Soluble TREM-like transcript-1 regulates leukocyte activation and controls microbial sepsis.
Soluble TREM-like transcript-1 regulates leukocyte activation and controls microbial sepsis.
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DOI：
10.4049/jimmunol.1102674
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发表时间：
2012-06-01
期刊：
影响因子：
--
通讯作者：
Gibot S
中科院分区：
文献类型：
--
作者：
Derive M;Bouazza Y;Sennoun N;Marchionni S;Quigley L;Washington V;Massin F;Max JP;Ford J;Alauzet C;Levy B;McVicar DW;Gibot S
髓样细胞上表达的触发受体（TREM）-1通过放大宿主免疫应答在脓毒症发作期间起关键作用。TREM样转录物-1（TLT-1）属于TREM家族，在活化的血小板上选择性表达，并且已知通过结合纤维蛋白原促进血小板聚集。在这项研究中，我们表明，可溶性形式的TLT-1涉及在脓毒症的炎症调节过程中，通过抑制白细胞活化和调节血小板-中性粒细胞串扰。TLT-1细胞外结构域（LR 17）的17-aa序列通过与TREM-1配体竞争而负责该活性。早期或晚期LR 17治疗脓毒症小鼠可以提高存活率，而treml-1−/−动物对多种微生物感染高度敏感。目前的研究结果确定血小板衍生的可溶性TLT-1作为脓毒症相关炎症的有效内源性调节剂，并开辟了新的治疗前景。我们预期可溶性TLT-1在其他非感染性炎症性疾病中调节白细胞活化方面是重要的。
The triggering receptor expressed on myeloid cells (TREM)-1 plays a crucial role during the onset of sepsis by amplifying the host immune response. The TREM-like transcript-1 (TLT-1) belongs to the TREM family, is selectively expressed on activated platelets, and is known to facilitate platelet aggregation through binding to fibrinogen. In this study, we show that a soluble form of TLT-1 is implicated in the regulation of inflammation during sepsis by dampening leukocyte activation and modulating platelet-neutrophil crosstalk. A 17-aa sequence of the TLT-1 extracellular domain (LR17) is responsible for this activity through competition with the TREM-1 ligand. Whereas early or late LR17 treatment of septic mice improves survival, treml-1−/− animals are highly susceptible to polymicrobial infection. The present findings identify platelet-derived soluble TLT-1 as a potent endogenous regulator of sepsisassociated inflammation and open new therapeutic perspectives. We anticipate soluble TLT-1 to be important in regulating leukocyte activation during other noninfectious inflammatory disorders.
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影响因子：
15.3
作者：
Gibot, S;Kolopp-Sarda, MN;Béné, MC;Bollaert, PE;Lozniewski, A;Mory, F;Levy, B;Faure, GC
通讯作者：
Faure, GC
影响因子：
3.1
作者：
Gibot, S;Buonsanti, C;Lévy, B
通讯作者：
Lévy, B
影响因子：
120.7
作者：
LEGALL, JR;LEMESHOW, S;SAULNIER, F
通讯作者：
SAULNIER, F
影响因子：
4.8
作者：
Gattis, JL;Washington, AV;Lubkowski, J
通讯作者：
Lubkowski, J
影响因子：
2.2
作者：
George, TC;Fanning, SL;Lynch, DH
通讯作者：
Lynch, DH