Article
Ectonucleotidase-bearing plasma microparticles as possible biomarkers with therapeutical implications in liver diseases
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Published: | December 12, 2014 |
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Activation of cells due to physical or chemical stress and the response to pro-inflammatory cytokines, e.g. TNF‑α and IL-1β,leads to membrane destabilization with distinct modifications of the plasma membrane. Inflammation and apoptosis lead to an externalization of phosphatidylserine and bleb formation, resulting in the release of submicron fragments, so called microparticles (MP).
MP can be isolated by ultracentrifugation and detected by flow cytometry, as they are characterized not only by cell-specific cytosol, but further by distinct surface antigens. CD39 is incorporated in plasma MP and has been shown to phosphohydrolyze extracellular proinflammatory adenosine triphosphate (ATP). Plasma MP exhibit CD39-dependent paracrine effects and were demonstrated to modulate endothelial inflammation.
CD39 is involved in the modulation of numerous acute and chronic liver diseases and CD39+ MP are differentially noted in mice and patients with liver injury. Ectonucleotidase bearing immune and stem cell MP were tested as potential biomarkers in pharmacological acute liver failure, acute rejection after liver transplantation, in xeno-liver transplantation and in obese patients with fatty liver disease. Mechanistic studies in vitro indicate that MP might further represent important regulators of intercellular communication.
CD39+ MP subpopulations are suggested to have future potential to distinguish between mild and severe acute and chronic liver injury, respectively, and define patients at high risk for acute rejection after organ transplantation. Further research is needed to determine which MP subsets represent robust biomarkers of clinical significance and whether MP fluxes are secondary to pathophysiologic insults to the liver or might reflect compensatory responses.