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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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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

A TREM family member, TLT-1, is found exclusively in the {alpha}-granules of megakaryocytes and platelets

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

From the Laboratory of Experimental Immunology and The Image Analysis Laboratory, Science Application International Corporation Frederick, National Cancer Institute (NCI)–Frederick, MD.

The triggering receptors expressed on myeloid cells (TREMs) have drawn considerable attention due to their ability to activate multiple cell types within the innate immune system, including neutrophils, monocyte/macrophages, and dendritic 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 immunoglobulin (Ig) domain of the family, but its longer cytoplasmic tail is composed 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 (MKs) and that TLT-1 expression is up-regulated 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 may play a role in maintaining vascular hemostasis and regulating coagulation and inflammation at sites of injury.


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