Document Detail

Pancreatitis-associated protein protects the lung from leukocyte-induced injury.
MedLine Citation:
PMID:  10551593     Owner:  NLM     Status:  MEDLINE    
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. CONCLUSION: 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.
A Heller; F Fiedler; J Schmeck; V L?ck; J L Iovanna; T Koch
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anesthesiology     Volume:  91     ISSN:  0003-3022     ISO Abbreviation:  Anesthesiology     Publication Date:  1999 Nov 
Date Detail:
Created Date:  1999-11-24     Completed Date:  1999-11-24     Revised Date:  2010-02-08    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1408-14     Citation Subset:  AIM; IM    
Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Dresden Germany.
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MeSH Terms
Acute-Phase Proteins / isolation & purification,  pharmacology,  therapeutic use*
Antigens, Neoplasm*
Blood Pressure / drug effects
Chromatography, Affinity
Lectins, C-Type*
Leukocytes / pathology*
Lung / metabolism
N-Formylmethionine Leucyl-Phenylalanine / pharmacology
Neutrophil Activation
Organ Size / drug effects
Pulmonary Artery / drug effects,  physiopathology
Pulmonary Circulation / drug effects
Pulmonary Edema / pathology,  physiopathology,  prevention & control*
Rats, Sprague-Dawley
Thromboxane A2 / biosynthesis
Thromboxane B2 / biosynthesis
Tumor Markers, Biological*
Vasoconstriction / drug effects*
Reg. No./Substance:
0/Acute-Phase Proteins; 0/Antigens, Neoplasm; 0/Lectins, C-Type; 0/Tumor Markers, Biological; 0/pancreatitis-associated protein; 54397-85-2/Thromboxane B2; 57576-52-0/Thromboxane A2; 59880-97-6/N-Formylmethionine Leucyl-Phenylalanine

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