title: Tumor necrosis factor-alpha from resident lung cells is a key initiating factor in pulmonary ischemia-reperfusion injury.
abstract: OBJECTIVE
  A central role of macrophages in initiating lung ischemia-reperfusion injury is emerging. Tumor necrosis factor-alpha is a proinflammatory cytokine secreted mainly by macrophages under various conditions. We hypothesized that tumor necrosis factor-alpha from resident lung cells is a key initiating factor in pulmonary ischemia-reperfusion injury.
  
  
  METHODS
  We used an isolated, buffer-perfused lung system to explore the role of tumor necrosis factor-alpha production by resident lung cells in pulmonary ischemia-reperfusion injury. Lungs from wild-type mice and tumor necrosis factor-alpha-deficient mice were subjected to 60 minutes of ischemia followed by 60 minutes of reperfusion. Histologic injury scores and measurements of lung compliance, airway resistance, mean pulmonary artery pressure, vascular reactivity, and wet lung weight index were obtained and compared using repeated-measures analysis of variance.
  
  
  RESULTS
  Lungs from tumor necrosis factor-alpha-deficient mice showed significantly less injury in all physiologic parameters throughout the entire 60 minutes of reperfusion compared with lungs from wild-type mice (P <.001). The most notable effects were observed in pulmonary artery pressure and airway resistance. Vascular reactivity (acute vasoconstrictive episodes per 60 minutes) was also blunted in the lungs from tumor necrosis factor-alpha-deficient mice compared with the lungs from wild-type mice (5.8 responses/hour vs 1.2 responses). Histologic injury scores and wet lung weight index were significantly reduced in lungs from tumor necrosis factor-alpha-deficient mice.
  
  
  CONCLUSIONS
  By using the advantages of a nonblood-perfused system, we have focused our investigation on resident lung cells. Our results demonstrate that resident cell-produced tumor necrosis factor-alpha is a key initiating factor in acute lung ischemia-reperfusion injury.
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, University of Virginia Health System, Charlottesville 22908, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Maxey
authors.forename: Richard I
authors.initials: RI
authors.lastname: Enelow
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gaston
authors.forename: Irving L
authors.initials: IL
authors.lastname: Kron
authors.forename: Victor E
authors.initials: VE
authors.lastname: Laubach
authors.forename: Allan
authors.initials: A
authors.lastname: Doctor
mesh_terms: D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015601:Injury Severity Score; D008168:Lung / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D008170:Lung Compliance / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008955:Models, Cardiovascular; D009929:Organ Size; D011654:Pulmonary Edema / Q000378:metabolism; D011669:Pulmonary Wedge Pressure / Q000187:drug effects / Q000502:physiology; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D013223:Statistics as Topic; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha