The α₁-antitrypsin gene and emphysema

α₁-Antitrypsin (α₁-AT) is the major endogenous inhibitor of neutrophil elastase. Individuals with α₁-AT deficiency are susceptible to premature development of emphysema. Thus a greater understanding of this serine proteinase inhibitor (serpin) has been a major objective of research on the pathogenesis of emphysema. In this article, we review recent literature on the α₁-AT gene and its relationship to other members of the serpin supergene family, particularly as it pertains to the function of α₁-AT. We also discuss the current literature on biosynthesis of α₁-AT and how its synthesis may be tightly regulated by the net balance of neutrophil elastase and α₁-AT at sites of inflammation/tissue injury. The net functional activity of α₁-AT in complex biological fluids is also affected by interaction with other enzymes, inhibitors, matrix proteins, and endogenous oxidants. Finally, we discuss the pathogenesis, clinical manifestations, and treatment of injury to the lung associated with deficiency variants of the α₁-AT gene.