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

J. E. Gadek, G. A. Fells, R. L. Zimmerman, S. I. Rennard, R. G. Crystal

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Abstract

The current concepts of the pathogenesis of emphysema hold that progressive, chronic destruction of the alveolar structures occurs because there is an 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 α1-antitrypsin deficiency, who have decreased levels of serum α1-antitrypsin and who have progressive panacinar emphysema. To directly assess the antiprotease side of this equation, the lower respiratory tract of nonsmoking individuals with serum antiproteases and individuals with PiZ homozygous α1-antitrypsin deficiency underwent bronchoalveolar lavage to evaluate the antiprotease screen of their lower respiratory tract. These studies demonstrated that: (a) α1-antitrypsin is the major antielastase of the normal human lower respiratory tract; (b) α2-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 α1-antitrypson deficiency have little or no α1-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.

Original languageEnglish (US)
Pages (from-to)889-898
Number of pages10
JournalUnknown Journal
Volume68
Issue number4
DOIs
StatePublished - Jan 1 1981

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ASJC Scopus subject areas

  • Medicine(all)

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Gadek, J. E., Fells, G. A., Zimmerman, R. L., Rennard, S. I., & Crystal, R. G. (1981). Antielastases of the human alveolar structures. Implications for the protease-antiprotease theory of emphysema. Unknown Journal, 68(4), 889-898. https://doi.org/10.1172/JCI110344