The multiple facets of alpha-1-antitrypsin - PubMed (original) (raw)

The multiple facets of alpha-1-antitrypsin

Robert A Stockley. Ann Transl Med. 2015 Jun.

Abstract

Alpha-1-antitrypsin (AAT) is recognised as a potent inhibitor of serine proteinases. Genetic deficiency is associated with several neutrophilic diseases including severe emphysema. This is believed to reflect the loss of inhibition of neutrophilic serine proteinases that then result in local tissue damage (the proteinase/antiprotease hypothesis). In recent years the role of AAT in the control of inflammatory and immunological processes has become identified. Although in some instances this may reflect its ability to control pro-inflammatory effects of serine proteinases it has also become recognised that it has non proteolytic mediated functions. This poly functional role is starting to become recognised offering a possibility of its use as a therapeutic agent in many clinical disease areas. The current review explores both the traditional and non-traditional function of AAT through published literature.

Keywords: Alpha-1-antitrypsin (AAT); immunity; inflammation.

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Figures

Figure 1

Figure 1

AAT in the airways acts as both an anti-oxidant (A) and anti-protease (B) thereby preventing the pro-inflammatory activity of both on local production of cytokines and chemoattractants. In addition AAT blocks the autocrine activity of TNF also impairing cytokine and adhesion molecule up regulation (C) AAT also down regulates Neutrophil chemotactic response (D) leading to less tissue damage by migrating cells (E). AAT, alpha-1-antitrypsin.

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