Gray platelet syndrome and defective thrombo-inflammation in Nbeal2-deficient mice

B3 ECKES KRIEGDeppermann C, Cherpokova D, Nurden P, Schulz JN, Thielmann I, Kraft P, Vögtle T, Kleinschnitz C, Dütting S, Krohne G, Eming SA, Nurden AT, Eckes B, Stoll G, Stegner D, Nieswandt B; J Clin Invest. 2013 Jul 1. pii: 69210. doi: 10.1172/JCI69210. [Epub ahead of print]

Abstract

Platelets are anuclear organelle-rich cell fragments derived from bone marrow megakaryocytes (MKs) that safeguard vascular integrity. The major platelet organelles, ?-granules, release proteins that participate in thrombus formation and hemostasis. Proteins stored in ?-granules are also thought to play a role in inflammation and wound healing, but their functional significance in vivo is unknown. Mutations in NBEAL2 have been linked to gray platelet syndrome (GPS), a rare bleeding disorder characterized by macrothrombocytopenia, with platelets lacking ?-granules. Here we show that Nbeal2-knockout mice display the characteristics of human GPS, with defective ?-granule biogenesis in MKs and their absence from platelets. Nbeal2 deficiency did not affect MK differentiation and proplatelet formation in vitro or platelet life span in vivo. Nbeal2-deficient platelets displayed impaired adhesion, aggregation, and coagulant activity ex vivo that translated into defective arterial thrombus formation and protection from thrombo-inflammatory brain infarction following focal cerebral ischemia. In a model of excisional skin wound repair, Nbeal2-deficient mice exhibited impaired development of functional granulation tissue due to severely reduced differentiation of myofibroblasts in the absence of ?-granule secretion. This study demonstrates that platelet ?-granule constituents are critically required not only for hemostasis but also thrombosis, acute thrombo-inflammatory disease states, and tissue reconstitution after injury.

Pubmed

  • News

  • Upcoming Events

    There are no upcoming events at this time.

  • December 2020
    M T W T F S S
     123456
    78910111213
    14151617181920
    21222324252627
    28293031  

© 2017 SFB 829

Durch die weitere Nutzung der Seite stimmst du der Verwendung von Cookies zu. Weitere Informationen

Die Cookie-Einstellungen auf dieser Website sind auf "Cookies zulassen" eingestellt, um das beste Surferlebnis zu ermöglichen. Wenn du diese Website ohne Änderung der Cookie-Einstellungen verwendest oder auf "Akzeptieren" klickst, erklärst du sich damit einverstanden.

Schließen