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A Review of Alpha-1 Antitrypsin Binding Partners for Immune Regulation and Potential Therapeutic Application.
O'Brien, Michael E; Murray, Grace; Gogoi, Debananda; Yusuf, Azeez; McCarthy, Cormac; Wormald, Mark R; Casey, Michelle; Gabillard-Lefort, Claudie; McElvaney, Noel G; Reeves, Emer P.
  • O'Brien ME; Irish Centre for Genetic Lung Disease, Department of Medicine, RCSI University of Medicine and Health Sciences, Beaumont Hospital, D02 YN77 Dublin, Ireland.
  • Murray G; Irish Centre for Genetic Lung Disease, Department of Medicine, RCSI University of Medicine and Health Sciences, Beaumont Hospital, D02 YN77 Dublin, Ireland.
  • Gogoi D; Irish Centre for Genetic Lung Disease, Department of Medicine, RCSI University of Medicine and Health Sciences, Beaumont Hospital, D02 YN77 Dublin, Ireland.
  • Yusuf A; Irish Centre for Genetic Lung Disease, Department of Medicine, RCSI University of Medicine and Health Sciences, Beaumont Hospital, D02 YN77 Dublin, Ireland.
  • McCarthy C; Irish Centre for Genetic Lung Disease, Department of Medicine, RCSI University of Medicine and Health Sciences, Beaumont Hospital, D02 YN77 Dublin, Ireland.
  • Wormald MR; Department of Biochemistry, Oxford Glycobiology Institute, University of Oxford, Oxford OX1 3QU, UK.
  • Casey M; Irish Centre for Genetic Lung Disease, Department of Medicine, RCSI University of Medicine and Health Sciences, Beaumont Hospital, D02 YN77 Dublin, Ireland.
  • Gabillard-Lefort C; Irish Centre for Genetic Lung Disease, Department of Medicine, RCSI University of Medicine and Health Sciences, Beaumont Hospital, D02 YN77 Dublin, Ireland.
  • McElvaney NG; Irish Centre for Genetic Lung Disease, Department of Medicine, RCSI University of Medicine and Health Sciences, Beaumont Hospital, D02 YN77 Dublin, Ireland.
  • Reeves EP; Irish Centre for Genetic Lung Disease, Department of Medicine, RCSI University of Medicine and Health Sciences, Beaumont Hospital, D02 YN77 Dublin, Ireland.
Int J Mol Sci ; 23(5)2022 Feb 23.
Article in English | MEDLINE | ID: covidwho-1715404
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Apolipoproteins / Complement System Proteins / Alpha 1-Antitrypsin / Cytokines / Caspases Limits: Humans Language: English Year: 2022 Document Type: Article Affiliation country: Ijms23052441

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Apolipoproteins / Complement System Proteins / Alpha 1-Antitrypsin / Cytokines / Caspases Limits: Humans Language: English Year: 2022 Document Type: Article Affiliation country: Ijms23052441