Role of connective tissue proteases in the pathogenesis of chronic inflammatory lung disease.

J. E. Gadek, G. A. Fells, R. L. Zimmerman, Ronald Crystal

Research output: Contribution to journalReview article

35 Citations (Scopus)

Abstract

The normal structure and function of the human lung is dependent on the maintenance of the connective tissue matrix. These structural macromolecules provide the template for normal parenchymal cell architecture on which efficient gas exchange depends. In addition, the organization and amount of this extracellular matrix accounts for much of the mechanical behavior of the lung parenchyma during the respiratory cycle. The preservation of this intricate connective tissue scaffold depends on the lung's capacity to prevent enzymatic disruption of the component matrix proteins. Specifically, the integrity of the normal connective tissue skeleton of the lung is determined by the maintenance of a balance between proteases capable of cleaving these structural elements and the specific protease inhibitors. The normal extracellular matrix is preserved when the local concentrations of protease inhibitors prohibits expression of active connective tissue proteases within the lung parenchyma. Conversely, the disruption of lung structure during the course of acute and chronic inflammatory diseases of the lung is often associated with an imbalance of protease-antiprotease activity. The consequence is the expression of unimpeded proteolytic attack on the connective tissue matrix of the lung. In this context, the nature of the pulmonary lesion and its physiologic consequences, reflect the specificity of the expressed proteases for the individual connective tissue components. Experimental evidence suggests that the differential expression of collagenase and elastase, prototypes of connective tissue proteases, may determine whether the pathologic outcome is fibrosis (e.g., idiopathic pulmonary fibrosis) or destruction (e.g., emphysema) of the alveolar structures.

Original languageEnglish
Pages (from-to)297-306
Number of pages10
JournalEnvironmental Health Perspectives
Volume55
Publication statusPublished - 1 Apr 1984
Externally publishedYes

Fingerprint

Pulmonary diseases
Connective Tissue
Lung Diseases
Peptide Hydrolases
Tissue
Lung
Protease Inhibitors
matrix
inhibitor
Tissue Scaffolds
Extracellular Matrix
Pancreatic Elastase
Maintenance
Collagenases
Macromolecules
Lung Volume Measurements
Idiopathic Pulmonary Fibrosis
tissue
gas exchange
lesion

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Public Health, Environmental and Occupational Health

Cite this

Role of connective tissue proteases in the pathogenesis of chronic inflammatory lung disease. / Gadek, J. E.; Fells, G. A.; Zimmerman, R. L.; Crystal, Ronald.

In: Environmental Health Perspectives, Vol. 55, 01.04.1984, p. 297-306.

Research output: Contribution to journalReview article

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