New methodological strategies in haematology using cell-derived microvesicles

www.nietoeditores.com.mx Microvesicles as messengers of cell and tissue dysfunction Cellular microvesicles are membrane nanometric vesicles, 0.1-1 μm in size, released into body fluids by activated cells or during apoptosis in a variety of pathological conditions [1-4]. Characteristically, cell activation disturbs phospholipids transport and cytoskeleton membrane connexions resulting in phosphatidylserine exposure, membrane blebbing and vesiculation (Fig. 1). The most well known cellular MVs are those of platelet, leukocyte, erythrocyte and endothelial cell origin found in circulating blood [5]. A number of studies have demonstrated that stimulation of these cells is followed by the characteristic features of cell activation: increased levels of cytoplasmic calcium associated to translocation of phosphatidylserine from the inner to the outer leaflet of the membrane and activation of calpains that, by cleaving cytoskeletal filaments, facilitate MVs shedding [6]. The increase in intracellular Ca2+ concentration induces a disordered state in the phospholipids asymmetry of quiescent cells that is normally maintained by the concerted activity of transporter proteins [7, 8]: the ATP-dependent inwardand outward-directed transporters, flippases (aminophospholipid translocase) and floppases (including the ATP-binding cassette transporter ABCA1) respectively, and the Ca2+-dependent scramblases that facilitate bidirectional movement between the 2 membrane leaflets. The rate of phosphatidylserine translocation has been found to be sensitive to the altered expression of ABCA1 [9].