Relevance of Measuring Circulating Microparticles During Organ and Stem-Cell Transplantation

Abstract

M icroparticles (MP) were first described by Wolf (1) as "cell dust in human plasma" in 1967. This "dust" is derived from circulating cells and endothelial cells after cell activation or apoptosis and contains vesicles with a diameter between 0.1 and 1.0 m. During MP formation, the asymmetric order of cell membrane collapses, and negative phospholipids such as phosphatidylserine reach the MP surface were they can usually be detected by annexin V. Mechanism of MP release is shown in Figure 1. Furthermore, MP are composed of lipids and proteins transferred from their "parent cells." This helps to determine the origin of MP: endothelial-derived MP for example carry tissue factor on their surface and are positive for CD31 and CD144. In healthy humans, most MP in plasma are CD61 positive and were believed to be platelet derived; but in recent years, there is more and more evidence that they are mainly released from megakaryocytes directly into circulation together with platelets. These MP are important initiators for plasmatic coagulation by presenting a negatively charged phospholipid surface with binding sites for several different coagulation factors (2). In patients suffering from Scott's syndrome, there is an impairment of MP formation resulting in a bleeding disorder with hematoma and bleeding complications. On the other side, increased numbers of MP derived from platelets and megakaryocytes are associated with a hypercoagulant status like in patients with venous thrombosis (3). In addition to their rule in hemostasis, MP are involved in intercellular transport and transfer of bioactive molecules, cell activation, and inflammation: endothelial cell-derived MP activate granulocytes, induce expression of tissue factor in monocytes, and influence angiogenesis through metalloproteinase. In turn, MP from leukocytes stimulate the endothelium. So it is not surprising that in various disorders such as diabetes, hypertension, or malignancies, enhanced plasma levels of different MP can be found reflecting the apoptotic and activation status of the parent's cell population.From a clinical point of view, the question is how can we use the information given from individual MP pattern can be used for patient's diagnosis or prognosis? Especially for organ and hematopoetic stem-cell transplantation measuring MP in plasma provides the opportunity to get information about activation status of different cell types. In this context, it seems helpful to determine MP levels at different points of time during transplantation period to be able to interpret increased or decreased values at certain points of time. MP levels in patients before transplantation regularly differ from healthy humans as these patients mostly suffer from severe disorders. For example, patients with end-stage renal failure show increased MP levels during the time of hemodialysis normalized MP levels after uncomplicated renal transplantation (4). Similar developments were found in patients with hepatitis C undergoing liver transplantation. MP levels usually norma...