title: Hydroxyethyl starch 130/0.4 decreases inflammation, neutrophil recruitment, and neutrophil extracellular trap formation.
abstract: BACKGROUND
  During systemic inflammation, leucocytes are activated and extravasate into damaged tissue. Activation and recruitment are influenced by different mechanisms, including the interaction of leucocytes with platelets and neutrophil extracellular traps (NET) formation. Here, we investigated the molecular mechanism by which hydroxyethyl starch (HES 130/0.4) dampens systemic inflammation in vivo.
  
  
  METHODS
  Systemic inflammation was induced in C57Bl/6 wild-type mice by caecal ligation and puncture and cytokine concentrations in the blood, neutrophil recruitment, platelet-neutrophil aggregates, and NET formation were investigated in vivo. Intravascular adherent and transmigrated neutrophils were analysed by intravital microscopy (IVM) of the cremaster muscle and the kidneys. Flow chamber assays were used to investigate the different steps of the leucocyte recruitment cascade.
  
  
  RESULTS
  By using flow cytometry, we demonstrated that HES 130/0.4 reduces neutrophil recruitment into the lung, liver, and kidneys during systemic inflammation (n=8 mice per group). IVM revealed a reduced number of adherent and transmigrated neutrophils in the cremaster and kidney after HES 130/0.4 administration (n=8 mice per group). Flow chamber experiments showed that HES 130/0.4 significantly reduced chemokine-induced neutrophil arrest (n=4 mice per group). Furthermore, HES 130/0.4 significantly reduced the formation of platelet-neutrophil aggregates, and NET formation during systemic inflammation (n=8 mice per group).
  
  
  CONCLUSIONS
  Our findings suggest that HES 130/0.4 significantly reduces neutrophil-platelet aggregates, NET formation, chemokine-induced arrest, and transmigration of neutrophils under inflammatory conditions.
authors.affiliation: Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Rossaint
authors.affiliation: Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Berger
authors.affiliation: Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Kraft
authors.affiliation: Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Van Aken
authors.affiliation: Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Giesbrecht
authors.affiliation: Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany zarbock@uni-muenster.de.
authors.forename: A
authors.initials: A
authors.lastname: Zarbock
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D065206:Extracellular Traps / Q000187:drug effects*; D005434:Flow Cytometry / Q000379:methods; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects* / Q000276:immunology; D010952:Plasma Substitutes / Q000494:pharmacology*
chemical_list: C485123:HES 130-0.4; D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes
keywords: HES 130/0.4; inflammation; leucocyte; neutrophil extracellular traps; platelet