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

  1. Author:
    Washington, A. V.
    Gibot, S.
    Acevedo, I.
    Gattis, J.
    Quigley, L.
    Feltz, R.
    De La Mota, A.
    Schubert, R. L.
    Gomez-Rodriguez, J.
    Cheng, J.
    Dutra, A.
    Pak, E.
    Chertov, O.
    Rivera, L.
    Morales, J.
    Lubkowski, J.
    Hunter, R.
    Schwartzberg, P. L.

  2. Author Address

    Washington, A. Valance, Quigley, Laura, Feltz, Robert, Schubert, Rebecca L.; McVicar, Daniel W.] NCI, Canc & Inflammat Program, Ft Detrick, MD 21702 USA. [Washington, A. Valance, Acevedo, Ismael, De La Mota, Alina, Rivera, Linette, Morales, Jessica, Hunter, Robert] Univ Cent Caribe, Lab Anat & Cell Biol, Bayamon, PR USA. [Gibot, Sebastien] Hop Cent, Serv Reanimat Med, Nancy, France. [Gibot, Sebastien] Nancy Univ, Fac Med, Contrat Avenir INSERM, Grp Choc, Nancy, France. [Gattis, James, Lubkowski, Jacek] NCI, Macromol Crystallog Lab, NIH, Frederick, MD 21701 USA. [Gomez-Rodriguez, Julio, Cheng, Jun, Dutra, Amalia, Pak, Evgenia, Schwartzberg, Pamela L.] NHGRI, NIH, Bethesda, MD 20892 USA. [Chertov, Oleg] SAIC Frederick Inc, NCI, Adv Technol Program, Prot Chem Lab, Frederick, MD USA.
    1. Year: 2009
  2. Journal: Journal of Clinical Investigation
    1. 119
    2. 6
    3. Pages: 1489-1501
  4. Type of Article: Article
  1. 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 a-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.

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  2. DOI: 10.1172/jci36175
  3. PMID: 19436112

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