T granules in human platelets function in TLR9 organization and signaling
T granules in human platelets function in TLR9 organization and signaling
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DOI：
10.1083/jcb.201111136
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发表时间：
2012-08-20
影响因子：
7.8
通讯作者：
Italiano, Joseph E., Jr.
中科院分区：
文献类型：
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作者：
Thon, Jonathan N.;Peters, Christopher G.;Italiano, Joseph E., Jr.
人类和小鼠血小板（PLTs）表达toll样受体（TLRs）， TLRs在感染性炎症和动脉粥样硬化性血管疾病期间连接先天和适应性免疫反应。在本文中，我们发现TLR9转录本在pro-PLT产生过程中被特异性上调，并分布到一种新的电子致密管状系统相关的室中，我们将其命名为T颗粒。TLR9与蛋白二硫异构酶共定位，并与VAMP 7或VAMP 8相关，在接触激活（扩散）时调节其在plt中的分布。IV型胶原预孵育的PLT特异性地增加了TLR9和CD62P表面表达，增加了寡脱氧核苷酸（ODN）的分离和添加细菌/病毒ODN后PLT的聚集。总的来说，本文(a)追踪TLR9到plt中一个新的细胞内区室，(b)描述了TLR9在人类plt中的组织和信号传导的新机制。
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 oligodeoxy-nucleotide (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.