title: Intestinal lymph-borne factors induce lung release of inflammatory mediators and expression of adhesion molecules after an intestinal ischemic insult.
abstract: BACKGROUND
  Intestinal ischemia and reperfusion (I/R) is a documented cause of acute lung injury (ALI) and systemic inflammation. We previously reported that obstruction of thoracic lymphatic flow during intestinal I/R blunts pulmonary neutrophil recruitment and microvascular injury and decreases the systemic levels of tumor necrosis factor. Here, we consider the existence of a gut-lung axis promoting the induction of systemic inflammation, whereby drained intestinal lymph stimulates lung expression of adhesion molecules and matrix components and generation of inflammatory mediators.
  
  
  METHODS
  Upon administration of anesthesia, male Wistar rats were subjected to occlusion of the superior mesenteric artery for 45 min, followed by 2 h of intestinal reperfusion (I/R); groups of rats were subjected to I/R with or without thoracic lymphatic duct ligation immediately before the procedure. The non-manipulated rats were used to investigate basal parameters.
  
  
  RESULTS
  Obstruction of thoracic lymphatic flow before intestinal I/R decreased the ability of cultured lung tissue explants to release IL-1β, IL-10, and VEGF. In contrast, lymphatic obstruction normalized the elevated lung expression of PECAM-1 caused by intestinal I/R. On the other hand, lung E-selectin expression was significantly reduced, whereas fibronectin expression and collagen synthesis were not affected. Lymph levels of LTB(4) and TXB(2) were found to be significantly increased.
  
  
  CONCLUSIONS
  These data suggest that lymph factors drained from the intestine during ischemic trauma stimulate the lung to generate inflammatory mediators and alter the expression of adhesion molecules. Disturbances in lung homeostasis mediated by lymph might contribute to the spread of inflammatory processes, thereby accounting for the systemic inflammation induced by intestinal I/R.
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Breithaupt-Faloppa
authors.forename: Luana Beatriz
authors.initials: LB
authors.lastname: Vitoretti
authors.forename: Gabriela
authors.initials: G
authors.lastname: Cavriani
authors.forename: Adriana
authors.initials: A
authors.lastname: Lino-dos-Santos-Franco
authors.forename: Lia Siguemi
authors.initials: LS
authors.lastname: Sudo-Hayashi
authors.forename: Ricardo Martins
authors.initials: RM
authors.lastname: Oliveira-Filho
authors.forename: B Boris
authors.initials: BB
authors.lastname: Vargaftig
authors.forename: Wothan
authors.initials: W
authors.lastname: Tavares-de-Lima
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D015777:Eicosanoids / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007422:Intestines / Q000098:blood supply* / Q000502:physiology*; D008026:Ligation; D008168:Lung / Q000378:metabolism*; D008208:Lymphatic System / Q000502:physiology* / Q000601:surgery; D008297:Male; D023421:Models, Animal; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D015777:Eicosanoids; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10