Cellular and molecular mechanisms of alveolar destruction in emphysema

An evolutionary perspective

Rubin M. Tuder, Toshinori Yoshida, Wadih Arap, Renata Pasqualini, Irina Petrache

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

Emphysema consists of a unique pattern of alveolar destruction, resulting in marked airspace enlargement with reduction of alveolar capillary exchange area. Classical concepts of the pathogenesis of emphysema have relied on the paradigm set by the inflammation and protease/antiprotease imbalance. We propose herein that cigarette smoke constitutes an environmental hazard that causes alveolar destruction by the interaction of apoptosis, oxidative stress, and protease/antiprotease imbalance. We draw a parallel between organismal aging, organ structural maintenance, and the damage resulting from chronic cigarette smoke inhalation. The stochastic interaction between environmental hazards and the effort of an organism or a particular organ to fend off these hazards results in the accumulation of cellular damage and features characteristic of aging. Inflammation follows as the result of the multiplication of injuries. We highlight the importance of understanding the biology of the interaction of alveolar cells in homeostasis and in alveolar destruction, and the potential role of novel processes related to senescence and stress response. An evolutionary perspective of emphysema that incorporates mechanisms related to aging may lead to important advances in the understanding and therapeutic targeting of chronic obstructive pulmonary disease.

Original languageEnglish (US)
Pages (from-to)503-510
Number of pages8
JournalProceedings of the American Thoracic Society
Volume3
Issue number6
DOIs
StatePublished - 2006
Externally publishedYes

Fingerprint

Emphysema
Protease Inhibitors
Smoke
Tobacco Products
Peptide Hydrolases
Inflammation
Alveolar Epithelial Cells
Chronic Obstructive Pulmonary Disease
Inhalation
Oxidative Stress
Homeostasis
Maintenance
Apoptosis
Wounds and Injuries
Therapeutics

Keywords

  • Aging
  • Apoptosis
  • Emphysema
  • Inflammation
  • Oxidative stress

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology
  • Cell Biology

Cite this

Cellular and molecular mechanisms of alveolar destruction in emphysema : An evolutionary perspective. / Tuder, Rubin M.; Yoshida, Toshinori; Arap, Wadih; Pasqualini, Renata; Petrache, Irina.

In: Proceedings of the American Thoracic Society, Vol. 3, No. 6, 2006, p. 503-510.

Research output: Contribution to journalArticle

Tuder, Rubin M. ; Yoshida, Toshinori ; Arap, Wadih ; Pasqualini, Renata ; Petrache, Irina. / Cellular and molecular mechanisms of alveolar destruction in emphysema : An evolutionary perspective. In: Proceedings of the American Thoracic Society. 2006 ; Vol. 3, No. 6. pp. 503-510.
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