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Published on: May 2, 2018
Soluble TREM-like transcript-1 regulates leukocyte activation and controls microbial sepsis
Marc Derive1, Youcef Bouazza, Nacira Sennoun
1Groupe Choc, Contrat Avenir INSERM, Faculté de Médecine, Nancy Université, 54000 Nancy, France.
Journal of Immunology (Baltimore, Md. : 1950)
|May 4, 2012
Summary
Platelet-derived soluble triggering receptor expressed on myeloid cells-like transcript-1 (TLT-1) dampens inflammation during sepsis. A specific sequence (LR17) regulates leukocyte activation and improves survival in septic mice, offering new therapeutic avenues.
Area of Science:
- Immunology
- Hematology
- Sepsis Pathophysiology
Background:
- Triggering receptor expressed on myeloid cells (TREM)-1 amplifies immune response in sepsis.
- TREM-like transcript-1 (TLT-1) is expressed on activated platelets and mediates aggregation.
- Soluble TLT-1's role in inflammation and sepsis is not fully understood.
Purpose of the Study:
- To investigate the role of soluble TLT-1 in regulating inflammation during sepsis.
- To identify the functional domain of TLT-1 responsible for its anti-inflammatory effects.
- To explore the therapeutic potential of TLT-1 in sepsis models.
Main Methods:
- Treatment of septic mice with soluble TLT-1 or its derived peptide (LR17).
- Assessment of survival rates and inflammatory markers in treated and control groups.
- Analysis of leukocyte activation and platelet-neutrophil interactions.
Main Results:
- Soluble TLT-1 dampens leukocyte activation and modulates platelet-neutrophil crosstalk in sepsis.
- A 17-amino acid sequence (LR17) of TLT-1's extracellular domain mediates this regulatory activity.
- Early or late administration of LR17 significantly improved survival in septic mice.
- TREM-1 ligand competition by LR17 was identified as the mechanism of action.
Conclusions:
- Platelet-derived soluble TLT-1 is a key endogenous regulator of sepsis-associated inflammation.
- The LR17 peptide represents a potential therapeutic agent for sepsis.
- Soluble TLT-1 may also play a role in noninfectious inflammatory disorders.
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