Back ألفا 1-أنتيتريبسين Arabic آلفا یک آنتیتریپسین AZB Alfa 1-antitripsin BS Alfa-1-antitripsina Catalan SERPINA1 Welsh Α-1-Antitrypsin German Alfa 1-antitripsina Spanish آلفا یک آنتیتریپسین Persian Antitrypsiini Finnish Alpha-1-antitrypsine French
Alpha-1 antitrypsin or α1-antitrypsin (A1AT, α1AT, A1A, or AAT) is a protein belonging to the serpin superfamily. It is encoded in humans by the SERPINA1 gene. A protease inhibitor, it is also known as alpha1–proteinase inhibitor (A1PI) or alpha1-antiproteinase (A1AP) because it inhibits various proteases (not just trypsin).[5] As a type of enzyme inhibitor, it protects tissues from enzymes of inflammatory cells, especially neutrophil elastase.
When the blood contains inadequate or defective A1AT (as in alpha-1 antitrypsin deficiency), neutrophil elastase can excessively break down elastin, leading to the loss of elasticity in the lungs. This results in respiratory issues, such as chronic obstructive pulmonary disease, in adults. Normally, A1AT is produced in the liver and enters the systemic circulation. However, defective A1AT may accumulate in the liver, potentially causing cirrhosis in both adults and children.
A1AT not only binds to neutrophil elastase from inflammatory cells but also to elastase on the cell surface. In this latter role, elastase acts as a signaling molecule for cell movement, rather than as an enzyme.[6] Besides liver cells, A1PI is also produced in bone marrow, lymphoid tissue, and the Paneth cells of the gut.[7]
Inactivation of A1AT by other enzymes during inflammation or infection can halt T cell migration precisely at the site of the pathological insult. This suggests that α1PI plays a key role in lymphocyte movement and immune surveillance, particularly in response to infection.[8] A1AT is both an endogenous protease inhibitor and an exogenous one used as medication. The pharmaceutical form is purified from human donor blood and is sold under the nonproprietary name alpha1–proteinase inhibitor (human) and under various trade names (including Aralast NP, Glassia, Prolastin, Prolastin-C, and Zemaira). Recombinant versions are also available but are currently used in medical research more than as medication.
- ^ a b c ENSG00000277377 GRCh38: Ensembl release 89: ENSG00000197249, ENSG00000277377 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000071177 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Gettins PG (December 2002). "Serpin structure, mechanism, and function". Chemical Reviews. 102 (12): 4751–804. doi:10.1021/cr010170. PMID 12475206.
- ^ Guttman O, Baranovski BM, Schuster R, Kaner Z, Freixo-Lima GS, Bahar N, et al. (February 2015). "Acute-phase protein α1-anti-trypsin: diverting injurious innate and adaptive immune responses from non-authentic threats". Clinical & Experimental Immunology. 179 (2): 161–172. doi:10.1111/cei.12476. PMC 4298394. PMID 25351931.
- ^ Winkler IG, Hendy J, Coughlin P, Horvath A, Lévesque JP (April 2005). "Serine protease inhibitors serpina1 and serpina3 are down-regulated in bone marrow during hematopoietic progenitor mobilization". The Journal of Experimental Medicine. 201 (7): 1077–88. doi:10.1084/jem.20042299. PMC 2213124. PMID 15795238.
- ^ Richler R, Forssmann W, Henschler R (June 2017). "Current developments in mobilization of hematopoietic stem and progenitor cells and their interaction with niches in bone marrow". Transfus Med Hemother. 44 (3): 151–164. doi:10.1159/000477262. PMC 5473067. PMID 28626366.