Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
J Cell Biol. 2012 Aug 20;198(4):561-74. doi: 10.1083/jcb.201111136.
Human and murine platelets (PLTs) variably express toll-like receptors (TLRs), which link the innate and adaptive immune responses during infectious inflammation and atherosclerotic vascular disease. In this paper, we show that the TLR9 transcript is specifically up-regulated during pro-PLT production and is distributed to a novel electron-dense tubular system-related compartment we have named the T granule. TLR9 colocalizes with protein disulfide isomerase and is associated with either VAMP 7 or VAMP 8, which regulates its distribution in PLTs on contact activation (spreading). Preincubation of PLTs with type IV collagen specifically increased TLR9 and CD62P surface expression and augmented oligodeoxynucleotide (ODN) sequestration and PLT clumping upon addition of bacterial/viral ODNs. Collectively, this paper (a) tracks TLR9 to a new intracellular compartment in PLTs and (b) describes a novel mechanism of TLR9 organization and signaling in human PLTs.
人源和鼠源血小板（PLT）可表达 Toll 样受体（TLR），在感染性炎症和动脉粥样硬化性血管疾病期间，TLR 连接固有免疫和适应性免疫反应。在本文中，我们表明 TLR9 转录本在促血小板生成过程中特异性地上调，并分布到我们命名为 T 颗粒的新型电子致密管状系统相关隔室。TLR9 与蛋白二硫键异构酶共定位，并与 VAMP7 或 VAMP8 相关，后者调节其在血小板接触激活（铺展）时的分布。PLT 与 IV 型胶原的预孵育可特异性地增加 TLR9 和 CD62P 的表面表达，并在加入细菌/病毒 ODN 时增强 ODN 捕获和 PLT 聚集。总的来说，本文（a）将 TLR9 追踪到 PLT 的一个新的细胞内隔室，（b）描述了人源 PLT 中 TLR9 组织和信号转导的新机制。
