Lung disease associated with α1-antitrypsin deficiency

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

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

α1-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 ofendogenous 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 lipopolyssacharide and tumor necrosis factor-a signaling.

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

Keywords

  • Apoptosis
  • COPD
  • Inflammation
  • Proteinase inhibitor
  • Serpin

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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