Soluble TREM-like transcript-1 regulates leukocyte activation and controls microbial sepsis.
J Immunol
; 188(11): 5585-92, 2012 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-22551551
ABSTRACT
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 sepsis-associated inflammation and open new therapeutic perspectives. We anticipate soluble TLT-1 to be important in regulating leukocyte activation during other noninfectious inflammatory disorders.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Plaquetas
/
Receptores Inmunológicos
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Sepsis
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Animals
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Humans
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Male
Idioma:
En
Año:
2012
Tipo del documento:
Article