Polyphosphate nanoparticles on the platelet surface trigger contact system activation
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Polyphosphate nanoparticles on the platelet surface trigger contact system activation. / Verhoef, Johan J F; Barendrecht, Arjan D; Nickel, Katrin F; Dijkxhoorn, Kim; Kenne, Ellinor; Labberton, Linda; McCarty, Owen J T; Schiffelers, Raymond; Heijnen, Harry F; Hendrickx, Antoni P; Schellekens, Huub; Fens, Marcel H; de Maat, Steven; Renné, Thomas; Maas, Coen.
In: BLOOD, Vol. 129, No. 12, 23.03.2017, p. 1707-1717.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Polyphosphate nanoparticles on the platelet surface trigger contact system activation
AU - Verhoef, Johan J F
AU - Barendrecht, Arjan D
AU - Nickel, Katrin F
AU - Dijkxhoorn, Kim
AU - Kenne, Ellinor
AU - Labberton, Linda
AU - McCarty, Owen J T
AU - Schiffelers, Raymond
AU - Heijnen, Harry F
AU - Hendrickx, Antoni P
AU - Schellekens, Huub
AU - Fens, Marcel H
AU - de Maat, Steven
AU - Renné, Thomas
AU - Maas, Coen
N1 - Copyright © 2017 American Society of Hematology.
PY - 2017/3/23
Y1 - 2017/3/23
N2 - Polyphosphate is an inorganic polymer that can potentiate several interactions in the blood coagulation system. Blood platelets contain polyphosphate, and the secretion of platelet-derived polyphosphate has been associated with increased thrombus formation and activation of coagulation factor XII. However, the small polymer size of secreted platelet polyphosphate limits its capacity to activate factor XII in vitro. Thus, the mechanism by which platelet polyphosphate contributes to thrombus formation remains unclear. Using live-cell imaging, confocal- and electron microscopy, we show that activated platelets expose polyphosphate on their cell surface. The apparent polymer size of membrane-associated polyphosphate largely exceeds that of secreted polyphosphate. Ultracentrifugation fractionation experiments revealed that membrane-associated platelet polyphosphate is condensed into insoluble spherical nanoparticles with divalent metal ions. In contrast to soluble polyphosphate, membrane-associated polyphosphate nanoparticles potently activate factor XII. Our findings identify the presence of membrane-associated polyphosphate in a nanoparticle state on the surface of activated platelets. We propose that these polyphosphate nanoparticles mechanistically link the procoagulant activity of platelets with the activation of coagulation factor XII.
AB - Polyphosphate is an inorganic polymer that can potentiate several interactions in the blood coagulation system. Blood platelets contain polyphosphate, and the secretion of platelet-derived polyphosphate has been associated with increased thrombus formation and activation of coagulation factor XII. However, the small polymer size of secreted platelet polyphosphate limits its capacity to activate factor XII in vitro. Thus, the mechanism by which platelet polyphosphate contributes to thrombus formation remains unclear. Using live-cell imaging, confocal- and electron microscopy, we show that activated platelets expose polyphosphate on their cell surface. The apparent polymer size of membrane-associated polyphosphate largely exceeds that of secreted polyphosphate. Ultracentrifugation fractionation experiments revealed that membrane-associated platelet polyphosphate is condensed into insoluble spherical nanoparticles with divalent metal ions. In contrast to soluble polyphosphate, membrane-associated polyphosphate nanoparticles potently activate factor XII. Our findings identify the presence of membrane-associated polyphosphate in a nanoparticle state on the surface of activated platelets. We propose that these polyphosphate nanoparticles mechanistically link the procoagulant activity of platelets with the activation of coagulation factor XII.
U2 - 10.1182/blood-2016-08-734988
DO - 10.1182/blood-2016-08-734988
M3 - SCORING: Journal article
C2 - 28049643
VL - 129
SP - 1707
EP - 1717
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 12
ER -
