title: Involvement of Akt and endothelial nitric oxide synthase in ventilation-induced neutrophil infiltration: a prospective, controlled animal experiment.
abstract: BACKGROUND
  Positive pressure ventilation with large tidal volumes has been shown to cause release of cytokines, including macrophage inflammatory protein-2 (MIP-2), a functional equivalent of human IL-8, and neutrophil infiltration. Hyperoxia has been shown to increase ventilator-induced lung injury, but the mechanisms regulating interaction between a large tidal volume and hyperoxia are unclear. We hypothesized that large tidal volume ventilation using hyperoxia would increase MIP-2 production and neutrophil infiltration via the serine/threonine kinase/protein kinase B (Akt) pathway and the endothelial nitric oxide synthase (eNOS) pathway.
  
  
  METHODS
  C57BL/6 mice were exposed to large tidal volume (30 ml/kg) mechanical ventilation with room air or hyperoxia for 1-5 hours.
  
  
  RESULTS
  Large tidal volume ventilation using hyperoxia induced neutrophil migration into the lung, MIP-2 production, and Akt and eNOS activation in a time-dependent manner. Both the large tidal volume ventilation of Akt mutant mice and the pharmacological inhibition of Akt with LY294002 attenuated neutrophil sequestration, MIP-2 protein production, and Akt and eNOS activation.
  
  
  CONCLUSIONS
  We conclude that hyperoxia increased large tidal volume-induced MIP-2 production and neutrophil influx through activation of the Akt and eNOS pathways.
authors: Division of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, and Chang Gung University, Kweishan, Taoyuan 333, Taiwan.
authors: Li-Fu
authors: LF
authors: Li
authors: Shuen-Kuei
authors: SK
authors: Liao
authors: Cheng-Huei
authors: CH
authors: Lee
authors: Chung-Chi
authors: CC
authors: Huang
authors: Deborah A
authors: DA
authors: Quinn
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018496:Hyperoxia / Q000209:etiology / Q000378:metabolism; D008168:Lung / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011897:Random Allocation; D012016:Reference Values; D012121:Respiration, Artificial / Q000009:adverse effects*
chemical_list: D016207:Cytokines; D052250:Nitric Oxide Synthase Type III; D017346:Protein Serine-Threonine Kinases
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