Proteinase-free myeloperoxidase increases airway epithelial permeability in a whole trachea model

In cystic fibrosis the bronchiectatic conducting airways have large numbers of neutrophils in their walls and in their luminal contents. The neutrophil's primary granule enzyme activities of elastase and peroxidase are increased in the sputum of these patients. It has been postulated that these...

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Published in:	Pediatric pulmonology Vol. 24; no. 1; pp. 29 - 34
Main Authors:	Regelmann, Warren E., Schneider, Lisa A., Fahrenkrug, Scott C., Gray, Beulah H., Johnson, Stephanie, Herron, Jean M., Clawson, C. Carlyle, Clawson, Dawn J., Wangensteen, O. Douglas
Format:	Journal Article
Language:	English
Published:	New York Wiley Subscription Services, Inc., A Wiley Company 01-07-1997 Wiley-Liss
Subjects:	airway epithelium Animals Biological and medical sciences bronchiectasis Cell Membrane Permeability - physiology cystic fibrosis Cystic Fibrosis - enzymology Disease Models, Animal electron microscopy Epithelium - enzymology Epithelium - physiology Gastroenterology. Liver. Pancreas. Abdomen Humans Liver. Biliary tract. Portal circulation. Exocrine pancreas Medical sciences myeloperoxidase neutrophil granules Neutrophils - enzymology Neutrophils - physiology Other diseases. Semiology Peroxidase - metabolism proteases Rats Rats, Sprague-Dawley Sputum - enzymology Trachea - cytology Trachea - enzymology Rat Isolated organ Enzymatic activity Bronchus disease Complication Peroxidase Trachea Pancreatic disease Pathophysiology Respiratory disease Enzyme Respiratory epithelium Rodentia Metabolic diseases Exploration Cystic fibrosis Bronchiectasis Permeability Electron microscopy In vitro Genetic disease Pathology Peptidases Vertebrata Mammalia Peroxidases Animal Digestive diseases Hydrolases Oxidoreductases
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Summary:	In cystic fibrosis the bronchiectatic conducting airways have large numbers of neutrophils in their walls and in their luminal contents. The neutrophil's primary granule enzyme activities of elastase and peroxidase are increased in the sputum of these patients. It has been postulated that these enzymes—together or individually—act to damage the airway epithelium. However, only peroxidase activity has consistently correlated with the degree of structural and functional airway disease in these patients with leakage of plasma protein into the airway lumen (Regelmann et al., Pediatr Pulmonol. 1995; 19: 1–9). The present study was designed to test whether human neutrophil‐derived myeloperoxidase can independently produce bronchial epithelial damage without the presence of proteases, as measured by increased permeability of the airway epithelium. Human peripheral blood neutrophils were purified, their primary granules isolated, and their peroxidase purified using affinity and ion exchange column chromatography. Activity of the proteinase‐free peroxidase was measured using a chromogenic substrate. The effect of this peroxidase on the permeability of excised rat tracheas was measured using radioactive and fluorescent‐labeled non‐ionic molecules of varying molecular weight. Rat tracheas exposed to 15 minute treatments with either 130 U of peroxidase or hydrogen peroxide (10−5 M) did not show a significant increase in the permeability of the epithelium to [3H]inulin, [14C]sucrose, and fluorescein isothiocyanate dextran 20 compared with control tracheas. However, those tracheas exposed to 130 U peroxidase followed by 10−5 M hydrogen peroxide showed an increased permeability to each of the three test solutes. We conclude that proteinase‐free myeloperoxidase, in the presence of non‐toxic concentrations of its substrates, hydrogen peroxide and halide, produced increases in permeability to non‐ionic molecules in the rat trachea within 15 minutes. Pediatr. Pulmonol. 1997;24:29–34. © 1997 Wiley‐Liss, Inc.
Bibliography:	ark:/67375/WNG-XV2NCD2H-P ArticleID:PPUL5 Viking's Children's Fund Cystic Fibrosis Foundation NIH - No. RO1 AI06931 istex:849F434F7B1A4D343C6FB3A617F38690D23BDF38 Minnesota Medical Foundation
ISSN:	8755-6863 1099-0496
DOI:	10.1002/(SICI)1099-0496(199707)24:1<29::AID-PPUL5>3.0.CO;2-E