Coated platelets function in platelet-dependent fibrin formation via integrin αIIbβ3 and transglutaminase factor XIII

Nadine J A Mattheij, Frauke Swieringa, Tom G. Mastenbroek, Michelle A. Berny-Lang, Frauke May, Constance C F M J Baaten, Paola E J van der Meijden, Yvonne M C Henskens, Erik A M Beckers, Dennis P L Suylen, Marc W. Nolte, Tilman M. Hackeng, Owen McCarty, Johan W M Heemskerk, Judith M E M Cosemans

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Abstract

Coated platelets, formed by collagen and thrombin activation, have been characterized in different ways: i) by the formation of a protein coat of α-granular proteins; ii) by exposure of procoagulant phosphatidylserine; or iii) by high fibrinogen binding. Yet, their functional role has remained unclear. Here we used a novel transglutaminase probe, Rhod-A14, to identify a subpopulation of platelets with a cross-linked protein coat, and compared this with other platelet subpopulations using a panel of functional assays. Platelet stimulation with convulxin/ thrombin resulted in initial integrin αIIbb3 activation, the appearance of a platelet population with high fibrinogen binding, (independently of active integrins, but dependent on the presence of thrombin) followed by phosphatidylserine exposure and binding of coagulation factors Va and Xa. A subpopulation of phosphatidylserine-exposing platelets bound Rhod-A14 both in suspension and in thrombi generated on a collagen surface. In suspension, high fibrinogen and Rhod-A14 binding were antagonized by combined inhibition of transglutaminase activity and integrin αIIbb3. Markedly, in thrombi from mice deficient in transglutaminase factor XIII, platelet-driven fibrin formation and Rhod- A14 binding were abolished by blockage of integrin αIIbβ3. Vice versa, star-like fibrin formation from platelets of a patient with deficiency in αIIbβ3 (Glanzmann thrombasthenia) was abolished upon blockage of transglutaminase activity. We conclude that coated platelets, with initial αIIbβ3 activation and high fibrinogen binding, form a subpopulation of phosphatidylserine-exposing platelets, and function in platelet-dependent star-like fibrin fiber formation via transglutaminase factor XIII and integrin αIIbβ3.

Original languageEnglish (US)
Pages (from-to)427-436
Number of pages10
JournalHaematologica
Volume101
Issue number4
DOIs
StatePublished - Mar 31 2016

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Factor XIII
Transglutaminases
Fibrin
Integrins
Blood Platelets
Phosphatidylserines
Fibrinogen
Thrombin
Capsid Proteins
Suspensions
Thrombosis
Collagen
Factor Va
Thrombasthenia

ASJC Scopus subject areas

  • Hematology

Cite this

Mattheij, N. J. A., Swieringa, F., Mastenbroek, T. G., Berny-Lang, M. A., May, F., Baaten, C. C. F. M. J., ... Cosemans, J. M. E. M. (2016). Coated platelets function in platelet-dependent fibrin formation via integrin αIIbβ3 and transglutaminase factor XIII. Haematologica, 101(4), 427-436. https://doi.org/10.3324/haematol.2015.131441

Coated platelets function in platelet-dependent fibrin formation via integrin αIIbβ3 and transglutaminase factor XIII. / Mattheij, Nadine J A; Swieringa, Frauke; Mastenbroek, Tom G.; Berny-Lang, Michelle A.; May, Frauke; Baaten, Constance C F M J; van der Meijden, Paola E J; Henskens, Yvonne M C; Beckers, Erik A M; Suylen, Dennis P L; Nolte, Marc W.; Hackeng, Tilman M.; McCarty, Owen; Heemskerk, Johan W M; Cosemans, Judith M E M.

In: Haematologica, Vol. 101, No. 4, 31.03.2016, p. 427-436.

Research output: Contribution to journalArticle

Mattheij, NJA, Swieringa, F, Mastenbroek, TG, Berny-Lang, MA, May, F, Baaten, CCFMJ, van der Meijden, PEJ, Henskens, YMC, Beckers, EAM, Suylen, DPL, Nolte, MW, Hackeng, TM, McCarty, O, Heemskerk, JWM & Cosemans, JMEM 2016, 'Coated platelets function in platelet-dependent fibrin formation via integrin αIIbβ3 and transglutaminase factor XIII', Haematologica, vol. 101, no. 4, pp. 427-436. https://doi.org/10.3324/haematol.2015.131441
Mattheij, Nadine J A ; Swieringa, Frauke ; Mastenbroek, Tom G. ; Berny-Lang, Michelle A. ; May, Frauke ; Baaten, Constance C F M J ; van der Meijden, Paola E J ; Henskens, Yvonne M C ; Beckers, Erik A M ; Suylen, Dennis P L ; Nolte, Marc W. ; Hackeng, Tilman M. ; McCarty, Owen ; Heemskerk, Johan W M ; Cosemans, Judith M E M. / Coated platelets function in platelet-dependent fibrin formation via integrin αIIbβ3 and transglutaminase factor XIII. In: Haematologica. 2016 ; Vol. 101, No. 4. pp. 427-436.
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AU - Berny-Lang, Michelle A.

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AU - Baaten, Constance C F M J

AU - van der Meijden, Paola E J

AU - Henskens, Yvonne M C

AU - Beckers, Erik A M

AU - Suylen, Dennis P L

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