title: Alveolar macrophage secretory products augment the response of rat pulmonary artery endothelial cells to hypoxia and reoxygenation.
abstract: BACKGROUND
  Endothelial cell activation is an important response to ischemia and reperfusion in a variety of vascular beds. Endothelial cells secrete a multitude of proinflammatory mediators and express adhesion molecules that promote leukocyte recruitment into injured tissues. Pulmonary artery endothelial cell response to lung ischemia-reperfusion injury does not appear robust enough to drive the development of lung injury independently. Rather, the alveolar macrophage is the key cell in the development of ischemia-reperfusion injury of the lung. Macrophages are known to be a rich source of inflammatory mediators, but the precise mechanism whereby they amplify injury is unknown. The aim of this study was to determine whether alveolar macrophage secretory products amplify the response of the endothelial cell using an in vitro model of lung reperfusion injury.
  
  
  METHODS
  Macrophages were exposed to hypoxia and reoxygenation and the media collected. Cultured endothelial cells were then exposed to macrophage media and maintained at normoxia or subjected to hypoxia and reoxygenation. To assess any reciprocal effects of endothelial cell products on macrophage activation, macrophages were likewise exposed to activated endothelial cell media.
  
  
  RESULTS
  Exposure of endothelial cells to activated alveolar macrophage media enhanced chemokine secretion in response to hypoxia and reoxygenation. In the reciprocal experiment, activated endothelial cell media increased the production of macrophage inflammatory protein 1alpha from macrophages.
  
  
  CONCLUSIONS
  Alveolar macrophages drive the development of lung reperfusion injury, by enhancing the production of proinflammatory chemokines from endothelial cells, which impart a degree of positive feedback on alveolar macrophages.
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, University of Washington Medical Center, Seattle, Washington 98195, USA.
authors.forename: Anton S
authors.initials: AS
authors.lastname: McCourtie
authors.forename: Heather E
authors.initials: HE
authors.lastname: Merry
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Farivar
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Goss
authors.forename: Michael S
authors.initials: MS
authors.lastname: Mulligan
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D042783:Endothelial Cells / Q000276:immunology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000276:immunology*; D008171:Lung Diseases / Q000276:immunology*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D010100:Oxygen / Q000502:physiology; D011650:Pulmonary Alveoli / Q000276:immunology*; D011651:Pulmonary Artery / Q000166:cytology* / Q000276:immunology*; D051381:Rats; D020318:Rats, Long-Evans; D015427:Reperfusion Injury / Q000276:immunology*
chemical_list: D018925:Chemokines; D010100:Oxygen