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Antielastases of the human alveolar structures. Implications for the protease-antiprotease theory of emphysema.

Abstract
The current concepts of the pathogenesis of emphysema hold that progressive, chronic destruction of the alveolar structures occurs because there was in imbalance between the proteases and antiproteases in the lower respiratory tract. In this context, proteases, particularly neutrophil elastase, work unimpeded to destroy the alveolar structures. This concept has evolved from consideration of patients with alpha 1-antitrypsin deficiency, who have decreased levels of serum alpha 1-antitrypsin and who have progressive panacinar emphysema. To directly assess the antiprotease side of this equation, the lower respiratory tract of non-smoking individuals with normal serum antiproteases and individuals with PiZ homozygous alpha 1-antitrypsin deficiency underwent bronchoalveolar lavage to evaluate the antiprotease screen of their lower respiratory tract. These studies demonstrated that: (a) alpha 1-antitrypsin is the major antielastase of the normal human lower respiratory tract; (b) alpha 2-macroglobulin, a large serum antielastase, and the bronchial mucous inhibitor, an antielastase of the central airways, do not contribute to the antielastase protection of the human alveolar structures; (c) individuals with PiZ alpha 1-antitrypsin deficiency have little or no alpha 1-antitrypsin in their lower respiratory tract and have no alternative antiprotease protection against neutrophil elastase; and (d) the lack of antiprotease protection of the lower respiratory tract of PiZ individuals is a chronic process, suggesting their vulnerability to neutrophil elastase is always present.
AuthorsJ E Gadek, G A Fells, R L Zimmerman, S I Rennard, R G Crystal
JournalThe Journal of clinical investigation (J Clin Invest) Vol. 68 Issue 4 Pg. 889-98 (Oct 1981) ISSN: 0021-9738 [Print] United States
PMID6169740 (Publication Type: Journal Article)
Chemical References
  • Protease Inhibitors
  • alpha-Macroglobulins
  • Pancreatic Elastase
Topics
  • Bronchi (enzymology)
  • Heterozygote
  • Homozygote
  • Humans
  • Lung (enzymology)
  • Neutrophils (enzymology)
  • Pancreatic Elastase (antagonists & inhibitors)
  • Protease Inhibitors (metabolism)
  • Pulmonary Emphysema (enzymology, genetics)
  • alpha 1-Antitrypsin Deficiency
  • alpha-Macroglobulins (metabolism)

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