Role of connective tissue proteases in the pathogenesis of chronic inflammatory lung disease.
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.
D000818:Animals; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D003238:Connective Tissue / Q000201:enzymology*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000201:enzymology*; D003012:Microbial Collagenase / Q000378:metabolism; D010196:Pancreatic Elastase / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D011014:Pneumonia / Q000201:enzymology*; D011480:Protease Inhibitors / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000033:anatomy & histology
D006023:Glycoproteins; D011480:Protease Inhibitors; D011509:Proteoglycans; D003094:Collagen; D010447:Peptide Hydrolases; D010196:Pancreatic Elastase; D003012:Microbial Collagenase