Abstract
Alpha-1 antitrypsin (AAT) is the canonical serine protease inhibitor of neutrophil-derived proteases and can modulate innate immune mechanisms through its anti-inflammatory activities mediated by a broad spectrum of protein, cytokine, and cell surface interactions. AAT contains a reactive methionine residue that is critical for its protease-specific binding capacity, whereby AAT entraps the protease on cleavage of its reactive centre loop, neutralises its activity by key changes in its tertiary structure, and permits removal of the AAT-protease complex from the circulation. Recently, however, the immunomodulatory role of AAT has come increasingly to the fore with several prominent studies focused on lipid or protein-protein interactions that are predominantly mediated through electrostatic, glycan, or hydrophobic potential binding sites. The aim of this review was to investigate the spectrum of AAT molecular interactions, with newer studies supporting a potential therapeutic paradigm for AAT augmentation therapy in disorders in which a chronic immune response is strongly linked.
Highlights
We provide an overview of Alpha-1 antitrypsin (AAT) and the interaction between this antiprotease and its biological environment in order to better understand the function of AAT in health and disease and the emerging therapeutic role of AAT augmentation therapy beyond deficiency states
Cell signalling mechanisms leading to downregulation of AAT production are underexplored, with one in vitro study leading to downregulation of AAT production are underexplored, with one in vitro study indicating the ability of AAT itself to downregulate SERPINA1 mRNA expression in both indicating the ability of AAT itself to downregulate SERPINA1 mRNA expression in both hepatocytes and peripheral blood mononuclear cells [46]
Alpha-1 antitrypsin (AAT) is the canonical serine protease inhibitor that has been the subject of extensive study
Summary
O’Brien 1 , Grace Murray 1 , Debananda Gogoi 1 , Azeez Yusuf 1 , Cormac McCarthy 1 , Mark R. Wormald 2 , Michelle Casey 1 , Claudie Gabillard-Lefort 1 , Noel G.
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