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Toll-like receptor 2 stimulation of platelets is mediated by purinergic P2X(1)-dependent Ca2+ mobilisation, cyclooxygenase and purinergic P2Y(1) and P2Y(12) receptor activation
Örebro University, School of Health and Medical Sciences. Fac Hlth Sci, Linkoping Univ, Linkoping, Sweden.
Fac Hlth Sci, Linkoping Univ, Linkoping, Sweden.
Fac Hlth Sci, Linkoping Univ, Linkoping, Sweden.
Fac Hlth Sci, Linkoping Univ, Linkoping, Sweden.
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2010 (English)In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 103, no 2, p. 398-407Article in journal (Refereed) Published
Abstract [en]

Toll-like receptor 2 (TLR2), which recognise and respond to conserved microbial pathogen-associated molecular patterns, is expressed on the platelet surface. Furthermore, it has recently been shown that the TLR2/1 agonist Pam(3)CSK(4) stimulates platelet activation. The aim of the present study was to clarify important signalling events in Pam(3)CSK(4)-induced platelet aggregation and secretion. Platelet interaction with Pam(3)CSK(4) and the TLR2/6 agonist MALP-2 was studied by analysing aggregation, ATP-secretion, [Ca2+](i) mobilisation and thromboxane B2 (TxB(2)) production. The results show that Pam(3)CSK(4) but not MALP-2 induces [Ca2+](i) increase, TxB(2) production, dense granule secretion and platelet aggregation. Preincubation of platelets with MALP-2 inhibited the Pam(3)CSK(4)-induced responses. The ATP-secretion and aggregation in Pam(3)CSK(4)-stimulated platelets was impeded by the purinergic P2X(1) inhibitor MRS 2159, the purinergic P2Y(1) and P2Y(12) antagonists MRS 2179 and cangrelor, the phospholipase C inhibitor U73122, the calcium chelator BAPT-AM and aspirin. The calcium mobilisation was lowered by MRS 2159, aspirin and U73122 whereas the TxB(2) production was antagonised by MRS 2159, aspirin and BAPT-AM. When investigating the involvement of the myeloid differentiation factor-88 (MyD88) -dependent pathway, we found that platelets express MyD88 and interleukin 1 receptor-associated kinase (IRAK-1), which are proteins important in TLR signalling. However, Pam(3)CSK(4) did not stimulate a rapid (within 10 minutes) phosphorylation of IRAK-1 in platelets. In conclusion, the results show that Pam(3)CSK(4)-induced platelet aggregation and secretion depends on a P2X(1)-mediated Ca2+ mobilisation, production of TxA(2) and ADP receptor activation. The findings in this study further support a role for platelets in sensing bacterial components.

Place, publisher, year, edition, pages
2010. Vol. 103, no 2, p. 398-407
Keywords [en]
Infection, purinergic P2X(1) receptor, atherosclerosis, MALP-2, Pam(3)CSK(4), platelet, MyD88, IRAK-1
National Category
Medical and Health Sciences
Research subject
Biomedicine; Medicine
Identifiers
URN: urn:nbn:se:oru:diva-13010DOI: 10.1160/TH09-07-0442ISI: 000274734100022OAI: oai:DiVA.org:oru-13010DiVA, id: diva2:382820
Available from: 2011-01-03 Created: 2011-01-03 Last updated: 2018-04-20Bibliographically approved

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Kälvegren, HannaBengtsson, Torbjörn

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