New Insights into the Biology of 1-Antitrypsin and its Role in Chronic Obstructive Pulmonary Disease

α1-antitrypsin, an acute phase protein, is the prototypic member of the serpin super family and a major inhibitor of serine proteases. As an acute phase protein, α1-antitrypsin is thought to play an important role in limiting host tissue injury at sites of inflammation. The clinical importance of α1-antitrypsin is highlighted in individuals with inherited α1- antitrypsin deficiency who exhibit an increased susceptibility to develop chronic inflammatory conditions including chronic obstructive pulmonary disease, systemic vasculitis and necrotizing panniculitis. There is now an increasing evidence that α1-antitrypsin may also exhibit biological activity independent of its protease inhibitor function. Thus, conformationally modified and degraded forms of α1-antitrypsin, which lack antiprotease activity, demonstrate specific biological effects in vitro and in vivo and highlight the potentially broader modulatory role of α1-antitrypsin in inflammatory diseases. In this review we discuss the biological properties of α1-antitrypsin and its role in chronic obstructive pulmonary diseases. A more comprehensive understanding of the biology of native α1-antitrypsin and its modified forms may have a significant impact on our understanding and ultimately treatment of disease pathologies arising from both natural point mutations and from post-synthetically modified byproducts of α1-antitrypsin.