T granules in human platelets function in TLR9 organization and signaling

被引：154

作者：

Thon, Jonathan N. ^{[1
,2
]}

Peters, Christopher G. ^{[2
,6
]}

Machlus, Kellie R. ^{[1
,2
]}

Aslam, Rukhsana ^{[4
]}

Rowley, Jesse ^{[5
]}

Macleod, Hannah ^{[1
]}

Devine, Matthew T. ^{[1
]}

Fuchs, Tobias A. ^{[3
,6
,7
]}

Weyrich, Andrew S. ^{[5
]}

Semple, John W. ^{[4
]}

Flaumenhaft, Robert ^{[2
,8
]}

Italiano, Joseph E., Jr. ^{[1
,2
,9
]}

机构：

[1] Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA

[4] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Toronto Platelet Immunobiol Grp, Toronto, ON M5B 1W8, Canada

[5] Univ Utah, Program Mol Med, Salt Lake City, UT 84112 USA

[6] Immune Dis Inst, Boston, MA 02115 USA

[7] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA

[8] Beth Israel Deaconess Med Ctr, Dept Med, Div Hemostasis & Thrombosis, Boston, MA 02115 USA

[9] Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA

来源：

JOURNAL OF CELL BIOLOGY | 2012年 / 198卷 / 04期

基金：

美国国家卫生研究院;

关键词：

PROTEIN-DISULFIDE-ISOMERASE; BACTERIAL-DNA; ACTIVATED PLATELETS; BLOOD-PLATELETS; PLASMA-MEMBRANE; IN-VIVO; RECOGNITION; SURFACE; MEGAKARYOCYTES; LOCALIZATION;

D O I：

10.1083/jcb.201111136

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：561 / 574

页数：14

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