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Thromb Haemost ; 117(9): 1772-1781, 2017 08 30.
Artículo en Inglés | MEDLINE | ID: mdl-28837205

RESUMEN

Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) is an immunoreceptor initially known to be expressed on neutrophils and monocytes/macrophages. TREM-1 acts as an amplifier of the inflammatory response during both infectious and aseptic inflammatory diseases. Another member of the TREM family, The Triggering receptor expressed on myeloid cells Like Transcript-1 (TLT-1) is exclusively expressed in platelets and promotes platelet aggregation. As the gene that encodes for TLT-1 is located in the TREM-1 gene cluster, this prompted us to investigate the expression of TREM-1 on platelets. Here we show that TREM-1 is constitutively expressed in α-granules and mobilised at the membrane upon platelet activation. Pharmacologic inhibition of TREM-1 reduces platelet activation as well as platelet aggregation induced by collagen, ADP, and thrombin in human platelets. Aggregation is similarly impaired in platelets from Trem-1-/- mice. In vivo, TREM-1 inhibition decreases thrombus formation in a carotid artery model of thrombosis and protects mice during pulmonary embolism without excessive bleeding. These findings suggest that TREM-1 inhibition could be useful adducts in antiplatelet therapies.


Asunto(s)
Plaquetas/metabolismo , Agregación Plaquetaria , Embolia Pulmonar/sangre , Trombosis/sangre , Receptor Activador Expresado en Células Mieloides 1/sangre , Animales , Plaquetas/efectos de los fármacos , Modelos Animales de Enfermedad , Genotipo , Humanos , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Péptidos/farmacología , Fenotipo , Adhesividad Plaquetaria , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Embolia Pulmonar/genética , Embolia Pulmonar/prevención & control , Vesículas Secretoras/metabolismo , Trombosis/genética , Trombosis/prevención & control , Receptor Activador Expresado en Células Mieloides 1/antagonistas & inhibidores , Receptor Activador Expresado en Células Mieloides 1/deficiencia , Receptor Activador Expresado en Células Mieloides 1/genética
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