The mechanisms of MP formation are complex and not completely elucidated. Following cell activation or apop- tosis, MPs formation is dependent on a sustained rise in the cytosolic Ca 2+ concentration with the consequent activation of different cytosolic enzyme relevant to MPs formation. Calpain is one of the most important enzyme and has several actions in MPs generation including cleaving of cytoskeletal filaments, facilitating microparticle shedding, and activating apoptosis through procaspase-3 [38] . These changes result in cytoskeletal reorganization, loss of the asymmetric distribution of aminophospholipid, membrane blebbing and MP formation [39] . Some release of shedding vesicles takes place from resting cells, however the rate of the process increases dramatically upon stimulation [40] . Ca 2+ is not the only second messenger involved. In various cell types, in fact, phorbol ester activation of protein kinase C (PKC) is also effective. In PC12 cells, shedding vesicles are released upon application of phorbol esters and not of Ca 2+ ionophores. The purinergic receptors of ATP, a ligand released by many cell types, have an important role. In dendritic cells, macrophages and microglia, activation of the purinergic receptor channel, P2X7, was found to induce intense release of MPs. In other cell types (such as PC12 and platelets), activation of the P2Y receptors coupled with the Gq protein was found to be effective.