Endothelial microparticles activate endothelial cells to facilitate the inflammatory response

Abstract

Abstract. Endothelial microparticles (EMPs) and endothelial cells (ECs) are involved in the pathophysiological mechanisms of sepsis and septic shock. EMPs are small vesicles released by ECs and are considered biomarkers for endothelial cell function and mediators for intercellular information exchange. However, the effect of EMPs on their parental ECs remains unknown. The present study collected tumor necrosis factor-α-derived EMPs and detected the proinflammatory cytokines released from unstimulated and EMP-stimulated ECs by proteome profiler array. This revealed that EMPs induce an inflammatory response in ECs. Within this response, interferon γ-induced protein 10 was revealed by ELISA to be associated with the activity of EMPs in a time-and dose-dependent manner. It was hypothesized that the possible mechanism underlying this phenomenon was nuclear factor-κB. This was demonstrated to be crucial for the expression of IP-10 in EMP-stimulated ECs and the function of EMPs by immunofluorescence and western blot analysis. The present study enhances understanding of the involvement of EMPs and ECs in sepsis and will assist with the early diagnosis and treatment of sepsis.

Large Extracellular Vesicles: Have We Found the Holy Grail of Inflammation?

“…As emphasized at the beginning of this paragraph, interactions between EMVs and endothelial cells are examples of an inflammation cycle. In the same context, Liu et al (152) have recently confirmed that the axis of TNF-endothelium-EMV-endothelium is a self-perpetuating inflammatory process. They concluded that TNF-induced EMVs stimulate endothelial cells to produce proinflammatory cytokines including interferon gamma-induced protein 10 (IP-10) (152).…”

“…In the same context, Liu et al (152) have recently confirmed that the axis of TNF-endothelium-EMV-endothelium is a self-perpetuating inflammatory process. They concluded that TNF-induced EMVs stimulate endothelial cells to produce proinflammatory cytokines including interferon gamma-induced protein 10 (IP-10) (152). Interestingly, EMVs can also be generated in the process of endothelial cell stimulation by bubbles, which represents a laboratory model of decompression sickness (DCS) (153).…”

Docked severe acute respiratory syndrome coronavirus 2 proteins within the cutaneous and subcutaneous microvasculature and their role in the pathogenesis of severe coronavirus disease 2019

“…Both of these mechanisms may be shared by the original SARS-CoV virus[ [16] , [17] , [18] , [19] ]. Jettisoned viral capsid microparticles that include the spike glycoprotein in the circulation can be endocytosed by ACE2+ endothelia that could result in complement activation via MBL activation without implying viral replication [ [20] , [21] , [22] ]. Second, there may be viremia inducing systemic MASP2-driven thrombosis and complement deposition by cleaving C4 and C2 [ 20 , 23 ], as suggested by the detection of coronavirus RNA in the plasma during SARS-CoV [ 24 , 25 ].…”

The Ability of Extracellular Vesicles to Induce a Pro-Inflammatory Host Response

“…The interaction between EVs and the endothelium may be amplified by the release of pro-inflammatory cytokines [42] and platelet activating factor [23] from endothelial cells. In turn, endothelial-derived EVs further activate the endothelium, thus further perpetuating the inflammatory response [29]. Taken together, EVs seem to mediate increased adherence of immune cells to the endothelium with the induction of a pro-inflammatory response.…”