Washington A Valance, Schubert Rebecca L, Quigley Laura, Disipio Theresa, Feltz Robert, Cho Edward H, McVicar Daniel W
NCI-Frederick, 560/Rm 31-46, Frederick, MD 21702, USA.
Blood. 2004 Aug 15;104(4):1042-7. doi: 10.1182/blood-2004-01-0315. Epub 2004 Apr 20.
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.
髓系细胞表达的触发受体（TREMs）因其能够通过与DAP12结合激活先天性免疫系统中的多种细胞类型（包括中性粒细胞、单核细胞/巨噬细胞和树突状细胞）而备受关注。TLT-1（TREM样转录本-1）位于TREM基因簇内，包含该家族特有的单个V-set免疫球蛋白（Ig）结构域，但其较长的胞质尾由富含脯氨酸的区域和基于免疫受体酪氨酸的抑制基序组成，后者已知用于与蛋白酪氨酸磷酸酶相互作用。在此我们报告，TLT-1仅在血小板和巨核细胞（MKs）中表达，并且在血小板激活后TLT-1表达显著上调。与此观察结果一致，共聚焦显微镜显示TLT-1与CD62P一起预先包装在MK和血小板α-颗粒中。凝血酶诱导的CD62P和TLT-1再分布的差异表明，TLT-1不仅仅是α-颗粒的货物，反而可能调节颗粒的构建或分散。这些数据共同表明，TLT-1并非起到抑制TREM家族成员的作用，而是可能在维持血管止血以及调节损伤部位的凝血和炎症中发挥作用。
