T granules in human platelets function in TLR9 organization and signaling

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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 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.

Detaljer

Författare
  • Jonathan N Thon
  • Christopher G Peters
  • Kellie R Machlus
  • Rukhsana Aslam
  • Jesse Rowley
  • Hannah Macleod
  • Matthew T Devine
  • Tobias A Fuchs
  • Andrew S Weyrich
  • John W Semple
  • Robert Flaumenhaft
  • Joseph E Italiano
Externa organisationer
  • Saint Michael's Hospital
Forskningsområden

Nyckelord

Originalspråkengelska
Sidor (från-till)561-74
Antal sidor14
TidskriftJournal of Cell Biology
Volym198
Utgåva nummer4
StatusPublished - 2012 aug 20
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa