title: Pancreatitis-associated protein protects the lung from leukocyte-induced injury.
abstract: BACKGROUND
  Severe pancreatitis is often complicated by shock and acute lung failure. Little is known about the pathophysiologic impact of the 16.6-kD lectine, named pancreatitis-associated protein (PAP), which is expressed during pancreatitis and which reduces mortality in a rat model with severe pancreatitis. Therefore, the aim of this study was to investigate the effects of PAP on the pulmonary vasculature after leukocyte activation with N-formyl-Met-Leu-Phe (fMLP).
  
  
  METHODS
  The experiments were performed in buffer-perfused isolated rabbit lungs. Mean pulmonary artery pressure, weight gain, and thromboxane A2 synthesis of the lungs were monitored. PAP was obtained by affinity chromatography of pancreas juice from pancreatitic rats. The authors tested whether treatment with PAP (260 microg/l, n = 9; or 500 microg/l, n = 6) before fMLP injection (10(-6) M) influences mean pulmonary artery pressure and edema formation. Lungs that were treated only with fMLP (n = 6) served as controls. Additional experiments in which PAP was applied were performed to study whether PAP (260 microg/l, n = 3; 500 microg/l, n = 3; 1,000 microg/l, n = 3) itself effects lung vasculature.
  
  
  RESULTS
  Application of fMLP resulted in an increase of mean pulmonary artery pressure (+/- SD) from 8 +/- 2 mmHg up to 26 +/-13 mmHg (P < 0.01) at a flow of 150 ml/min. Pretreatment with PAP reduced the peak pressure developed after fMLP to 15 +/- 7 mmHg (PAP 260 microg/l; P < 0.05) and to 9 +/- 4 mmHg (PAP 500 microg/l), respectively. In addition, the fMLP-induced lung weight gain of 9 +/- 7 g in the controls was prevented by pretreatment with PAP after 150 min in either concentration. In parallel to the attenuated pressure increase, thromboxane A2 release was significantly suppressed in the 260-microg/l (200 +/- 220 pmol x ml(-1) x min(-1); P < 0.01) and 500-microg/l (285 +/- 70 pmol x m(-1) x min(-1); P < 0.05) PAP groups compared with controls (1,138 +/- 800 pmol x ml(-1) x mi(-1)). Treatment with PAP alone in either concentration did not induce any changes in mean pulmonary artery pressure, weight gain, or thromboxane A2 release.
  
  
  CONCLUSIONS
  Clinically relevant concentrations of PAP prevented fMLP-induced vasoconstriction and edema formation in the lung. These findings point toward a protective effect of PAP on polymorphonuclear neutrophil leukocyte-mediated lung injury.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Dresden Germany. heller-a@rcs.urz.tu-dresden.de
authors.forename: A
authors.initials: A
authors.lastname: Heller
authors.forename: F
authors.initials: F
authors.lastname: Fiedler
authors.forename: J
authors.initials: J
authors.lastname: Schmeck
authors.forename: V
authors.initials: V
authors.lastname: Lück
authors.forename: J L
authors.initials: JL
authors.lastname: Iovanna
authors.forename: T
authors.initials: T
authors.lastname: Koch
mesh_terms: D000209:Acute-Phase Proteins / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D001794:Blood Pressure / Q000187:drug effects; D002846:Chromatography, Affinity; D066298:In Vitro Techniques; D037181:Lectins, C-Type; D007962:Leukocytes / Q000473:pathology*; D008168:Lung / Q000378:metabolism; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation; D009929:Organ Size / Q000187:drug effects; D000073718:Pancreatitis-Associated Proteins; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000187:drug effects; D011654:Pulmonary Edema / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000096:biosynthesis; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D000209:Acute-Phase Proteins; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; C000612144:Reg3b protein, rat; D013929:Thromboxane B2; D013928:Thromboxane A2; D009240:N-Formylmethionine Leucyl-Phenylalanine