microscopy, Confocal, lcsh:Science, MESH: Sepsis, Multidisciplinary, Microscopy, Confocal, medicine.diagnostic_test, Morphine, Chemistry, Alkaloid, MESH: Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Immunohistochemistry, Electrophoresis, Polyacrylamide Gel, medicine.drug, Research Article, Blotting, Western, MESH: Receptors, Opioid, mu, Enzyme-Linked Immunosorbent Assay, Flow cytometry, Sepsis, Immune system, medicine, MESH: Blotting, Western, Humans, Secretion, Interleukin 8, MESH: Lymphocyte Activation, MESH: Humans, lcsh:R, Interleukin-8, MESH: Tandem Mass Spectrometry, MESH: Immunohistochemistry, [SCCO] Cognitive science, Cell Biology, medicine.disease, MESH: Interleukin-8, MESH: Morphine, Immunology, lcsh:Q, MESH: Lipopolysaccharides, MESH: Electrophoresis, Polyacrylamide Gel |
| الوصف: | International audience; Background: Mammalian 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.Methodology: The 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. mu 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 findings: We 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 Ca(2+). LPS and IL-8 were able to induce a significant release of morphine only in presence of Ca(2+). LPS treatment increased mu 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.Conclusions: Our 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0008791⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c8f9eb2d29de44e40b7083df21807fbf http://europepmc.org/articles/PMC2808358 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c8f9eb2d29de44e40b7083df21807fbf |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0008791⟩ |