title: 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.
authors.affiliation: Unit of Autoimmunity and Vascular Inflammation, Division of Regenerative Medicine, Gene Therapy and Stem Cells, Istituto Scientiﬁco San Raffaele and Universita Vita-Salute San Raffaele, Milan, Italy. maugeri.norma@hsr.it
authors.forename: Norma
authors.initials: N
authors.lastname: Maugeri
authors.forename: Simona
authors.initials: S
authors.lastname: Malato
authors.forename: Eti A
authors.initials: EA
authors.lastname: Femia
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Pugliano
authors.forename: Lara
authors.initials: L
authors.lastname: Campana
authors.forename: Francesca
authors.initials: F
authors.lastname: Lunghi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Rovere-Querini
authors.forename: Federico
authors.initials: F
authors.lastname: Lussana
authors.forename: Gianmarco
authors.initials: G
authors.lastname: Podda
authors.forename: Marco
authors.initials: M
authors.lastname: Cattaneo
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciceri
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Manfredi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D019007:P-Selectin / Q000276:immunology / Q000378:metabolism*; D010587:Phagocytosis / Q000235:genetics* / Q000276:immunology; D015539:Platelet Activation / Q000187:drug effects / Q000276:immunology; D010976:Platelet Count; D011087:Polycythemia Vera / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D006918:Hydroxyurea