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Hamostaseologie 2018; 38(04): 211-222
DOI: 10.1055/s-0038-1675149
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Platelet Signaling in Primary Haemostasis and Arterial Thrombus Formation: Part 2

Rüdiger E. Scharf
1   Division of Clinical and Experimental Haemostasis, Hemotherapy and Transfusion Medicine, University Blood Center, and Haemophilia Comprehensive Care Center, Institute of Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University Medical Center, Düsseldorf, Germany
2   Biological Medical Research Center, Heinrich Heine University, Düsseldorf, Germany
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Further Information

Publication History

13 April 2018

18 September 2018

Publication Date:
30 November 2018 (online)

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Abstract

Platelet signal transduction is the focus of this review. While ‘classic’ platelet signaling through G protein–coupled receptors in response to fluid-phase agonists has been extensively studied, signaling mechanisms linking platelet adhesion receptors such as GPIb-IX-V, GPVI and α2β1 to the activation of αIIbβ3 are less well established. Moreover, ‘non-haemostatic’ pathways can also activate platelets in various settings, including platelet–immune or platelet–tumour cell interactions, platelet responses to neutrophil extracellular traps, or stimulation by microbial pathogens. Genetically determined integrin variants can modulate platelet function and increase thrombogenicity. A typical example is the Pro33 (HPA-1b) variant of αIIbβ3. Recent advances in the genotype–phenotype relation of this prothrombotic variant and its impact on outside-in signaling will be reviewed.

Zusammenfassung

Thrombozytäre Prozesse der Signaltransduktion stehen im Mittelpunkt von Teil II dieser Übersicht. Die 'klassische' Signalübertragung durch G-Protein-gekoppelte Rezeptoren bei Plättchenstimulation mit diffusiblen Agonisten ist intensiv erforscht. Bislang weniger gut untersucht sind hingegen Mechanismen, die Signale thrombozytärer Adhäsionsrezeptoren wie GPIb-IX-V, GPVI und α2β1 auf αIIbβ3 übertragen und zur Aktivierung dieses Integrins führen. Weiterhin existieren 'nicht-hämostatische' Signalwege, die ebenfalls eine Plättchenaktivierung auslösen können. Hierzu zählen Thrombozyteninteraktionen mit Immun- oder Tumorzellen, Reaktionen auf freigesetzte Zellkernkomponenten neutrophiler Granulozyten oder Stimulation durch pathogene Keime. Genetisch determinierte Integrinvarianten können die Plättchenfunktion modulieren und die Thrombogenität erhöhen. Musterbeispiel hierfür ist die Pro33 (HPA-1b)-Variante von αIIbβ3. Jüngste Erkenntnisse zur Genotyp-Phänotyp-Beziehung dieser prothrombotischen Rezeptorvariante mit Auswirkungen auf 'Outside-in'-Signalvorgänge werden besprochen.

Keywords

platelet signaling - integrin αIIbβ3 - G protein–coupled receptors - calcium mobilization

Schlüsselwörter

Thrombozytäre Signalübertrag - Integrin αIIbβ3 - G-Protein-gekoppelte Rezeptoren - Kalziummobilisierung
 

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