Mechanisms of Cellular Activation by Platelet Microparticles

Abstract

Introduction: Eukaryotic cells, after activation, shed components of their plasma membranes into the extracellular space.1,2 Such fragments may include cytoplasmic elements and are known colloquially as microparticles (MPs). Monocytes,3 lymphocytes,4 endothelial cells,5 erythrocytes,6 and granulocytes7 have been shown to vesiculate either in vitro or in vivo. MPs from other sources have also been reported to exist in vivo.8,9 In addition, platelets have been found to vesiculate following activation by agonists.10,11 Platelets activated with collagen and/or thrombin, by the Ca2+ ionophore A23187 or the complement protein C5b-9, induce platelet microparticle (PMP) formation. While the effect of these agonists is to increase platelet cytosolic Ca2+ concentration, it has been suggested that calpain activation,12-14 cytoskeletal reorganization,12,14,15 protein phosphorylation14 and phospholipid translocation16,17 also may have roles in PMP formation. Shear stress has been shown to induce platelet vesiculation. The mechanisms involved include the binding of von Willebrand factor (vWF) to either glycoprotein (GP)-Ib or GP IIb/IIIa.18 These in vitro observations are supported by an ex vivo model of high arterial shear stress. High shear stress, as pertains in the atherosclerotic vasculature, was shown to activate platelets and trigger PMP formation. Meanwhile, under physiological or simulated shear stress conditions in arteries with a minor degree of stenosis, no vesiculation occurred.19