title: Lipopolysaccharide and hemorrhagic shock cause systemic inflammation by different mechanisms.
abstract: BACKGROUND
  Hemorrhagic shock (HS) and sepsis are common after trauma. These trauma patients often need ventilatory support. The resulting hyperinflammatory state can cause neutrophil-mediated complications such as adult respiratory distress syndrome. An important underlying mechanism is polymorphonuclear neutrophil (PMN) priming by damage-associated molecular patterns (DAMPs, caused by, e.g., HS and ventilation) and by pathogen-associated molecular patterns (PAMPs, e.g., lipopolysaccharide [LPS] in sepsis). The aim of this study was to compare the inflammatory response induced by DAMPs (liberated during HS) and PAMPs (LPS challenge) under conditions of high-volume ventilation.
  
  
  METHODS
  Twenty-seven male Sprague-Dawley rats were randomized for mechanical ventilation (MV) alone (9 rats; positive end-expiratory pressure, 5 cm H2O; pressure control, +20 cm H2O; FIO2, 0.33), MV + HS (9 rats; hemorrhage, 30% volume loss) or MV + LPS (9 rats, LPS, 5mg/kg intravenously administered). Five rats were used as controls. Total PMN count and differentials were determined. In addition, the expression of activation markers (CD62L and CD11b) on blood-derived PMNs was measured by flow cytometry. Pulmonary inflammatory response was measured by PMN counts in bronchoalveolar fluid. The presence of neutrophils in the lung was determined by total myeloperoxidase. Results are expressed as means ± SEM; p ≤ 0.05 is considered statistically significant.
  
  
  RESULTS
  All treated rats had more neutrophils in the blood and bronchoalveolar fluid compared with the controls. Myeloperoxidase was significantly higher in all groups compared with controls. MV and MV + HS rats had more blood neutrophils with CD62L(bright)/CD11b(dim) phenotypes, whereas MV + LPS rats showed more CD62L(dim)/CD11b(bright) neutrophils, indicative for activated cells.
  
  
  CONCLUSIONS
  All ventilated rats showed a systemic inflammatory response. The responses to HS and MV were very similar, suggesting a common pathway of DAMP-associated inflammation. In marked contrast, LPS showed a different neutrophil phenotype (CD62L(dim)/CD11b(bright)), suggesting a different inflammatory response. It is concluded that shock induced by DAMPs and PAMPs have different underlying mechanisms.
authors.affiliation: Department of Trauma Surgery, University Medical Center Utrecht, Utrecht, the Netherlands. kwessem@umcutrecht.nl
authors.forename: K J P
authors.initials: KJ
authors.lastname: van Wessem
authors.forename: M
authors.initials: M
authors.lastname: Heeres
authors.forename: P H C
authors.initials: PH
authors.lastname: Leliefeld
authors.forename: L
authors.initials: L
authors.lastname: Koenderman
authors.forename: L P H
authors.initials: LP
authors.lastname: Leenen
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D039481:CD11b Antigen / Q000032:analysis; D004731:Endotoxins / Q000494:pharmacology; D019041:L-Selectin / Q000032:analysis; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000201:enzymology; D008297:Male; D009504:Neutrophils / Q000276:immunology; D009195:Peroxidase / Q000032:analysis; D011175:Positive-Pressure Respiration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D018746:Systemic Inflammatory Response Syndrome / Q000503:physiopathology*
chemical_list: D039481:CD11b Antigen; D004731:Endotoxins; D008070:Lipopolysaccharides; D019041:L-Selectin; C044101:endotoxin, Escherichia coli; D009195:Peroxidase