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| 1 | TREM-1 multimerization is essential for its activation on monocytes and neutrophils显示文摘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 Ca 2+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. | Kevin Carrasco Amir Boufenzer Lucie Jolly Helene Le Cordier Guanbo Wang Albert JR Heck Adelheid Cerwenka Emilie Vinolo Alexis Nazabal Alexandre Kriznik Pierre Launay Sebastien Gibot Marc Derive | 2019 | Cellular & Molecular Immunology2019，16，5： | 13 |
| 2 | Potentiation of NETs release is novel characteristic of TREM-1 activation and the pharmacological inhibition of TREM-1 could prevent from the deleterious consequences of NETs release in sepsis显示文摘During sepsis,neutrophil activation induces endothelial cell(EC)dysfunction partly through neutrophil extracellular trap(NET)release.The triggering receptor expressed on myeloid cell-1(TREM-1)is an orphan immune receptor that amplifies the inflammatory response mediated by Toll-like receptor-4(TLR4)engagement.Although the key role of TLR4 signaling in NETosis is known,the role of TREM-1 in this process has not yet been investigated.Here,we report that TREM-1 potentiates NET release by human and murine neutrophils and is a component of the NET structure.In contrast,pharmacologic inhibition or genetic ablation of TREM-1 decreased NETosis in vitro and during experimental septic shock in vivo.Moreover,isolated NETs were able to activate ECs and impair vascular reactivity,and these deleterious effects were dampened by TREM-1 inhibition.TREM-1 may,therefore,constitute a new therapeutic target to prevent NETosis and associated endothelial dysfunction. | Amir Boufenzer Kevin Carrasco Lucie Jolly Benjamin Brustolin Elisa Di-Pillo Marc Derive Sébastien Gibot | 2021 | Cellular & Molecular Immunology2021，18，2： | 9 |
| 3 | sTREM-1 is a specific biomarker of TREM-1 pathway activation显示文摘TREM-1(triggering receptor expressed on myeloid cells-1)is a transmembrane receptor expressed by innate immune cells,including endothelial cells and platelets.TREM-1 is a crucial mediator of septic shock that acts by synergizing with Toll-like receptors(TLRs)to amplify the inflammatory responses to pathogens,thus promoting sepsis-induced immune dysregulation and organ dysfunction[1,2,3]. | Lucie Jolly Kévin Carrasco Margarita Salcedo-Magguilli Jean-Jacques Garaud Simon Lambden Tom van der Poll Alexandre Mebazaa Pierre-François Laterre Sebastien Gibot Amir Boufenzer Marc Derive | 2021 | Cellular & Molecular Immunology2021，18，8： | 8 |
| 4 | Somatostatin-Probably the most widely effective gastrointestinal hormone in human body显示文摘Somatostatin-ProbablythemostwidelyefectivegastrointestinalhormoneinhumanbodyHUANGXiangQianSubjectHeadingssomatostatin/physio... | HUANG Xiang Qian Keywords somatostatin/physiology somatostatin/analogs and derivatives receptors, somatostatin octreotide/diagnostic use octreotide/therapeutic use | 1997 | World Journal of Gastroenterology1997，3，4： | 4 |
| 5 | Part 2: structure/property relationships-foaming, disper- sion, and wetting显示文摘 | Piispanen P S Persson M Claesson P Surface properties of surfaetants derived from natural products | 2004 | Journal of Surfaetants and Deter- gents2004，7，2： | 1 |
| 6 | Urine sTREM-1 assessment in diagnosing sepsis and sepsis-related acute kidney injury显示文摘 | Derive M Gibot S | 2011 | Crit Care2011，15，6： | 1 |
| 7 | Platelet aggregates- genitor cell proliferation and and foam cells is mediated by in vitro 显示文摘 | Stellos K Seizer P Bigalke induced human CD34 + pro different stromal Hemost iation to macrophages cell derived factor 1 B | 2010 | Semin Thromb2010，36，2： | 1 |
| 8 | CHEMICAL STUDIES ON QINGHAOSU (ARTEMISININE)显示文摘 | China Cooperative Research Group on Qinghaosu and Its Derivatives as Antimalarials | 1982 | Journal of Traditional Chinese Medicine1982，，01： | 1 |
| 9 | Clinical studies on the treatment of malaria with qinghaosu and its derivatives显示文摘 | China Coorperative Research Group on Qinghosu and Its Derivatives as Antimalarials | 1982 | J Tradit Chin Med1982，2，1： | 1 |
| 10 | 显示文摘 | EFSA Guidance document of the Scientific Panel on Generically Modified Organisms for the risk assessment of genetically modified plants and derived food and feed | 2006 | EFSA J2006，，9： | 1 |
| 11 | Triggering receptor expressed on myeloid ceils - 1 as a new therapeutic target during inflammatory diseases 显示文摘 | Derive M Massin F Gibot S | 2010 | Self Nonself2010，1，3： | 1 |
| 12 | 7 ceils via down regulation of MAPK/NF-B signaling 显示文摘 | Cheng Y W Chang C Y Lin K L Shikonin derivatives inhibited Lt-induced NOS in RAW264 | 2008 | J Ethnopharmacol2008，120，2： | 1 |
| 13 | THE CHEMISTRY AND SYNTHESIS OF QINGHAOSU DERIVATIVES显示文摘 | China Cooperative Research Group on Qinghaosu and Its Derivatives as Antimalarials | 1982 | Journal of Traditional Chinese Medicine1982，，01： | 1 |
| 14 | Triggering receptor expressed on myeloid cells-1 as a new therapeutic target during inflammatory diseases显示文摘 | Derive M Massin F Gibot S | 2010 | Self Nonself2010，1，3： | 1 |
| 15 | Myeloid-derived suppressor cells control microbial sepsis 显示文摘 | Derive M Bouazza Y Alauzet C | 2012 | Intensive Care Med2012，38，6： | 1 |
| 16 | Novel Biodegradable from Cotton Cellulose and Suecinic Anhydride Synthesis and Characterization显示文摘 | Yoshimura T Matsuo K Superabsorbent Hydrogels Derived Fujioka R | 2006 | Journal of Applied Polymer Science2006，99，： | 1 |
| 17 | Studies on the Pharmacokinetics of Qinghaosu and Its Derivatives显示文摘 | China Cooperatives Research Group on Qinghaosu and Its Derivatives as Antimalarials | 1982 | Trad Chin Med1982，2，1： | 1 |
| 18 | rithm显示文摘 | Matthews R On the derivation of a chaotic encryptionalg | 1989 | Cryptologia1989，，1： | 1 |
| 19 | from the on humanmalignant brain tumor cells 显示文摘 | Scheck A C Perry K Hank N Anticancer activity of extracts derived mature roots of Scutellaria baiccdensis C | 2006 | BMC Comple- ment Altern-Med2006，16，6： | 1 |
| 20 | Urine sTREM-1 assessment in diagnosing sepsis and sepsis-related acute kidney injury 显示文摘 | Derive M Gibot S | 2011 | Crit Care2011，15，6： | 1 |
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