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Clearance of circulating activated platelets in polycythemia vera and essential thrombocythemia.

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.

journal_name

Blood

journal_title

Blood

authors

Maugeri N,Malato S,Femia EA,Pugliano M,Campana L,Lunghi F,Rovere-Querini P,Lussana F,Podda G,Cattaneo M,Ciceri F,Manfredi AA

doi

10.1182/blood-2011-02-337337

subject

Has Abstract

pub_date

2011-09-22 00:00:00

pages

3359-66

issue

12

eissn

0006-4971

issn

1528-0020

pii

blood-2011-02-337337

journal_volume

118

pub_type

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