title: Alveolar macrophage secretory products effect type 2 pneumocytes undergoing hypoxia-reoxygenation.
abstract: BACKGROUND
  Activation of the alveolar macrophage is centrally important to the development of lung ischemia reperfusion injury. Alveolar macrophages and type 2 pneumocytes secrete a variety of proinflammatory mediators in response to oxidative stress. The manner in which they interact and how the macrophage may influence pneumocyte responses in lung ischemia reperfusion injury is unknown. Utilizing an in vitro model of hypoxia and reoxygenation, we sought to determine if the proinflammatory response of type 2 pneumocytes to oxidative stress would be amplified by alveolar macrophage secretory products.
  
  
  METHODS
  Cultured pneumocytes were exposed to control media or media from cultured macrophages exposed to hypoxia and reoxygenation. Pneumocytes were subsequently subjected to hypoxia and reoxygenation and assessed for both nuclear translocation of nuclear factor kappa B and inflammatory cytokine and chemokine secretion. To examine for any reciprocal interactions, we reversed the experiment, exposing macrophages to conditioned pneumocyte media.
  
  
  RESULTS
  In the presence of media from stimulated macrophages, production of proinflammatory mediators by type 2 pneumocytes was dramatically enhanced. In contrast, exposure of the macrophage to conditioned pneumocyte media had an inhibitory effect on macrophage responses subsequently exposed to hypoxia and reoxygenation.
  
  
  CONCLUSIONS
  The alveolar macrophage drives the development of lung reperfusion injury in part through amplification of the inflammatory response of type 2 pneumocytes subjected to hypoxia and reoxygenation.
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, University of Washington Medical Center, Seattle, Washington, USA.
authors.forename: Anton S
authors.initials: AS
authors.lastname: McCourtie
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Farivar
authors.forename: Steven M
authors.initials: SM
authors.lastname: Woolley
authors.forename: Heather E
authors.initials: HE
authors.lastname: Merry
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Wolf
authors.forename: Brendan
authors.initials: B
authors.lastname: Mackinnon-Patterson
authors.forename: John C
authors.initials: JC
authors.lastname: Keech
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fitzsullivan
authors.forename: Michael S
authors.initials: MS
authors.lastname: Mulligan
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008262:Macrophage Activation / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D010100:Oxygen / Q000494:pharmacology*; D011336:Probability; D051381:Rats; D020318:Rats, Long-Evans; D012016:Reference Values; D015427:Reperfusion Injury / Q000503:physiopathology; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018925:Chemokines; D017077:Culture Media, Conditioned; D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D010100:Oxygen