The role of neutrophil elastase in chronic inflammation.
Passively released or actively secreted elastase from neutrophils has been linked to the pathologic processes of a variety of inflammatory diseases, including idiopathic pulmonary fibrosis, rheumatoid arthritis, adult respiratory distress syndrome, and cystic fibrosis. The serine proteinase has a broad substrate specificity and may attack a number of host proteins outside of the neutrophil, including lung elastin and fibronectin. Such a proteolysis may change the normal surrounding tissue and the protein pattern of an inflammatory focus. Additionally, it acts as a potent secretagogue in minute amounts. The reason that neutrophil elastase is present in considerable concentrations outside of the neutrophil during chronic inflammation and that the major endogenous serine proteinase inhibitor for neutrophil elastase, alpha 1-proteinase inhibitor, is easily inactivated by proteolytic and oxidative attack is unclear. Released neutrophil elastase may also be involved in regulating chronic inflammation. In a feedback mechanism, neutrophil elastase inhibits neutrophil stimulation and concomitant elastase release by cleavage of immunoglobulins, complement components, and complement receptor type 1 on neutrophils. Besides a number of harmful effects of neutrophil elastase in inflammation, the latter mechanism, although considerably impairing phagocytosis, may be beneficial particularly in the light of persistent bacterial pathogens in the human lung affected by cystic fibrosis.
Department of General Hygiene and Environmental Hygiene, Hygiene-Institute, University of Tübingen, Germany.
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Döring
D000818:Animals; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000201:enzymology; D005089:Exocytosis; D006801:Humans; D007105:Immune Complex Diseases / Q000201:enzymology; D007249:Inflammation / Q000201:enzymology*; D019272:Leukocyte Elastase; D008171:Lung Diseases / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000502:physiology*; D010587:Phagocytosis
D010196:Pancreatic Elastase; D019272:Leukocyte Elastase