title: Increased plasma levels of microparticles expressing CD39 and CD133 in acute liver injury.
abstract: 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.
authors.affiliation: The Transplant Institute and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA. moritz.schmelzle@medizin.uni-leipzig.de
authors.forename: Moritz
authors.initials: M
authors.lastname: Schmelzle
authors.forename: Katrin
authors.initials: K
authors.lastname: Splith
authors.forename: Lars W
authors.initials: LW
authors.lastname: Andersen
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Kornek
authors.forename: Detlef
authors.initials: D
authors.lastname: Schuppan
authors.forename: Caitlin
authors.initials: C
authors.lastname: Jones-Bamman
authors.forename: Martina
authors.initials: M
authors.lastname: Nowak
authors.forename: Vasilis
authors.initials: V
authors.lastname: Toxavidis
authors.forename: Steven D
authors.initials: SD
authors.lastname: Salhanick
authors.forename: Lihui
authors.initials: L
authors.lastname: Han
authors.forename: Jan
authors.initials: J
authors.lastname: Schulte am  Esch
authors.forename: Sven
authors.initials: S
authors.lastname: Jonas
authors.forename: Michael W
authors.initials: MW
authors.lastname: Donnino
authors.forename: Simon C
authors.initials: SC
authors.lastname: Robson
mesh_terms: D000071916:AC133 Antigen; D000082:Acetaminophen / Q000633:toxicity; D055371:Acute Lung Injury / Q000097:blood*; D000818:Animals; D015703:Antigens, CD / Q000097:blood*; D001081:Apyrase / Q000097:blood*; D015415:Biomarkers; D055252:Cell-Derived Microparticles / Q000737:chemistry* / Q000502:physiology; D006023:Glycoproteins / Q000097:blood*; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D015415:Biomarkers; D006023:Glycoproteins; D016209:Interleukin-8; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D042461:Vascular Endothelial Growth Factor A; D000082:Acetaminophen; D001081:Apyrase; C067869:CD39 antigen