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© 2006 The American Thoracic Society
doi: 10.1513/pats.200603-054MS
State of the Art. Cellular and Molecular Mechanisms of Alveolar Destruction in Emphysema
An Evolutionary Perspective
Division of Cardiopulmonary Pathology, Department of Pathology, and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; and University of Texas M.D. Anderson Cancer Center, Houston, Texas
Correspondence and requests for reprints should be addressed to Rubin M. Tuder, M.D., Division of Cardiopulmonary Pathology, Department of Pathology, Ross Research Building, Ross 519, 720 Rutland Avenue, Baltimore, MD 21205. E-mail: rtuder{at}jhmi.edu
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.
Key Words: aging • apoptosis • emphysema • inflammation • oxidative stress
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