title: Microparticle generation and leucocyte death in Shiga toxin-mediated HUS.
abstract: BACKGROUND
  Shiga toxin-induced haemolytic uraemic syndrome (STEC-HUS) is an acute multisystem disorder characterized by renal failure, neurological dysfunction, haemolysis and intravascular thrombosis. Circulating microparticles originating from a number of cell types including thrombocytes and leucocytes are elevated in paediatric patients. In vitro data also suggest modification of leucocyte death by Shiga toxin. Here, we investigated microparticle generation and leucocyte cell death in vivo in adult STEC-HUS patients during acute disease and recovery.
  
  
  METHODS
  Multi-colour flow cytometry and immunofluorescence were used to assess microparticle concentration and provenience thrombocyte microparticle seeding to leucocytes and leucocyte cell death in adult STEC-HUS patients treated at a tertiary care centre during the STEC-HUS outbreak in Germany in 2011.
  
  
  RESULTS
  Plasma microparticle concentrations of both platelet and leucocyte origin were elevated during acute STEC-HUS. Platelet microparticles (MP) were detected on a high proportion of monocytes and granulocytes. Among therapeutic interventions, plasma exchange reduced platelet marker expression on leucocytes, inhibition of complement had only moderate impact on the number of circulating MP and did not alter platelet microparticle binding to leucocytes. Numbers of apoptotic and necrotic monocytes and granulocytes were significantly increased in patients with STEC-HUS compared to healthy controls. Complement inhibition significantly increased the number of circulating apoptotic cells. Monocyte apoptosis on admission was significantly higher in patients subsequently assigned to plasma exchange or admitted to the intensive care unit.
  
  
  CONCLUSIONS
  In STEC-HUS, elevated numbers of circulating MP and dead leucocytes were detected. Monocyte and granulocyte deaths are novel markers of acute STEC-HUS that may actively contribute to tissue destruction by liberation of pro-inflammatory enzymes and cytokines.
authors.affiliation: Department of Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Shuwang
authors.initials: S
authors.lastname: Ge
authors.forename: Barbara
authors.initials: B
authors.lastname: Hertel
authors.forename: Sang Hi
authors.initials: SH
authors.lastname: Emden
authors.forename: Jan
authors.initials: J
authors.lastname: Beneke
authors.forename: Jan
authors.initials: J
authors.lastname: Menne
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Sibylle
authors.initials: S
authors.lastname: von Vietinghoff
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000473:pathology; D002478:Cells, Cultured; D015331:Cohort Studies; D004196:Disease Outbreaks; D004927:Escherichia coli Infections / Q000139:chemically induced / Q000382:microbiology / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006463:Hemolytic-Uremic Syndrome / Q000139:chemically induced / Q000382:microbiology / Q000473:pathology*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000473:pathology; D009336:Necrosis; D022621:Shiga Toxin / Q000009:adverse effects*; D054323:Shiga-Toxigenic Escherichia coli / Q000472:pathogenicity*; D062606:Tertiary Care Centers
chemical_list: D015415:Biomarkers; D022621:Shiga Toxin