Microparticles as biological vectors of activated protein C treatment in sepsis

Activated protein C (APC), a physiological coagulation inhibitor, has been shown to reduce mortality in patients with severe sepsis. APC exerts pleiotropic cytoprotection by a mechanism that requires its interaction with endothelial cell protein C receptor and protease-activated receptor-1 on target cells. In the previous issue, Pérez-Casal and colleagues elegantly demonstrate that APC, using its recombinant form (rhAPC), can communicate to target cells through release of microparticles (MPs), small membrane vesicles released from activated cells, to induce anti-apoptotic and anti-inflammatory properties that might participate in the improvement of patient outcome. Of interest is the fact that APC itself promotes the release of MPs from target cells including endothelial cells and monocytes. These MPs bear the endothelial cell protein C receptor/APC molecules and can transfer the message to target cells including those of origin to induce cytoprotection. The long-range APC signal can thus be mediated by MPs in vivo upon pharmacological treatment using rhAPC in severe septic patients. A novel pharmacological approach targeting MP production and properties could therefore be used to treat severe sepsis in addition to other well-known actions of APC via direct interaction with the cells of interest.