Microparticles: markers and mediators of sepsis-induced microvascular dysfunction, immunosuppression, and AKI

Abstract

Sepsis is a severe and complex syndrome that lacks effective prevention or therapeutics. The effects of sepsis on the microvasculature have become an attractive area for possible new targets and therapeutics. Microparticles (MPs) are cell membrane-derived particles that can promote coagulation, inflammation, and angiogenesis, and they can participate in cell-to-cell communication. MPs retain cell membrane and cytoplasmic constituents of their parental cells, including two procoagulants: phosphatidylserine and tissue factor. We highlight the role of microparticles released by endothelial and circulating cells after sepsis-induced microvascular injury, and we discuss possible mechanisms by which microparticles can contribute to endothelial dysfunction, immunosuppression, and multiorgan dysfunction--including sepsis-AKI. Once viewed as cellular byproducts, microparticles are emerging as a new class of markers and mediators in the pathogenesis of sepsis.

Figure 1

Schematic view of sepsis-induced microparticles (MPs) released into the systemic circulation following microvascular injury. MPs may arise from different cell types and are between 0.2 and 2 μm in size. MPs can contribute to inflammation, DIC initiation, and immunosuppression, which contribute to multiple organ injury including acute kidney injury (AKI), and can cause further microvascular injury and MPs release.

Figure 2

Schematic representation of functions attributable to microparticles (MPs) during sepsis. During microvascular injury, endothelial cells and circulating cells such as immune cells and platelets release MPs. MPs then exert several pro-thrombotic, pro-inflammatory, and immunosuppressive actions on these same cells, perpetuating harmful cycles and microvascular injury. During sepsis, the majority of circulating MPs are derived from platelets.

Figure 3

3a During normal/ healthy states, microparticles (MPs) are released from circulating cells in small numbers; 3b during sepsis, endothelial and microvascular injury occur with subsequent release of MPs, which perpetuates the microvascular injury and promotes inflammation, immunosuppression, and DIC; 3c during CKD, there is endothelial damage and increased number of circulating MPs. The role of these MPs during CKD is yet to be established; 3d represents a hypothetical association between sepsis events (3b) in patients with pre-existing chronic disease such as CKD (3c). It is known that CKD amplifies sepsis (79). It is possible that MPs may participate in this event.