title: A novel therapeutic strategy for attenuating neutrophil-mediated lung injury in vivo.
abstract: OBJECTIVE
  To evaluate the effect of inhalation of aerosolized opsonized dead Escherichia coli on inflammatory pulmonary neutrophil (PMN) apoptosis, lung injury, and survival in a PMN-mediated lung injury model in vivo.
  
  
  BACKGROUND
  Neutrophils that have transmigrated into an inflammatory focus display increased functional capacity and delayed apoptosis, resulting in an increased capacity to injure normal host tissue. The authors have previously shown that E. coli induces PMN apoptosis in vitro.
  
  
  METHODS
  Lung injury mediated by PMNs was established by aortic occlusion and reperfusion. Adult male Sprague-Dawley rats were randomized into four groups: sham ischemia-reperfusion (I/R) treated with intratracheal inhalation of aerosolized normal saline, I/R treated with aerosolized normal saline intratracheally, I/R treated with aerosolized opsonized dead E. coli intratracheally, and I/R treated with aerosolized opsonized dead E. coli and the caspase inhibitor zVAD-FMK intratracheally 5 minutes before reperfusion. Both systemic and bronchoalveolar lavage PMNs were isolated and apoptosis was quantified at 0, 6, 12, 18, and 24 hours. Lung injury parameters including wet/dry lung weight ratio, histology, myeloperoxidase activity, and protein content were also assessed. In addition, a survival study was performed, both in a prophylactic and in a therapeutic setting.
  
  
  RESULTS
  Administration of aerosolized dead E. coli before the reperfusion injury induced pulmonary PMN apoptosis and reversed the delayed apoptosis evident in the I/R plus normal saline group. There was also a significant improvement in lung injury parameters as well as in survival, both prophylactically as well as therapeutically.
  
  
  CONCLUSIONS
  Directly modulating PMN cell death represents a novel mechanism for attenuating PMN-mediated lung injury and may ultimately benefit the outcome in patients with adult respiratory distress syndrome.
authors.affiliation: Department of Surgery, National University of Ireland, University College Cork/Cork University Hospital, Cork, Ireland.
authors.forename: Shastri
authors.initials: S
authors.lastname: Sookhai
authors.forename: Jiang Juai
authors.initials: JJ
authors.lastname: Wang
authors.forename: Morgan
authors.initials: M
authors.lastname: McCourt
authors.forename: William
authors.initials: W
authors.lastname: Kirwan
authors.forename: David
authors.initials: D
authors.lastname: Bouchier-Hayes
authors.forename: Paul
authors.initials: P
authors.lastname: Redmond
mesh_terms: D000818:Animals; D017209:Apoptosis; D004926:Escherichia coli; D008168:Lung / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D023421:Models, Animal; D009504:Neutrophils / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*