Microvesicles (MVs) are small spherical fragments of plasma membrane between 50 and 1000 nm in diameter. MVs arise through direct outward budding and fission of the plasma membrane. As almost all cells, human red blood cells (RBCs) are able to release MVs into extracellular environment under stimulating or storage conditions. Recently, it has been known that MVs not only play a role in homeostasis but also have diverse functions in cell-cell interactions and in the pathogenesis of diseases. In this chapter, the formation and release of MVs from human RBCs have been described. In addition, MVs have demonstrated to be potential vehicle for transport of nucleic acid and other molecules to the target cells. Although RBC-derived MVs are potential material for the development of delivery systems, it is still a great challenge to the clinical application. Future research should pay more attention to MVs as biological targets for diagnosis and practical therapeutics of cancer and other diseases.
The chapter describes the likely molecular mechanisms leading to the aggregation of human red blood cells (RBCs) under conditions of physiological coagulation when prostaglandin E2 (PGE2) or lysophosphatidic acid (LPA) is released from activated platelets and under pathophysiological conditions, in particular thrombi formation in sickle cell disease when patients are in a vaso-occlusive crisis. In both scenarios cation channels are activated. This leads to an increase of the free intracellular Ca2+ concentration resulting in an activation of the lipid scramblase, which in turn mediates a movement of phosphatidylserine (PS) from the inner to the outer membrane leaflet. In addition, the increased Ca2+ concentration leads to the activation of the Gardos channel. Experiments suggesting this mechanism have been performed with fluorescence microscopy, flow cytometry as well as single-cell force spectroscopy. The Ca2+-triggered RBC aggregation force has been identified to be close to 100 pN, a value large enough to play a significant role during thrombus formation or in pathological situations.
Part of the book: Erythrocyte