Soluble Trem-like Transcript-1 Regulates Leukocyte Activation and Controls Microbial Sepsis

Derive, Marc; Bouazza, Youcef; Sennoun, N.; Marchionni, Sandra; Quigley, Laura; Washington, Valance; Massin, Frédéric; Max, Jean‐Pierre; Ford, Jill; Alauzet, Corentine; Lévy, Bruno; McVicar, Daniel W.; Gibot, Sébastien

doi:10.4049/jimmunol.1102674

Cited by 102 publications

(100 citation statements)

References 32 publications

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“…Considering that inhibition of Trem-1 only occurs during the first 5 days after MI (the LR12 half-life is short), 8 we thus speculate that the initial modulation of the inflammatory response must be responsible for this late-onset ventricular function improvement.…”

Section: Discussionmentioning

confidence: 99%

“…TREM-1 activation can be limited by the use of an inhibitory peptide (LR12) that we previously reported to have protective effects during septic shock. [8][9][10] On the opposite, TREM-1 can be engaged by an agonistic mAb (Trem-1 mAb). 6 Although mAb administration decreased survival, LR12 treatment was associated with a reduced death rate, not different to the one observed in Trem-1 Figure 1F).…”

Section: Trem-1 Genetic Invalidation Thus Improved Heart Function Andmentioning

confidence: 99%

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TREM-1 Mediates Inflammatory Injury and Cardiac Remodeling Following Myocardial Infarction

Boufenzer

Lemarié

Simon

et al. 2015

Circulation Research

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119

122

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A cute myocardial ischemia induces an intense activation of the immune system leading to cytokines and chemokines production 1,2 and to the recruitment of neutrophils and mononuclear cells in the infarcted area.3,4 Early proinflammatory signals are crucial in mediating the response to injury, regulating clearance of dead cardiac myocytes and initiating the cellular events necessary for wound healing. However, optimal healing requires activation of inhibitory mechanisms that suppress cytokine and chemokine synthesis and mediate resolution of the inflammatory infiltrate. Therefore, limiting the inflammatory response amplification seems to be important for containment of injury and optimal infarct healing. Triggering receptor expressed on myeloid cells-1 (TREM-1) is an immune-receptor expressed by neutrophils, macrophages, and mature monocytes that acts as an amplifier of the innate immune response.6 It has been shown that blockade of TREM-1 activation by short inhibitory peptides or fusion protein protected from hyper-responsiveness and death in various models of severe infections.

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Section: Discussionmentioning

confidence: 99%

Section: Trem-1 Genetic Invalidation Thus Improved Heart Function Andmentioning

confidence: 99%

TREM-1 Mediates Inflammatory Injury and Cardiac Remodeling Following Myocardial Infarction

Boufenzer

Lemarié

Simon

et al. 2015

Circulation Research

Self Cite

119

122

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“…A bolus of 5 mg/kg (in 60 mL) was intravenously delivered over 30 min, then a 1 mg/kg per hour (15 mL/h) infusion was started and lasted throughout the study period. This dosage was derived from previous experiments performed in rodents (22). Importantly, the intensivist in charge of the animal was blinded for the given treatment, which was prepared by an independent investigator.…”

Section: Experimental Protocolmentioning

confidence: 99%

“…The mechanism by which LR12 inhibits TREM-1 signaling derives from its ability to bind to the TREM-1 ligand (22). We further demonstrated that these same peptide also modulates in vivo the inflammatory cascade triggered by infection, thus inhibiting hyperresponsiveness, organ damage, and death during sepsis in mice (22).…”

mentioning

confidence: 90%

Effects of a TREM-Like Transcript 1–Derived Peptide During Hypodynamic Septic Shock in Pigs

Derive¹,

Boufenzer²,

Bouazza³

et al. 2013

Shock

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The objective of this study was to determine the effects of a TREM (triggering receptor expressed on myeloid cells 1)-like transcript 1-derived peptide (LR12) administration during septic shock in pigs. Two hours after induction of a fecal peritonitis, anesthetized and mechanically ventilated adult male minipigs were randomized to receive LR12 (n = 6) or its vehicle alone (normal saline, n = 5). Two animals were operated and instrumented without the induction of peritonitis and served as controls (sham). Resuscitation was achieved using hydroxyethyl starch (up to 20 mL/kg) and norepinephrine infusion (up to 10 μg/kg per minute). Hemodynamic parameters were continuously recorded. Gas exchange, acid-base status, organ function, and plasma cytokines concentrations were evaluated at regular intervals until 24 h after the onset of peritonitis when animals were killed under anesthesia. Peritonitis induced profound hypotension, myocardial dysfunction, lactic acidosis, coagulation abnormalities, and multiple organ failure. These disorders were largely attenuated by LR12. In particular, cardiovascular failure was dampened as attested by a better mean arterial pressure, cardiac index, cardiac power index, and S(v)O(2), despite lower norepinephrine requirements. LR12, a TREM-like transcript 1-derived peptide, exhibits salutary properties during septic shock in adult minipigs.

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“…In general, expression of TREM-1 is upregulated through stimulation with TLR agonists and cytokines [9]. Endogenous ligands for TREM-1 have been observed on PMN and platelets as well as in the sera of septic patients [10,11,12,13]. However, the exact nature of the TREM-1 ligand and cell-specific function of the TREM-1 receptor have so far remained elusive.…”

Section: Introductionmentioning

confidence: 99%

Distinct Signaling Cascades of TREM-1, TLR and NLR in Neutrophils and Monocytic Cells

Prüfer

Weber²,

Sasca³

et al. 2013

J Innate Immun

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Triggering receptor expressed on myeloid cells 1 (TREM-1) is an important mediator of innate inflammatory responses in microbial infections and sepsis. TREM-1 ligation on neutrophils (PMN) or monocytes results in the production of proinflammatory cytokines. Engagement of TREM-1 induces the activation of MAP kinases as well as rapid Ca²⁺ mobilization. However, a detailed understanding of TREM-1 signaling pathways is currently lacking. We evaluated the TREM-1 signaling hierarchy in monocytic cells and found that the acute myeloid leukemia cell line MUTZ-3 expresses TREM-1 in a natural and functional manner. We compared essential signaling molecules of the TREM-1, TLR and NLR cascade in MUTZ-3 cells as well as primary monocytes or PMN by Western blot analysis. These studies confirmed the essential role of phosphatidyl inositide 3-kinase (PI3K) and p38MAPK in the TREM-1 as well as the TLR or NLR cascade of monocytic cells. Importantly, PI3K and p38MAPK signals in monocytic cells both control Ca²⁺ mobilization and are directly connected in the TREM-1 signaling hierarchy, which contrasts previous results obtained in PMN. Taken together, our results indicate cell type-specific differences in the TREM-1 signaling cascade and contribute to an enhanced understanding of the regulation of innate inflammatory responses.

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Soluble Trem-like Transcript-1 Regulates Leukocyte Activation and Controls Microbial Sepsis

Cited by 102 publications

References 32 publications

TREM-1 Mediates Inflammatory Injury and Cardiac Remodeling Following Myocardial Infarction

TREM-1 Mediates Inflammatory Injury and Cardiac Remodeling Following Myocardial Infarction

Effects of a TREM-Like Transcript 1–Derived Peptide During Hypodynamic Septic Shock in Pigs

Distinct Signaling Cascades of TREM-1, TLR and NLR in Neutrophils and Monocytic Cells

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