PMID: 9441132Jun 1, 1997Paper

The proteinase-antiproteinase theory of emphysema: a speculative analysis of recent advances into the pathogenesis of emphysema

Respirology : Official Journal of the Asian Pacific Society of Respirology
K R KnightE D Janus

Abstract

This review concerns the reasons why only an estimated 10-15% of patients with alpha-1-antitrypsin (A1AT) deficiency develop the destructive lung disease known as emphysema. The arguments presented revolve around the proteinase-antiproteinase balance in the 'microenvironment' of the epithelial space of the lung. Attention is focused on the balance between destructive enzymes such as neutrophil elastase and protective proteins such as A1AT, secretory leucocyte proteinase inhibitor (SLPI), human elastase inhibitor (HEI) and elafin. When neutrophil elastase is already attached to the elastin fibres the smaller molecules SLPI and elafin appear to be better inhibitors of this enzyme than larger inhibitors such as A1AT and HEI. Furthermore, SLPI and elafin may provide the first line of defence against proteinase attack from neutrophil elastase. In trying to explain the variability in the clinical expression of A1AT-deficiency and the development of emphysema, the importance of changes to A1AT, SLPI and elafin molecules induced by smoking and/or oxygen free radicals has been considered. It is possible that emphysema only develops in patients who have SLPI/elafin deficiency as well as A1AT deficiency.

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Citations

Feb 17, 2009·Dermatology : International Journal for Clinical and Investigative Dermatology·B GrossS Janciauskiene
Dec 7, 2000·The New England Journal of Medicine·J A Lekstrom-Himes, J I Gallin
Nov 3, 2015·Clinica Chimica Acta; International Journal of Clinical Chemistry·Marni A NenkeDavid J Torpy
Apr 19, 2008·Reproductive Sciences·Laura L KleinJames L McManaman
Mar 19, 2002·Respirology : Official Journal of the Asian Pacific Society of Respirology·Jonathan G W BurdonEdward D Janus
Apr 11, 2003·Journal of Molecular Modeling·Hassan M BadawiKhalid S Al-Ghamdi
Sep 29, 2009·Journal of Clinical Pathology·N A Kalsheker
Mar 7, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·Chaobin Hu, David H Perlmutter
Feb 9, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·P CooperG Jarai
May 20, 2003·Respirology : Official Journal of the Asian Pacific Society of Respirology·Monna S AyadSue Brenton
Sep 24, 2002·Pharmacology & Therapeutics·Rommel S LanPeter J Henry

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