TREM-1 multimerization is essential for its activation on monocytes and neutrophils
| العنوان: | TREM-1 multimerization is essential for its activation on monocytes and neutrophils |
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| المؤلفون: | Carrasco, Kevin, Boufenzer, Amir, Jolly, Lucie, Le Cordier, Helene, Wang, Guanbo, Heck, Albert Jr, Cerwenka, Adelheid, Vinolo, Emilie, Nazabal, Alexis, Kriznik, Alexandre, Launay, Pierre, Gibot, Sebastien, Derive, Marc, Afd Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Biomolecular Mass Spectrometry and Proteomics |
| المساهمون: | Afd Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Biomolecular Mass Spectrometry and Proteomics, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), INOTREM SA, Faculté de Médecine [Nancy], Université de Lorraine (UL)-Université de Lorraine (UL), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Utrecht University [Utrecht], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), CovalX, Ingénierie, Biologie et Santé en Lorraine (IBSLor), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Inatherys |
| المصدر: | Cellular Immunology, 16, 460. Academic Press Inc. Cellular and molecular immunology Cellular and molecular immunology, Nature Publishing Group/Chinese Society of Immunology, 2018, 16 (5), pp.460-472. ⟨10.1038/s41423-018-0003-5⟩ Cell Mol Immunol |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Lipopolysaccharides, TREM-1, Myeloid, medicine.medical_treatment, Immunology, Primary Cell Culture, Article, Cell membrane, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, neutrophils, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Immunology and Allergy, Humans, multimerization, Calcium Signaling, Receptor, Adaptor Proteins, Signal Transducing, Inflammation, Innate immune system, Chemistry, Cell Membrane, Receptor Aggregation, Membrane Proteins, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, U937 Cells, Immunity, Innate, Triggering Receptor Expressed on Myeloid Cells-1, Cell biology, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, Cytokine, Ectodomain, activation, Protein Multimerization, Reactive Oxygen Species, monocytes, Intracellular, 030215 immunology |
| الوصف: | International audience; The triggering receptor expressed on myeloid cells-1 (TREM-1) is a receptor expressed on innate immune cells. By promoting the amplification of inflammatory signals that are initially triggered by Toll-like receptors (TLRs), TREM-1 has been characterized as a major player in the pathophysiology of acute and chronic inflammatory diseases, such as septic shock, myocardial infarction, atherosclerosis, and inflammatory bowel diseases. However, the molecular events leading to the activation of TREM-1 in innate immune cells remain unknown. Here, we show that TREM-1 is activated by multimerization and that the levels of intracellular Ca2+ release, reactive oxygen species, and cytokine production correlate with the degree of TREM-1 aggregation. TREM-1 activation on primary human monocytes by LPS required a two-step process consisting of upregulation followed by clustering of TREM-1 at the cell surface, in contrast to primary human neutrophils, where LPS induced a rapid cell membrane reorganization of TREM-1, which confirmed that TREM-1 is regulated differently in primary human neutrophils and monocytes. In addition, we show that the ectodomain of TREM-1 is able to homooligomerize in a concentration-dependent manner, which suggests that the clustering of TREM-1 on the membrane promotes its oligomerization. We further show that the adapter protein DAP12 stabilizes TREM-1 surface expression and multimerization. TREM-1 multimerization at the cell surface is also mediated by its endogenous ligand, a conclusion supported by the ability of the TREM-1 inhibitor LR12 to limit TREM-1 multimerization. These results provide evidence for ligand-induced, receptor-mediated dimerization of TREM-1. Collectively, our findings uncover the mechanisms necessary for TREM-1 activation in monocytes and neutrophils. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0008-8749 1672-7681 2042-0226 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bb1dd2917f8ddf341b1378085345629bTest https://dspace.library.uu.nl/handle/1874/391029Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bb1dd2917f8ddf341b1378085345629b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00088749 16727681 20420226 |
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