title: Aspirin, but Not Tirofiban Displays Protective Effects in Endotoxin Induced Lung Injury.
abstract: BACKGROUND
  Treatment of acute lung injury (ALI) remains an unsolved problem in intensive care medicine. Recruitment of neutrophils into the lungs, regarded as a key mechanism in progression of ALI, depends on signaling between neutrophils and platelets. Consequently we explored the effect of platelet-targeted aspirin and tirofiban treatment in endotoxin induced acute lung injury.
  
  
  METHODS
  C57Bl/6 mice were exposed to aerosolized LPS (500μg/ml) for 30min and treated with Aspirin (100μg/g bodyweight via intraperitoneal injection, 30 min before or 1 hour after LPS inhalation) or Tirofiban (0.5μg/ g bodyweight via tail vein injection 30 min before or 1 hour after LPS inhalation). The count of alveolar, interstitial, and intravascular neutrophils was assessed 4h later by flow cytometry. Lung permeability changes were assessed by FITC-dextran clearance and protein content in the BAL fluid.
  
  
  RESULTS
  Aspirin both before and after LPS inhalation reduced neutrophil influx into the lung and lung permeability indicating the protective role of Aspirin in ALI. Tirofiban, however, did not alter neutrophil recruitment after LPS inhalation. Release of platelet-derived chemokines CCL5 and PF4 and neutrophil extracellular traps was reduced by Aspirin but not by Tirofiban.
  
  
  CONCLUSIONS
  Aspirin, but not Tirofiban reduces neutrophil recruitment and displays protective effects during endotoxin induced lung injury.
authors: European Vascular Center Aachen-Maastricht, Rhenish Westphalian Technical University Aachen, Aachen Germany.
authors: Jessica
authors: J
authors: Tilgner
authors: European Vascular Center Aachen-Maastricht, Rhenish Westphalian Technical University Aachen, Aachen Germany.
authors: Klaus Thilo
authors: KT
authors: von Trotha
authors: European Vascular Center Aachen-Maastricht, Rhenish Westphalian Technical University Aachen, Aachen Germany.
authors: Alexander
authors: A
authors: Gombert
authors: European Vascular Center Aachen-Maastricht, Rhenish Westphalian Technical University Aachen, Aachen Germany.|Maastricht University Medical Center, Maastricht, The Netherlands.
authors: Michael J
authors: MJ
authors: Jacobs
authors: Institute for Cardiovascular Prevention, Ludwig Maximillian University Munich, Munich, Germany.|German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.
authors: Maik
authors: M
authors: Drechsler
authors: Institute for Cardiovascular Prevention, Ludwig Maximillian University Munich, Munich, Germany.|German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.
authors: Yvonne
authors: Y
authors: Döring
authors: Institute for Cardiovascular Prevention, Ludwig Maximillian University Munich, Munich, Germany.|Department of Pathology, University of Amsterdam, Amsterdam, The Netherlands.|German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.
authors: Oliver
authors: O
authors: Soehnlein
authors: European Vascular Center Aachen-Maastricht, Rhenish Westphalian Technical University Aachen, Aachen Germany.|Institute for Cardiovascular Prevention, Ludwig Maximillian University Munich, Munich, Germany.
authors: Jochen
authors: J
authors: Grommes
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D004731:Endotoxins / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000473:pathology; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D004731:Endotoxins; D014443:Tyrosine; D000077466:Tirofiban