AJP - Lung Cellular and Molecular Physiology, Vol 266, Issue 6 593-L611, Copyright © 1994 by American Physiological Society
Cigarette smoking, emphysema, and damage to alpha 1-proteinase inhibitor
M. D. Evans and W. A. Pryor
Division of Chemical Pathology, Leicester University, United Kingdom.
The proteinase-antiproteinase theory for the pathogenesis of emphysema
proposes that the connective tissue destruction associated with emphysema
arises from excessive proteinase activity in the lower respiratory tract.
For this reason, the relative activities of neutrophil elastase and alpha
1-proteinase inhibitor (alpha 1-PI) are considered important. Most
emphysema is observed in smokers; therefore, alpha 1-PI has been studied as
a target for smoke-induced damage. Damage to alpha 1-PI in lung fluid could
occur by several mechanisms involving species delivered to the lung by
cigarette smoke and/or stimulated inflammatory cells. Oxidative damage to
alpha 1-PI has received particular attention, since both cigarette smoke
and inflammatory cells are rich sources of oxidants. In this article we
review almost two decades of research on mechanistic studies of damage to
alpha 1-PI by cigarette smoke and phagocytic cells in vitro, studies
emphasizing the importance of elastinolytic activity in the pathogenesis of
emphysema in vivo and studies of human lung lavage fluid to detect defects
in alpha 1-PI at the molecular and functional levels.
