Clearance of circulating activated platelets in polycythemia vera and essential thrombocythemia.
Blood
; 118(12): 3359-66, 2011 Sep 22.
Article
em En
| MEDLINE
| ID: mdl-21705500
ABSTRACT
Essential thrombocythemia (ET) and polycythemia vera (PV) are characterized by persistent platelet activation. The mechanisms involved in their clearance are poorly characterized. In the present study, we report that leukocytes were actively involved in platelet disposal in 51 patients with ET and 30 with PV, but not in 70 age- and sex-matched controls. The fraction of circulating neutrophils and monocytes that had phagocytosed platelets, as assessed by flow cytometry, was significantly higher in patients with PV or ET, independently of hydroxyurea treatment, than in controls. Platelet phagocytosis by circulating leukocytes was confirmed by confocal and electron microscopy. The lack of effect of hydroxyurea, which disrupts the P-selectin/P-selectin glycoprotein ligand 1 (PSGL-1) interaction, suggests a P-selectin-independent mechanism. This hypothesis was confirmed in an ad hoc animal model based on the in vivo injection of activated platelets from P-selectin(+/+) and P-selectin(-/-) mice. P-selectin expression was associated with an earlier and effective clearance of platelets by neutrophils. A second delayed, P-selectin-independent phase actively involved monocytes. Our results suggest that phagocytic clearance of platelets by leukocytes occurs in PV and ET, possibly involving P-selectin-dependent and -independent pathways, thus representing a novel mechanism to remove activated platelets from the circulation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fagocitose
/
Policitemia Vera
/
Plaquetas
/
Glicoproteínas de Membrana
/
Monócitos
/
Transdução de Sinais
/
Selectina-P
/
Trombocitemia Essencial
/
Neutrófilos
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Aged80
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article