Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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

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


  • Washington AV
  • Gibot S
  • Acevedo I
  • Gattis J
  • Quigley L
  • Feltz R
  • De La Mota A
  • Schubert RL
  • Gomez-Rodriguez J
  • Cheng J
  • Dutra A
  • Pak E
  • Chertov O
  • Rivera L
  • Morales J
  • Lubkowski J
  • Hunter R
  • Schwartzberg PL
  • McVicar DW


The Journal of clinical investigation

Publication Data

June 2, 2009

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:

Mesh Terms

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