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Hamostaseologie 2015; 35(03): 244-251
DOI: 10.5482/HAMO-14-11-0071
Review
Schattauer GmbH

Platelets and vascular inflammation of the brain

Thrombozyten und neurovaskuläre Inflammation
M. Mezger
1   University Clinic for Cardiovascular Medicine, University of Tuebingen, Germany
2   Section for Cardioimmunology, University of Tuebingen, Germany
,
K. Göbel
3   Department of Neurology, University of Münster, Germany
,
P. Kraft
4   Department of Neurology, University Hospital of Würzburg, Germany
,
S. G. Meuth
3   Department of Neurology, University of Münster, Germany
5   Institute of Physiology I – Neuropathophysiology, University of Münster, Germany
,
C. Kleinschnitz
4   Department of Neurology, University Hospital of Würzburg, Germany
,
H. F. Langer
1   University Clinic for Cardiovascular Medicine, University of Tuebingen, Germany
2   Section for Cardioimmunology, University of Tuebingen, Germany
› Author AffiliationsThis work was supported by the Volkswagen Foundation (Lichtenberg program), German Heart Foundation and Wilhelm Sander Foundation, the Juniorprofessorenprogramm of Baden-Wuerttemberg, the Tuebingen platelet investigative consortium (TuePIC) funded by the German Research Council (Deutsche Forschungsgemeinschaft (DFG), KFO 274 – Platelets – basic mechanisms and clinical implications) and the excellence cluster ‘Cells in Motion’ (CiM), and the DFG Sonderforschungsbereich 688 (SFB 688).
Further Information

Publication History

received: 19 November 2014

accepted in revised form: 04 May 2015

Publication Date:
28 December 2017 (online)

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Summary

There is emerging evidence that platelets have an important role in inflammation beyond their involvement in hemostasis. Platelets can contribute to inflammatory reactions via crosstalk both with immune cells and endothelial cells. Inflamed vessels are characterized by the presence of activated endothelial cells. These activated endothelial cells upregulate receptors necessary for leukocyte recruitment, but also for the adhesion of platelets. Subsequently, immune cells can bind to platelets through adhesion receptors presented on the platelet surface, thus supporting leukocyte recruitment to the vessel wall. There are several neurological diseases associated with vascular inflammation including multiple sclerosis (MS) and stroke. Increased markers of platelet activation could be demonstrated in patients suffering from MS compared to healthy individuals. Reports from murine models indicate that platelets may be of importance for disease progression and severity by mediating leukocyte recruitment as one potential underlying mechanism. Blocking platelet function disease severity was considerably ameliorated. Moreover, processes of tissue remodelling may be influenced by platelet derived mediators. Whether a role of platelets for vascular inflammation can be extrapolated to further neurological diseases will have to be investigated in further in depth experimental and clinical trials.

Conclusion

Platelets and platelet associated mechanisms may offer novel starting points to understand neurovascular diseases from a different point of view and to develop novel approaches to access the disease.

Zusammenfassung

Neben ihrer Rolle in der Hämostase sind Thrombozyten auch an Entzündungsvorgängen beteiligt. Thrombozyten können sowohl durch Interaktionen mit Immunzellen als auch mit Endothelzellen zu Entzündungsreaktionen beitragen. Vaskuläre Inflammation ist gekennzeichnet durch aktiviertes Endothel. Diese aktivierten Endothelzellen sorgen dafür, dass Rezeptoren hochreguliert werden, die für die Rekrutierung von Leukozyten, aber auch für die Adhäsion von Thrombozyten notwendig sind. In der Folge können Immunzellen mittels Adhäsionsrezeptoren, die auf der Oberfläche der Thrombozyten präsentiert werden, an Thrombozyten binden, wodurch die Rekrutierung von Leukozyten an die Gefäßwand vermittelt wird. Im zentralen Nervensystem gibt es mehrere Erkrankungen wie die Multiple Sklerose (MS) oder der Schlaganfall, die mit vaskulärer Inflammation assoziiert sind. Bei Patienten mit MS konnten erhöhte Marker für Plättchenaktivierung im Vergleich zu Gesunden nachgewiesen werden. Erkenntnisse aus Mausmodellen deuten zudem darauf hin, dass Thrombozyten bedeutsam für die Krankheitsprogression und Krankheitsausprägung sein können, zum Beispiel durch die Vermittlung von Leukozytenrekrutierung in die inflammatorische Läsion. Unter einer Blockade der Thrombozytenfunktion war eine deutliche Verbesserung der Schwere der Erkrankung sichtbar. Darüber hinaus könnten Prozesse des Gewebe-Remodellings durch Mediatoren aus Thrombozyten beeinflusst werden. Ob eine Beteiligung von Thrombozyten an vaskulärer Inflammation auf weitere neurologische Erkrankungen ausgeweitet werden kann, muss in zukünftigen experimentellen und klinischen Arbeiten untersucht werden.

Schlussfolgerung

Thrombozyten bzw. Thrombozyten-assoziierte Mechanismen könnten neue Ausgangspunkte darstellen, um neurovaskuläre Erkrankungen aus einem anderen Blickwinkel zu verstehen oder neue pathophysiologische und therapeutische Ansätze zu definieren.

Keywords

Platelets - inflammation

Schlüsselwörter

Thrombozyten - Entzündung
 

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