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T granules in human platelets function in TLR9 organization and signaling

Thon, Jonathan N; Peters, Christopher G; Machlus, Kellie R; Aslam, Rukhsana; Rowley, Jesse; Macleod, Hannah; Devine, Matthew T; Fuchs, Tobias A; Weyrich, Andrew S and Semple, John W LU , et al. (2012) In Journal of Cell Biology 198(4). p.74-561
Abstract

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... (More)

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.

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keywords
Animals, Atherosclerosis, Blood Platelets, Cell Compartmentation, Cytoplasmic Granules, Erythroid Precursor Cells, Humans, Mice, Platelet Activation, Signal Transduction, Thrombopoiesis, Toll-Like Receptor 9, Up-Regulation, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
in
Journal of Cell Biology
volume
198
issue
4
pages
14 pages
publisher
Rockefeller University Press
external identifiers
  • scopus:84866407700
ISSN
0021-9525
DOI
10.1083/jcb.201111136
language
English
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no
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9ce32c02-a79e-4f4a-ae2a-843665cd4ba2
date added to LUP
2016-09-23 12:03:03
date last changed
2017-03-26 04:45:22
@article{9ce32c02-a79e-4f4a-ae2a-843665cd4ba2,
  abstract     = {<p>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.</p>},
  author       = {Thon, Jonathan N and Peters, Christopher G and Machlus, Kellie R and Aslam, Rukhsana and Rowley, Jesse and Macleod, Hannah and Devine, Matthew T and Fuchs, Tobias A and Weyrich, Andrew S and Semple, John W and Flaumenhaft, Robert and Italiano, Joseph E},
  issn         = {0021-9525},
  keyword      = {Animals,Atherosclerosis,Blood Platelets,Cell Compartmentation,Cytoplasmic Granules,Erythroid Precursor Cells,Humans,Mice,Platelet Activation,Signal Transduction,Thrombopoiesis,Toll-Like Receptor 9,Up-Regulation,Journal Article,Research Support, N.I.H., Extramural,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {08},
  number       = {4},
  pages        = {74--561},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Cell Biology},
  title        = {T granules in human platelets function in TLR9 organization and signaling},
  url          = {http://dx.doi.org/10.1083/jcb.201111136},
  volume       = {198},
  year         = {2012},
}