The Commensal Microbiota Enhances ADP-Triggered Integrin αIIbß3 Activation and von Willebrand Factor-Mediated Platelet Deposition to Type I Collagen.
Int J Mol Sci
; 21(19)2020 Sep 28.
Article
en En
| MEDLINE
| ID: mdl-32998468
The commensal microbiota is a recognized enhancer of arterial thrombus growth. While several studies have demonstrated the prothrombotic role of the gut microbiota, the molecular mechanisms promoting arterial thrombus growth are still under debate. Here, we demonstrate that germ-free (GF) mice, which from birth lack colonization with a gut microbiota, show diminished static deposition of washed platelets to type I collagen compared with their conventionally raised (CONV-R) counterparts. Flow cytometry experiments revealed that platelets from GF mice show diminished activation of the integrin αIIbß3 (glycoprotein IIbIIIa) when activated by the platelet agonist adenosine diphosphate (ADP). Furthermore, washed platelets from Toll-like receptor-2 (Tlr2)-deficient mice likewise showed impaired static deposition to the subendothelial matrix component type I collagen compared with wild-type (WT) controls, a process that was unaffected by GPIbα-blockade but influenced by von Willebrand factor (VWF) plasma levels. Collectively, our results indicate that microbiota-triggered steady-state activation of innate immune pathways via TLR2 enhances platelet deposition to subendothelial matrix molecules. Our results link host colonization status with the ADP-triggered activation of integrin αIIbß3, a pathway promoting platelet deposition to the growing thrombus.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trombosis
/
Plaquetas
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Factor de von Willebrand
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Adenosina Difosfato
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Complejo GPIIb-IIIa de Glicoproteína Plaquetaria
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Colágeno Tipo I
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Int J Mol Sci
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Suiza