T granules in human platelets function in TLR9 organization and signaling
(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.
(Less)
- author
- publishing date
- 2012-08-20
- type
- Contribution to journal
- publication status
- published
- 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
- pmid:22908309
- ISSN
- 0021-9525
- DOI
- 10.1083/jcb.201111136
- language
- English
- LU publication?
- no
- id
- 9ce32c02-a79e-4f4a-ae2a-843665cd4ba2
- date added to LUP
- 2016-09-23 12:03:03
- date last changed
- 2024-09-07 21:40:48
@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}}, 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}}, 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}}, doi = {{10.1083/jcb.201111136}}, volume = {{198}}, year = {{2012}}, }