Role of neutrophils and α1-antitrypsin in coal- and silica-induced connective tissue breakdown
| Autor: | Changshi Xie, Andrew Churg, D. V. Devine, Katalin Zay, Joanne L. Wright, S. Loo |
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| Rok vydání: | 1999 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine Pathology medicine.medical_specialty Time Factors Neutrophils Physiology Neutrophile Connective tissue Desmosine Rats Sprague-Dawley Pathogenesis Leukocyte Count Hydroxyproline chemistry.chemical_compound Physiology (medical) medicine Animals Respiratory system Connective Tissue Diseases Lung Metalloproteinase Pancreatic Elastase Chemistry Immune Sera Macrophages Metalloendopeptidases Cell Biology Silicon Dioxide Rats Coal medicine.anatomical_structure alpha 1-Antitrypsin Bronchoalveolar Lavage Fluid |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 276:L269-L279 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.1999.276.2.l269 |
| Popis: | Mineral dusts produce emphysema, and administration of dust to rats results in the rapid appearance of desmosine and hydroxyproline in lavage fluid, confirming that dusts directly induce connective tissue breakdown. To examine the role of neutrophils and α1-antitrypsin (α1-AT) in this process, we instilled silica or coal into normal rats or rats that had been pretreated with antiserum against neutrophils. One day after dust exposure, lavage fluid neutrophils and desmosine and hydroxyproline levels were all elevated; treatment with antiserum against neutrophils reduced neutrophils by 75%, desmosine by 40–50%, and hydroxyproline by 25%. By 7 days, lavage fluid neutrophils and desmosine level had decreased, whereas macrophages and hydroxyproline level had increased. By ELISA analysis, lavage fluid α1-AT levels were increased four- to eightfold at both times. On Western blot, some of the α1-AT appeared as degraded fragments, and by HPLC analysis, 5–10% of the methionine residues were oxidized. At both times, lavage fluid exhibited considerably elevated serine elastase inhibitory capacity and also showed elevations in metalloelastase activity. We conclude that, in this model, connective tissue breakdown is initially driven largely by neutrophil-derived proteases and that markedly elevated levels of functional α1-AT do not prevent breakdown, thus providing in vivo support for the concept of quantum proteolysis proposed by Liou and Campbell (T. G. Liou and E. J. Campbell. Biochemistry 34: 16171–16177, 1995). Macrophage-derived proteases may be of increasing importance over time, especially in coal-treated animals. |
| Databáze: | OpenAIRE |
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