Schmelzle, Moritz2; Splith, Katrin2; Wiuff Andersen, Lars4; Kornek, Miroslaw2; Schuppan, Detlef2; Jones-Bamman, Caitlin2; Nowak, Martina2; Toxavidis, Vasilis2; D. Salhanick, Steven2; Han, Lihui2; am Schulte Esch, Jan2; Jonas, Sven2; W. Donnino, Michael2; C. Robson, Simon2
1 Department of Clinical Medicine - Anaesthesiology, Department of Clinical Medicine, Health, Aarhus University2 unknown3 Department of Clinical Medicine - Center for Akutforskning, Department of Clinical Medicine, Health, Aarhus University4 Department of Clinical Medicine - Center for Akutforskning, Department of Clinical Medicine, Health, Aarhus University
BACKGROUND: We have previously demonstrated that CD133 and CD39 are expressed by hematopoietic stem cells (HSC), which are mobilized after liver injury and target sites of injury, limit vascular inflammation, and boost hepatic regeneration. Plasma microparticles (MP) expressing CD39 can block endothelial activation. Here, we tested whether CD133 MP might be shed in a CD39-dependent manner in a model of liver injury and could potentially serve as biomarkers of liver failure in the clinic. METHODS: Wild-type and Cd39-null mice were subjected to acetaminophen-induced liver injury. Mice were sacrificed and plasma MP were isolated by ultracentrifugation. HSC and CD133 MP levels were analyzed by fluorescence-activated cell sorting. Patients were enrolled with acute (n=5) and acute on chronic (n=5) liver injury with matched controls (n=7). Blood was collected at admission and plasma CD133 and CD39 MP subsets were analyzed by fluorescence-activated cell sorting. RESULTS: HSC and CD133 MP levels were significantly increased only in the plasma of wild-type mice with acetaminophen hepatotoxicity (P<0.05). No increases in CD133 MP were noted in Cd39-null mice. Plasma MP increases were observed in patients with liver injury. These MP were characterized by significantly higher levels of CD39 (P<0.05). CONCLUSIONS: HSC and plasma CD133 MP levels increase in a CD39-dependent manner during experimental acute liver injury. Increased levels of CD39 MP are differentially noted in patients with liver injury. Further research is needed to determine whether MP fluxes are secondary to pathophysiologic insults to the liver or might reflect compensatory responses.