title: Cell death, remodeling, and repair in chronic obstructive pulmonary disease?
abstract: Apoptotic cells can be detected in the parenchyma and airways of patients with chronic obstructive pulmonary disease (COPD) in greater numbers than seen in normal lungs or those from smokers without COPD. Implications include more apoptosis and/or decreased clearance of apoptotic cells. Both epithelial and endothelial cells become apoptotic. What role does the apoptosis play in the emphysema or small airway alterations seen in COPD? In simple terms, loss of cells by apoptosis would be expected to accompany, or perhaps initiate, the overall tissue destruction normally believed responsible. Indeed, direct induction of apoptosis in pulmonary endothelial or epithelial cells in rodents is accompanied by emphysematous changes. On the other hand, apoptotic cells are normally removed from tissues rapidly with minimal tissue response, to be followed by cell replacement to maintain homeostasis. The presence of detectable apoptotic cells, therefore, may imply defects in these clearance mechanisms, and, in keeping with this hypothesis, there is increasing evidence for such defects in patients with COPD. Mice with abnormalities in apoptotic cell removal also tend to develop spontaneous "emphysema." A reconciling hypothesis is that recognition of apoptotic cells not only leads to removal but also, normally, to signals for cell replacement. If this latter response is lacking in COPD-susceptible smokers, defects in normal alveolar or small airway repair could significantly contribute to the structural disruption. The concept puts emphasis on defective repair as well as initial injury (i.e., persistent alteration of dynamic tissue homeostasis, as a key contributor to COPD), with, it is hoped, additional approaches for mitigation.
authors.affiliation: National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA. hensonp@njc.org
authors.forename: Peter M
authors.initials: PM
authors.lastname: Henson
authors.forename: R William
authors.initials: RW
authors.lastname: Vandivier
authors.forename: Ivor S
authors.initials: IS
authors.lastname: Douglas
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001980:Bronchi / Q000166:cytology* / Q000293:injuries; D004195:Disease Models, Animal; D004646:Emphysema / Q000503:physiopathology; D006706:Homeostasis; D006801:Humans; D051379:Mice; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology*; D012038:Regeneration / Q000502:physiology*; D020545:Respiratory Mucosa / Q000166:cytology* / Q000293:injuries