State of the art. Cellular and molecular mechanisms of alveolar destruction in emphysema: an evolutionary perspective.

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.

[1]  César A. Hidalgo,et al.  Scale-free networks , 2008, Scholarpedia.

[2]  T. Flotte,et al.  A novel antiapoptotic role for alpha1-antitrypsin in the prevention of pulmonary emphysema. , 2006, American journal of respiratory and critical care medicine.

[3]  D. Postma,et al.  Effect of 1-year smoking cessation on airway inflammation in COPD and asymptomatic smokers , 2005, European Respiratory Journal.

[4]  John D. Mitchell,et al.  Oligoclonal CD4+ T cells in the lungs of patients with severe emphysema. , 2005, American journal of respiratory and critical care medicine.

[5]  R. Flavell,et al.  Role of Cathepsin S-Dependent Epithelial Cell Apoptosis in IFN-γ-Induced Alveolar Remodeling and Pulmonary Emphysema1 , 2005, The Journal of Immunology.

[6]  I. Adcock,et al.  Decreased histone deacetylase activity in chronic obstructive pulmonary disease. , 2005, The New England journal of medicine.

[7]  D. Hicklin,et al.  Vascular endothelial growth factor receptor 2 blockade disrupts postnatal lung development. , 2005, American journal of respiratory cell and molecular biology.

[8]  I. Petrache,et al.  Ceramide upregulation causes pulmonary cell apoptosis and emphysema-like disease in mice , 2005, Nature Medicine.

[9]  N. Voelkel,et al.  An animal model of autoimmune emphysema. , 2005, American journal of respiratory and critical care medicine.

[10]  Robert S. Balaban,et al.  Mitochondria, Oxidants, and Aging , 2005, Cell.

[11]  T. Kirkwood,et al.  Understanding the Odd Science of Aging , 2005, Cell.

[12]  J. Campisi.  Senescent Cells, Tumor Suppression, and Organismal Aging: Good Citizens, Bad Neighbors , 2005, Cell.

[13]  Frederick W. Alt,et al.  DNA Repair, Genome Stability, and Aging , 2005, Cell.

[14]  S. Korn,et al.  Characterization of the interstitial lung and peripheral blood T cell receptor repertoire in cigarette smokers. , 2005, American journal of respiratory cell and molecular biology.

[15]  S. Shapiro,et al.  COPD unwound. , 2005, The New England journal of medicine.

[16]  P. Henson,et al.  Autoimmunity and apoptosis: refusing to go quietly , 2005, Nature Medicine.

[17]  J. Hogg.  Peripheral lung remodelling in asthma and chronic obstructive pulmonary disease , 2004, European Respiratory Journal.

[18]  Irina Petrache,et al.  Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke-induced emphysema in mice. , 2004, The Journal of clinical investigation.

[19]  N. Sharpless,et al.  Ink4a/Arf expression is a biomarker of aging. , 2004, The Journal of clinical investigation.

[20]  H. Rossiter,et al.  Lung-targeted VEGF inactivation leads to an emphysema phenotype in mice. , 2004, Journal of applied physiology.

[21]  D. Corry,et al.  An Immune Basis for Lung Parenchymal Destruction in Chronic Obstructive Pulmonary Disease and Emphysema , 2004, PLoS medicine.

[22]  Eileen M. Crimmins,et al.  Inflammatory Exposure and Historical Changes in Human Life-Spans , 2004, Science.

[23]  T. Tsuji,et al.  Cigarette smoke induces senescence in alveolar epithelial cells. , 2004, American journal of respiratory cell and molecular biology.

[24]  Wadih Arap,et al.  Reversal of obesity by targeted ablation of adipose tissue , 2004, Nature Medicine.

[25]  K. Aoshiba,et al.  Increased levels of cell death and proliferation in alveolar wall cells in patients with pulmonary emphysema. , 2004, Chest.

[26]  F. Chu,et al.  Human alveolar wall fibroblasts directly link epithelial type 2 cells to capillary endothelium. , 2003, American journal of respiratory and critical care medicine.

[27]  Y. Hannun,et al.  Ceramide, stress, and a "LAG" in aging. , 2003, Science of aging knowledge environment : SAGE KE.

