New locations of intravascular tissue factor

Summary

Tissue factor (TF) is the major initiator of blood coagulation, and a mediator of inflammation, angiogenesis, and carcinogenesis. According to recent evidence, preformed TF and inducible expression of the protein is observed in several blood components. TF is apparently constitutively expressed on circulating microparticles, and can be exposed within minutes on the cell membrane of activated eosinophils and platelets, and, potentially, on neutrophils. Expression in monocytes and neutrophils largely requires transcriptional activation of the TF gene. Eosinophils appear to harbour the highest concentration of preformed TF among all blood components under resting conditions. TF expression in eosinophil progenitor cells is substantially higher than in precursors of other granulocyte fractions. Eosinophil TF promotes transendothelial migration, which documents that presynthesized TF in blood supports functions apart from coagulation. It is still an open question how the intravascular TF is activated to trigger initiation of coagulation. TF activation in different blood components is likely to be differentially regulated according to the (patho)physiologic context.

Zusammenfassung

TF (tissue factor), ist das Starterprotein der Blutgerinnung. Außerdem ist TF bei Entzündungsprozessen, in der Gefäßbildung und bei der Entstehung von Tumoren von zentraler Bedeutung. Vor kurzem konnte TF in verschiedenen Blutbestandteilen nachgewiesen werden. TF wird auf zirkulierenden Mikropartikeln anscheinend konstitutiv exprimiert und kann innerhalb von Minuten auf der Zellmembran aktivierter Eosinophiler und Plättchen erscheinen. TF wird möglicherweise auch von Neutrophilen exprimiert. Die TFExpression in Monozyten und Neutrophilen erfordert im wesentlichen die Transkription des TF-Gens. Eosinophile beinhalten scheinbar die höchste Konzentration an bereits gebildetem TF unter allen nicht aktivierten Blutbestandteilen. Die TF-Expression in eosinophilen Vorläuferzellen ist beträchtlich höher als in Vorläuferzellen anderer Granulozytenfraktionen. TF auf Eosinophilen fördert die transendotheliale Migration. Dies belegt, dass vorgebildeter TF im Blut noch weitere Funktionen außer der Gerinnung unterstützt. Auf welche Weise der intravasale TF aktiviert wird, um den Gerinnungsstart auszulösen, ist unklar. Die Aktivierung von TF in verschiedenen Blutbestandteilen wird höchstwahrscheinlich differenziell, entsprechend dem jeweiligen (patho)physiologischen Kontext, reguliert.

Keywords

Tissue factor - coagulation - encryption - activation - platelets - monocytes - eosinophils - neutrophils - microparticles - intravascular - blood-borne - inflammation

Schlüsselwörter

Tissue-Faktor - Gewebethromboplastin - Blutgerinnung - Enkryptierung - Aktivierung - Plättchen - Monozyten - Eosinophile - Neutrophile - Mikropartikel - intravasal - Entzündung

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