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TREM-like transcript-1 protects against inflammation-associated hemorrhage by facilitating platelet aggregation in mice and humans.

http://www.ncbi.nlm.nih.gov/pubmed/19436112

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.

Pubmed ID: 19436112 RIS Download

Mesh terms: Animals | Fibrinogen | Hemorrhage | Humans | Inflammation | Lipopolysaccharides | Mice | Mice, Inbred C57BL | Mice, Knockout | Platelet Aggregation | Protein Binding | Receptors, Immunologic | Recombinant Proteins | Sepsis | Solubility

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Associated grants

  • Agency: NCRR NIH HHS, Id: 2G12RR3035
  • Agency: NCI NIH HHS, Id: N01-CO-12400
  • Agency: NIGMS NIH HHS, Id: SC2GM081237
  • Agency: Intramural NIH HHS, Id:

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