[28]  M. Cosio,et al.  Hypothesis: Does COPD have an autoimmune component? , 2003, Thorax.

[29]  N. Ferrara,et al.  The biology of VEGF and its receptors , 2003, Nature Medicine.

[30]  N. Voelkel,et al.  Apoptosis and emphysema: the missing link. , 2003, American journal of respiratory cell and molecular biology.

[31]  K. Hirata,et al.  Possible effects of vascular endothelial growth factor in the pathogenesis of chronic obstructive pulmonary disease. , 2003, The American journal of medicine.

[32]  J. Bhattacharya,et al.  Mechano-oxidative coupling by mitochondria induces proinflammatory responses in lung venular capillaries. , 2003, The Journal of clinical investigation.

[33]  N. Voelkel,et al.  Oxidative stress and apoptosis interact and cause emphysema due to vascular endothelial growth factor receptor blockade. , 2003, American journal of respiratory cell and molecular biology.

[34]  Kim-Anh Do,et al.  Steps toward mapping the human vasculature by phage display , 2002, Nature Medicine.

[35]  W. MacNee,et al.  4-Hydroxy-2-nonenal, a specific lipid peroxidation product, is elevated in lungs of patients with chronic obstructive pulmonary disease. , 2002, American journal of respiratory and critical care medicine.

[36]  Till Acker,et al.  Loss of HIF-2α and inhibition of VEGF impair fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice , 2002, Nature Medicine.

[37]  I. Komuro,et al.  Endothelial Cell Senescence in Human Atherosclerosis: Role of Telomere in Endothelial Dysfunction , 2002, Circulation.

[38]  Dena Leshkowitz,et al.  Identification of a Novel Hypoxia-Inducible Factor 1-Responsive Gene, RTP801, Involved in Apoptosis , 2002, Molecular and Cellular Biology.

[39]  P. Carmeliet,et al.  Loss of HIF-2α and inhibition of VEGF impair fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice , 2002, Nature Medicine.

[40]  W. MacNee,et al.  Oxidants/antioxidants and chronic obstructive pulmonary disease: pathogenesis to therapy. , 2008, Novartis Foundation symposium.

[41]  S. Abman.  Bronchopulmonary dysplasia: "a vascular hypothesis". , 2001, American journal of respiratory and critical care medicine.

[42]  D A Lynch,et al.  Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema. , 2001, American journal of respiratory and critical care medicine.

[43]  K. A. Noren,et al.  Construction of high-complexity combinatorial phage display peptide libraries. , 2001, Methods.

[44]  W. Kuebler,et al.  A novel signaling mechanism between gas and blood compartments of the lung , 2000, The Journal of clinical investigation.

[45]  M. Gaxiola,et al.  Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD. , 2000, Chest.

[46]  J. Shannon,et al.  Tissue interactions mediate early events in pulmonary vasculogenesis , 2000, Developmental dynamics : an official publication of the American Association of Anatomists.

[47]  W. MacNee,et al.  Oxidants and antioxidants as therapeutic targets in chronic obstructive pulmonary disease. , 1999, American journal of respiratory and critical care medicine.

[48]  Erkki Ruoslahti,et al.  Anti-cancer activity of targeted pro-apoptotic peptides , 1999, Nature Medicine.

[49]  M Aguet,et al.  VEGF is required for growth and survival in neonatal mice. , 1999, Development.

[50]  J. Janssens,et al.  Physiological changes in respiratory function associated with ageing. , 1999, The European respiratory journal.

[51]  W. MacNee,et al.  Systemic oxidative stress in asthma, COPD, and smokers. , 1996, American journal of respiratory and critical care medicine.

[52]  Shapiro Sd.  The pathogenesis of emphysema: the elastase:antielastase hypothesis 30 years later. , 1995 .

[53]  S. Shapiro,et al.  The pathogenesis of emphysema: the elastase:antielastase hypothesis 30 years later. , 1995, Proceedings of the Association of American Physicians.

[54]  D. S. St. Clair,et al.  Protective role of manganese superoxide dismutase against cigarette smoke-induced cytotoxicity. , 1994, Journal of toxicology and environmental health.