Lung disease associated with alpha1-antitrypsin deficiency.

Rubin M. Tuder, Sabina M. Janciauskiene, Irina Petrache

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

α(1)-Antitrypsin (A1AT) is a polyvalent, acute-phase reactant with an extensive range of biological functions that go beyond those usually linked to its antiprotease (serpin) activities. Genetic mutations cause a systemic deficiency of A1AT, leading to liver and pulmonary diseases, including emphysema and chronic bronchitis. The pathogenesis of emphysema, which involves the destruction of small airway structures and alveolar units, is triggered by cigarette smoke and pollutants. The tissue damage caused by these agents is further potentiated by the mutual interactions between apoptosis, oxidative stress, and protease/antiprotease imbalance. These processes lead to the activation of endogenous mediators of tissue destruction, including the lipid ceramide, extracellular matrix proteins, and abnormal inflammatory cell signaling. In this review, we propose that A1AT has a range of actions that are not restricted to protease inhibition but rather extend to mitigate a range of these pathological processes involved in the development of emphysema. We discuss the evidence indicating that A1AT blocks apoptosis by binding and inhibiting active caspase-3 and modulates a broad range of inflammatory responses induced by neutrophils and by lipopolysaccharide and tumor necrosis factor-α signaling.

Original languageEnglish (US)
Pages (from-to)381-386
Number of pages6
JournalProceedings of the American Thoracic Society
Volume7
Issue number6
StatePublished - Nov 2010

Fingerprint

Emphysema
Lung Diseases
Protease Inhibitors
Peptide Hydrolases
Apoptosis
Serpins
Acute-Phase Proteins
Ceramides
Extracellular Matrix Proteins
Chronic Bronchitis
Pathologic Processes
Smoke
Tobacco Products
Caspase 3
Lipopolysaccharides
Liver Diseases
Oxidative Stress
Neutrophils
Tumor Necrosis Factor-alpha
Lipids

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Lung disease associated with alpha1-antitrypsin deficiency. / Tuder, Rubin M.; Janciauskiene, Sabina M.; Petrache, Irina.

In: Proceedings of the American Thoracic Society, Vol. 7, No. 6, 11.2010, p. 381-386.

Research output: Contribution to journalArticle

Tuder, Rubin M. ; Janciauskiene, Sabina M. ; Petrache, Irina. / Lung disease associated with alpha1-antitrypsin deficiency. In: Proceedings of the American Thoracic Society. 2010 ; Vol. 7, No. 6. pp. 381-386.
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