Shedding of procoagulant microparticles from unstimulated platelets by integrin-mediated destabilization of actin cytoskeleton.
Platelet activation by potent, Ca(2+)-mobilizing agonists results in shedding of microparticles that are active in coagulation. Here we show that platelets under storage produce procoagulant microparticles in the absence of agonist. Microparticle formation by resting platelets results from alphaIIbbeta3 signaling to destabilization of the actin cytoskeleton in the absence of calpain activation. Integrin-mediated spreading of platelets over fibrinogen similarly results in microparticle formation. After transfusion of stored platelet preparations to thrombocytopenic patients, the microparticles contribute to coagulant activity in vivo.
Cauwenberghs
Sandra
S
Department of Biochemistry, CARIM, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
Feijge
Marion A H
MA
Harper
Alan G S
AG
Sage
Stewart O
SO
Curvers
Joyce
J
Heemskerk
Johan W M
JW
D008841:Actin Cytoskeleton / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects; D016913:Blood Component Transfusion / Q000009:adverse effects; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002154:Calpain / Q000378:metabolism; D003029:Coagulants / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism; D011309:Preservation, Biological; D015398:Signal Transduction; D013921:Thrombocytopenia / Q000378:metabolism / Q000628:therapy
D002121:Calcium Channel Blockers; D003029:Coagulants; D039661:Integrin beta3; D040201:Platelet Membrane Glycoprotein IIb; D002154:Calpain