title: Role of protease-activated receptor 2 in lung injury development during acute pancreatitis in rats.
abstract: OBJECTIVE
  The objective of this study was to evaluate whether an uncontrolled activation of mast cells and macrophages through protease-activated receptor-2 (PAR-2) during acute pancreatitis could develop lung injury.
  
  
  METHODS
  Pancreatitis was induced in rats by intraductal infusion of sodium taurocholate. In a group of animals, PAR-2 antagonist or trypsin (TRP) inhibitor was intravenously administered before the pancreatitis induction. In additional groups, the animals were treated with PAR-2-activating peptide or pancreatic TRP. The myeloperoxidase (MPO) activity was measured to evaluate the progression of inflammation.
  
  
  RESULTS
  Plasma from the animals with pancreatitis and pancreatic TRP induced the secretion of mast cells and alveolar macrophages as well as increased the density of PAR-2 in the plasma membrane. The treatment of alveolar macrophages with TRP, tryptase, as well as PAR-1- and PAR-2-activating peptide led to an increase in calcium-triggered exocytosis. Similar results were obtained in acinar cells. The intravenous injection of PAR-2-activating peptide and TRP induced an increase in MPO activity in the lung. The intravenous injection of PAR-2 antagonist or TRP inhibitor before the pancreatitis induction could prevent the increase in MPO activity in the pancreas and the lung.
  
  
  CONCLUSIONS
  The TRP generated during acute pancreatitis could be involved in the progression of lung injury through the activation of PAR-2 in alveolar macrophages.
authors.affiliation: From the *Unidad de Gastroenterología, Hospital General Universitario de Alicante; †Instituto de Neurociencias, Universidad Miguel Hernández-Consejo Superior Investigaciones Científicas, Alicante; ‡Departamento de Patología Experimental, Instituto de Investigaciones Biomédicas de Barcelona-Consejo Superior Investigaciones Científicas, Insitut d'Investigacions Biomédiques August Pi i Sunyer, and Centro Investigación Biomédica en Red: Enfermedades Hepáticas y Digestivas, Barcelona; §Universidad Miguel Hernández, Elche; and ∥Centro Investigación Biomédica en Red: Enfermedades Neurodegenerativas, Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: de-Madaria
authors.forename: María
authors.initials: M
authors.lastname: del Mar Francés
authors.forename: Sabrina
authors.initials: S
authors.lastname: Gea-Sorlí
authors.forename: Luis M
authors.initials: LM
authors.lastname: Gutiérrez
authors.forename: Salvador
authors.initials: S
authors.lastname: Viniegra
authors.forename: Miguel
authors.initials: M
authors.lastname: Pérez-Mateo
authors.forename: Daniel
authors.initials: D
authors.lastname: Closa
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Lopez-Font
mesh_terms: D061354:Acinar Cells / Q000187:drug effects / Q000378:metabolism; D000208:Acute Disease; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D005089:Exocytosis / Q000187:drug effects; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008171:Lung Diseases / Q000378:metabolism* / Q000503:physiopathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D018613:Microscopy, Confocal; D009842:Oligopeptides / Q000494:pharmacology; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D009195:Peroxidase / Q000378:metabolism; D017208:Rats, Wistar; D044464:Receptor, PAR-2 / Q000378:metabolism* / Q000502:physiology; D013656:Taurocholic Acid; D014357:Trypsin / Q000378:metabolism / Q000494:pharmacology
chemical_list: D009842:Oligopeptides; D044464:Receptor, PAR-2; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; D013656:Taurocholic Acid; D009195:Peroxidase; D014357:Trypsin; D002118:Calcium