IkB kinase 2 is not essential for platelet activation

Manuel Salzmann, Sonja Bleichert, Bernhard Moser, Marion Mussbacher, Mildred Haase, Bastian Hoesel, Waltraud C Schrottmaier, Julia B Kral-Pointner, Makoto Itakura, Katy Schmidt, Alice Assinger, Johannes A Schmid

Research output: Journal article (peer-reviewed)Journal article

2 Citations (Scopus)

Abstract

Platelets are small anucleate cells that release a plethora of molecules to ensure functional hemostasis. It has been reported that IkB kinase 2 (IKK2), the central enzyme of the inflammatory NF-kB pathway, is involved in platelet activation, because megakaryocyte/platelet-specific deletion of exons 6 and 7 of IKK2 resulted in platelet degranulation defects and prolonged bleeding. We aimed to investigate the role of IKK2 in platelet physiology in more detail, using a platelet-specific IKK2 knockout via excision of exon 3, which makes up the active site of the enzyme. We verified the deletion on genomic and transcriptional levels in megakaryocytes and were not able to detect any residual IKK2 protein; however, platelets from these mice did not show any functional impairment in vivo or in vitro. Bleeding time and thrombus formation were not affected in platelet-specific IKK2-knockout mice. Moreover, platelet aggregation, glycoprotein GPIIb/IIIa activation, and degranulation were unaltered. These observations were confirmed by pharmacological inhibition of IKK2 with TPCA-1 and BMS-345541, which did not affect activation of murine or human platelets over a wide concentration range. Altogether, our results imply that IKK2 is not essential for platelet function.

Original languageEnglish
Pages (from-to)638-643
Number of pages6
JournalBlood advances
Volume4
Issue number4
DOIs
Publication statusPublished - 25 Feb 2020
Externally publishedYes

Keywords

  • Animals
  • Blood Platelets
  • I-kappa B Kinase/genetics
  • Mice
  • Platelet Activation
  • Platelet Aggregation
  • Platelet Glycoprotein GPIIb-IIIa Complex

ASJC Scopus subject areas

  • Hematology

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