Thromb Haemost 2005; 94(04): 831-838
DOI: 10.1160/TH05-01-0009
Platelets and Blood Cells
Schattauer GmbH

Agonists of toll-like receptor (TLR)2 and TLR4 are unable to modulate platelet activation by adenosine diphosphate and platelet activating factor

Jon R. Ward
1  Section of Functional Genomics, University of Sheffield, Sheffield, UK
,
Lynne Bingle
1  Section of Functional Genomics, University of Sheffield, Sheffield, UK
,
Heather M. Judge
3  Cardiovascular Research Unit, University of Sheffield, Sheffield, UK
,
Simon B. Brown
4  MRC/UoE Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
,
Robert F. Storey
3  Cardiovascular Research Unit, University of Sheffield, Sheffield, UK
,
Moira K. B. Whyte
1  Section of Functional Genomics, University of Sheffield, Sheffield, UK
,
Steven K. Dower
1  Section of Functional Genomics, University of Sheffield, Sheffield, UK
,
David J. Buttle
2  Division of Genomic Medicine, University of Sheffield, Sheffield, UK
,
Ian Sabroe
1  Section of Functional Genomics, University of Sheffield, Sheffield, UK
› Author Affiliations
Financial support:This work was supported by a British Heart Foundation PhD Studentship, and an MRC Senior Clinical Fellowship (G116/170) to I.S.
Further Information

Publication History

Received06 January 2005

Accepted after resubmission26 July 2005

Publication Date:
07 December 2017 (online)

Summary

Inappropriate platelet activation is a feature of acute and chronic diseases such as disseminated intravascular coagulation (DIC) and atherosclerosis. Since proinflammatory microbial-derived agonists can be involved in the pathogenesis of these diseases, we examined the potential role ofTLR4 (mediating responses to LPS) andTLR2 (which responds to bacterial lipopeptides) in platelet activation. Our data suggested low-level expression of TLR2 andTLR4 on platelets, determined by flow cytometry, and we also observed expression of TLR4 on a megakaryocytic cell line by both flow cytometry and immunohistochemistry. Stimulation of the platelets with the TLR4 agonist LPS, and the synthetic TLR2 agonist Pam3CSK4, resulted in no platelet aggregation, no increase in CD62P surface expression and no increase in the cytosolic concentration of Ca2+. The TLR agonists were also unable to directly activate platelets primed with epinephrine, or pretreated with a low concentration ofADP or PAF. Pretreatment of platelets with LPS or Pam3CSK4 also failed to modulate the platelet response to submaximal concentrations of the classical platelet agonists ADP and PAF. We conclude that theTLR agonists LPS and Pam3CSK4 have no direct effect on platelet activation and that platelet TLRs may be a remnant from megakaryocytes. TLR2 and TLR4 agonists are thought to have a significant role in diseases such as atherosclerosis and DIC, but our research suggests that this is through a mechanism other than direct platelet activation or by modification of platelet responses to other agonists.