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Blood, 15 August 2004, Vol. 104, No. 4, pp. 1042-1047.
Prepublished online as a Blood First Edition Paper on April 20, 2004; DOI 10.1182/blood-2004-01-0315.


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Submitted January 28, 2004
Accepted April 2, 2004

TREM Family Member, TLT-1, Is Found Exclusively in the {alpha}-granules of Megakaryocytes and Platelets

A V Washington, Rebecca L Schubert, Laura Quigley, Theresa Disipio, Robert Feltz, Edward H Cho, and Daniel W McVicar*

Laboratory of Experimental Immunology, National Cancer Institute-Frederick, Frederick, MD, USA
Immage Analysis Laboratory, SAIC-Frederick, Frederick, MD, USA

* Corresponding author; email: mcvicar{at}nih.gov.

The Triggering Receptors Expressed on Myeloid cells (TREM) have drawn considerable attention due to their ability to activate multiple cell types within the innate immune system including neutrophils, monocyte/macrophages, and dentritic cells, via their association with DAP12. TLT-1 (TREM like transcript-1) lies within the TREM gene cluster and contains the characteristic single V-set Ig domain of the family, but its longer cytoplasmic tail is comprised of both a proline rich region and an immune receptor tyrosine-based inhibitory motif, the latter known to be used for interactions with protein tyrosine phosphatases. Here, we report that TLT-1 is expressed exclusively in platelets and megakaryocytes (MK), and that TLT-1 expression is upregulated dramatically upon platelet activation. Consistent with this observation, confocal microscopy demonstrates that TLT-1 is prepackaged, along with CD62P, into both MK and platelet {alpha}-granules. Differences in thrombin-induced redistribution of CD62P and TLT-1 indicate that TLT-1 is not simply cargo of {alpha}-granules, but may instead regulate granule construction or dispersal. Together these data show that that TLT-1 does not function to inhibit members of the TREM family but instead plays a role in maintaining vascular hemostasis and regulating coagulation and inflammation at sites of injury.


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