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

Abstract

1-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, 1-antitrypsin is thought to play an important role in limiting host tissue injury at sites of inflammation. The clinical importance of 1-antitrypsin is highlighted in individuals with inherited 1-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 1-antitrypsin may also exhibit biological activity independent of its protease inhibitor function. Thus, conformationally modified and degraded forms of 1-antitrypsin, which lack antiprotease activity, demonstrate specific biological effects in vitro and in vivo and highlight the potentially broader modulatory role of 1-antitrypsin in inflammatory diseases.In this review we discuss the biological properties of 1-antitrypsin and its role in chronic obstructive pulmonary diseases. A more comprehensive understanding of the biology of native 1-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 1-antitrypsin.

Inflammatory markers in chronic obstructive pulmonary disease patients with different α1 antitrypsin genotypes

“…It has been recently shown that AAT regulates many physiological and pathological processes, which may significantly influence the disease process, including cell-mediated immunity, apoptosis, tumor cell growth, and many others [15]. α1 Antitrypsin has even been shown to regulate expression of CD14, a receptor for lipopolysaccharides (LPS), in human monocytes in vitro [16].…”

α1-Antitrypsin level in patients with spontaneous pneumothorax

“…On the one hand, elevated serum AAT levels can reflect a beneficial shift in the protease-antiprotease balance, the cornerstone of the pathophysiological pathway mediating the effect of severe AAT deficiency on lung tissue [3]. On the other hand, elevated serum AAT can also reflect low-grade inflammatory processes in the lungs [2], which are considered a risk factor for alveoli damage. Our study had some limitations: the level of systemic inflammatory markers was not measured, and this could have an impact on our results.…”

“…a1-Antitrypsin (AAT) deficiency is a genetic disorder that predisposes individuals to the development of liver and lung disease [1,2].…”

Ethnic differences in alpha-1 antitrypsin deficiency in the United States of America

“…Although its primary function is to inhibit neutrophil elastase, AAT has a broad spectrum of anti-inflammatory and connective tissue repair functions [Janciauskiene et al 2007]. AAT gene is subject to mutations in the five-exon gene at q31-32.1 on the long arm of chromosome 14.…”