Bench-to-bedside review: Circulating microparticles - a new player in sepsis?

Abstract

In sepsis, inflammation and thrombosis are both the cause and the result of interactions between circulating (for example, leukocytes and platelets), endothelial and smooth muscle cells. Microparticles are proinflammatory and procoagulant fragments originating from plasma membrane generated after cellular activation and released in body fluids. In the vessel, they constitute a pool of bioactive effectors pulled from diverse cellular origins and may act as intercellular messengers. Microparticles expose phosphatidylserine, a procoagulant phospholipid made accessible after membrane remodelling, and tissue factor, the initiator of blood coagulation at the endothelial and leukocyte surface. They constitute a secretion pathway for IL-1β and up-regulate the proinflammatory response of target cells. Microparticles circulate at low levels in healthy individuals, but undergo phenotypic and quantitative changes that could play a pathophysiological role in inflammatory diseases. Microparticles may participate in the pathogenesis of sepsis through multiple ways. They are able to regulate vascular tone and are potent vascular proinflammatory and procoagulant mediators. Microparticles' abilities are of increasing interest in deciphering the mechanisms underlying the multiple organ dysfunction of septic shock.

Leukocyte-Derived Microparticles in Vascular Homeostasis

“…44 Monocyte-derived MPs (MonoMPs) purified from monocyte suspension display coexisting tissue factor (TF), and activated protein C (APC) and thrombomodulin anticoagulant activity at their surface 45 ( Figure 2). MonoMPs also express the endothelial cell protein C receptor (EPCR), thereby promoting the activation of anticoagulant protein C by the thrombin-thrombomodulin complex 46,47 (Figure 2). After exposure to endotoxin, there is an early increase in MonoMPs associating TF procoagulant activity.…”

Synergistic Effect of Thrombin and CD40 Ligand on Endothelial Matrix Metalloproteinase-10 Expression and Microparticle Generation In Vitro and In Vivo

“…19 We assessed the levels of MPs in our experimental model ( Figure III in the online-only Data Supplement). As shown in Figure 5A, the amount of MPs isolated from platelet-poor plasma of LPSinjected mice was higher in WT and Mmp10 -/-animals compared with saline.…”

Microparticles and Exosomes: Are They Part of Important Pathways in Sepsis Pathophysiology?

“…Taken together, these differences indicate that shedding seems to be a well-regulated process that originates unique microparticle characteristics depending on the cell source, stimulus, scenario and pathophysiological conditions. More recent data demonstrate that, besides proteins and lipid composition on the surface of microparticles, the inner portion of these vesicles also contain several enzymes and genetic material capable of interacting and producing effects on the target cell (Meziani et al, 2010). Subunits of enzymes with superoxide producing activity like NADPH oxidase have been identified on microparticles originated from platelets (Janiszewski et al, 2004).…”