title: Comparison of the effect of LPS and PAM3 on ventilated lungs.
abstract: BACKGROUND
  While lipopolysaccharide (LPS) from Gram-negative bacteria has been shown to augment inflammation in ventilated lungs information on the effect of Gram-positive bacteria is lacking. Therefore the effect of LPS and a lipopetide from Gram-positive bacteria, PAM3, on ventilated lungs were investigated.
  
  
  METHODS
  C57/Bl6 mice were mechanically ventilated. Sterile saline (sham) and different concentrations of LPS (1 microg and 5 microg) and PAM3 (50 nM and 200 nM) were applied intratracheally. Lung function parameters and expression of MIP-2 and TNFalpha as well as influx of neutrophils were measured.
  
  
  RESULTS
  Mechanical ventilation increased resistance and decreased compliance over time. PAM3 but not LPS significantly increased resistance compared to sham challenge (P < 0.05). Both LPS and PAM3 significantly increased MIP-2 and TNFalpha mRNA expression compared to sham challenge (P < 0.05). The numbers of neutrophils were significantly increased after LPS at a concentration of 5 microg compared to sham (P < 0.05). PAM3 significantly increased the numbers of neutrophils at both concentrations compared to sham (P < 0.05).
  
  
  CONCLUSIONS
  These data suggest that PAM3 similar to LPS enhances ventilator-induced inflammation. Moreover, PAM3 but not LPS increases pulmonary resistance in ventilated lungs. Further studies are warranted to define the role of lipopetides in ventilator-associated lung injury.
authors.affiliation: Pathophysiology of Inflammation, Research Center Borstel, Borstel, Germany. hphauber@fz-borstel.de
authors.forename: Hans P
authors.initials: HP
authors.lastname: Hauber
authors.forename: Dörte
authors.initials: D
authors.lastname: Karp
authors.forename: Torsten
authors.initials: T
authors.lastname: Goldmann
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Vollmer
authors.forename: Peter
authors.initials: P
authors.lastname: Zabel
mesh_terms: D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000818:Animals; D054426:Chemokine CXCL2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006090:Gram-Negative Bacteria / Q000378:metabolism*; D006094:Gram-Positive Bacteria / Q000378:metabolism*; D055666:Lipopeptides / Q000378:metabolism / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology*; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008170:Lung Compliance / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D012121:Respiration, Artificial; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D055666:Lipopeptides; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha
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