title: Alpha-1 Antitrypsin Deficiency: Beyond the Protease/Antiprotease Paradigm.
abstract: From the discovery that alpha-1 antitrypsin (AAT) was an effective inhibitor of neutrophil elastase originated the classic paradigm of protease/antiprotease imbalance, linking lung destruction to the unopposed effect of proteases in patients with the deficiency. Notwithstanding its importance as an antiprotease, it has become evident that alpha-1 antitrypsin has important antiinflammatory and immune-regulatory activities, which may be critically involved in lung destruction. We review here recent evidence showing that, indeed, an important adaptive immune reaction is present in lungs with AAT deficiency, similar to the one seen in severe chronic obstructive pulmonary disease with normal AAT. On the basis of recent evidence from epidemiological, clinical, and pathogenetic studies, it is likely time to move on from the original protease/antiprotease hypothesis for the production of emphysema toward a more complex paradigm, involving the antiinflammatory and immune modulating functions of AAT.
authors: 1 Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova, Padova, Italy; and.|2 Meakins-Christie Laboratories, Respiratory Division, McGill University, Montreal, Quebec, Canada.
authors: Manuel G
authors: MG
authors: Cosio
authors: 1 Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova, Padova, Italy; and.
authors: Erica
authors: E
authors: Bazzan
authors: 1 Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova, Padova, Italy; and.
authors: Chiara
authors: C
authors: Rigobello
authors: 1 Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova, Padova, Italy; and.
authors: Mariaenrica
authors: M
authors: Tinè
authors: 1 Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova, Padova, Italy; and.
authors: Graziella
authors: G
authors: Turato
authors: 1 Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova, Padova, Italy; and.
authors: Simonetta
authors: S
authors: Baraldo
authors: 1 Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova, Padova, Italy; and.
authors: Marina
authors: M
authors: Saetta
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D006801:Humans; D010447:Peptide Hydrolases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000378:metabolism; D019896:alpha 1-Antitrypsin Deficiency / Q000276:immunology* / Q000378:metabolism
chemical_list: D011480:Protease Inhibitors; D000515:alpha 1-Antitrypsin; D010447:Peptide Hydrolases
keywords: alpha-1 antitrypsin; emphysema; immunity; inflammation