Editing Alpha-1 antitrypsin (section)

{{Short description|Mammalian protein found in Homo sapiens}}
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'''Alpha-1 antitrypsin''' or '''α<sub>1</sub>-antitrypsin''' ('''A1AT''', '''α<sub>1</sub>AT''', '''A1A''', or '''AAT''') is a [[protein]] belonging to the [[serpin]] superfamily. It is encoded in humans by the ''SERPINA1'' [[gene]]. A [[protease inhibitor (biology)|protease inhibitor]], it is also known as '''alpha<sub>1</sub>–proteinase inhibitor''' ('''A1PI''') or '''alpha<sub>1</sub>-antiproteinase''' ('''A1AP''') because it inhibits various [[protease]]s (not just [[trypsin]]).<ref name=Gettins_2002>{{cite journal | vauthors = Gettins PG | title = Serpin structure, mechanism, and function | journal = Chemical Reviews | volume = 102 | issue = 12 | pages = 4751–804 | date = December 2002 | pmid = 12475206 | doi = 10.1021/cr010170 }}</ref>  As a type of [[enzyme inhibitor]], it protects [[tissue (biology)|tissues]] from [[enzyme]]s of [[inflammation|inflammatory]] cells, especially [[neutrophil elastase]].

When the [[blood]] contains inadequate or defective A1AT (as in [[alpha 1-antitrypsin deficiency|alpha-1 antitrypsin deficiency]]), neutrophil elastase can excessively break down [[elastin]], leading to the loss of [[elasticity (physics)|elasticity]] in the [[lung]]s. This results in [[pulmonology|respiratory issues]], such as [[chronic obstructive pulmonary disease]], in adults. Normally, A1AT is produced in the [[liver]] and enters the [[circulatory system#Systemic circulation|systemic circulation]]. However, defective A1AT may accumulate in the liver, potentially causing [[cirrhosis]] in both adults and [[pediatrics|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.<ref>{{cite journal | vauthors = Guttman O, Baranovski BM, Schuster R, Kaner Z, Freixo-Lima GS, Bahar N, Mizrahi MI, Brami I, Ochayon DE, Lewis EC | title = Acute-phase protein α1-anti-trypsin: diverting injurious innate and adaptive immune responses from non-authentic threats | journal = Clinical & Experimental Immunology | volume = 179 | issue = 2 | pages = 161–172 | date = February 2015 | pmid = 25351931 | pmc = 4298394 | doi = 10.1111/cei.12476 }}</ref> Besides liver cells, A1PI is also produced in bone marrow, lymphoid tissue, and the Paneth cells of the gut.<ref>{{cite journal | vauthors = Winkler IG, Hendy J, Coughlin P, Horvath A, Lévesque JP | title = Serine protease inhibitors serpina1 and serpina3 are down-regulated in bone marrow during hematopoietic progenitor mobilization | journal = The Journal of Experimental Medicine | volume = 201 | issue = 7 | pages = 1077–88 | date = April 2005 | pmid = 15795238 | pmc = 2213124 | doi = 10.1084/jem.20042299 }}</ref>

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.<ref>{{cite journal | vauthors = Richler R, Forssmann W, Henschler R | title = Current developments in mobilization of hematopoietic stem and progenitor cells and their interaction with niches in bone marrow | journal = Transfus Med Hemother | volume = 44 | issue = 3 | pages = 151–164 | date = June 2017 | pmid = 28626366 | pmc = 5473067 | doi = 10.1159/000477262 }}</ref>
A1AT is both [[protease inhibitor (biology)|an endogenous protease inhibitor]] and [[protease inhibitor (pharmacology)|an exogenous one used as medication]]. The [[pharmaceutical drug|pharmaceutical]] form is purified from [[blood donation|human donor blood]] and is sold under the [[drug nomenclature#Nonproprietary (generic) names|nonproprietary name]] alpha<sub>1</sub>–proteinase inhibitor (human) and under various trade names (including <!-- alphabetical order --> Aralast NP, Glassia, Prolastin, Prolastin-C, and Zemaira). [[Recombinant DNA|Recombinant]] versions are also available but are currently used in [[medical research]] more than as medication.