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TREM-like transcript-1 protects against inflammation-associated hemorrhage by facilitating platelet aggregation in mice and humans.
- Source :
-
Journal of Clinical Investigation . Jun2009, Vol. 119 Issue 6, p1489-1501. 13p. 1 Color Photograph, 1 Diagram, 8 Graphs. - Publication Year :
- 2009
-
Abstract
- Triggering receptor expressed on myeloid cells-like (TREM-like) transcript-1 (TLT-1), a type 1 single Ig domain orphan receptor specific to platelet and megakaryocyte alpha-granules, relocates to the platelet surface upon platelet stimulation. We found here that patients diagnosed with sepsis, in contrast to healthy individuals, had substantial levels of soluble TLT-1 (sTLT-1) in their plasma that correlated with the presence of disseminated intravascular coagulation. sTLT-1 bound to fibrinogen and augmented platelet aggregation in vitro. Furthermore, the cytoplasmic domain of TLT-1 could also bind ezrin/radixin/moesin family proteins, suggesting its ability to link fibrinogen to the platelet cytoskeleton. Accordingly, platelets of Treml1-/- mice failed to aggregate efficiently, extending tail-bleeding times. Lipopolysaccharide-treated Treml1-/- mice developed higher plasma levels of TNF and D-dimers than wild-type mice and were more likely to succumb during challenge. Finally, Treml1-/- mice were predisposed to hemorrhage associated with localized inflammatory lesions. Taken together, our findings suggest that TLT-1 plays a protective role during inflammation by dampening the inflammatory response and facilitating platelet aggregation at sites of vascular injury. Therefore, therapeutic modulation of TLT-1-mediated effects may provide clinical benefit to patients with hypercoagulatory conditions, including those associated with inflammation. [ABSTRACT FROM AUTHOR]
- Subjects :
- *INFLAMMATION
*HEMORRHAGE
*BLOOD platelets
*MEGAKARYOCYTES
*SEPSIS
*FIBRINOGEN
*LABORATORY mice
*HEMORRHAGE complications
*ANIMAL experimentation
*BLOOD platelet aggregation
*CELL receptors
*COMPARATIVE studies
*RESEARCH methodology
*MEDICAL cooperation
*MICE
*RECOMBINANT proteins
*RESEARCH
*RESEARCH funding
*SOLUBILITY
*EVALUATION research
*LIPOPOLYSACCHARIDES
*BLOOD
*DISEASE complications
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 119
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- 41522147
- Full Text :
- https://doi.org/10.1172/JCI36175