Stimulation of blood mononuclear cells with bacterial virulence factors leads to the release of pro-coagulant and pro-inflammatory microparticles

Abstract

Severe infectious diseases remain a major and life-threatening health problem. In serious cases a systemic activation of the coagulation cascade and hypovolemic shock are critical complications that are associated with high mortality rates. Here we report that blood mononuclear cells, stimulated with M1 protein of Streptococcus pyogenes or other bacterial virulence factors, produce not only pro-coagulant, but also pro-inflammatory microparticles (MPs). Our results also show that activation of the contact system on MPs contributes to these two effects. Phosphatidylserine (PS) plays an important role in these processes as its upregulation on MPs allows an assembly and activation of the contact system. This in turn results in stabilization of the tissue factor-induced clot and a processing of high-molecular-weight kininogen by plasma kallikrein followed by the release of bradykinin, a potent vascular mediator. Pro-coagulant monocyte-derived MPs were identified in plasma samples from septic patients and further analysis of MPs from these patients revealed that their pro-coagulant activity is dependent on the tissue factor- and contact system-driven pathway.