Cigarette smoke inhibits alveolar repair: a mechanism for the development of emphysema.
Classically, emphysema has been believed to develop when mediators of tissue injury exceed protective mechanisms within the lung. Evidence also supports the concept that tissue destruction represents a balance between tissue injury and tissue repair. In this context, cigarette smoke is directly toxic to cells within the lung and can impair the repair functions of fibroblasts, epithelial cells, and mesenchymal cells. This may occur in the absence of overt cytotoxicity and may result from alteration of selected biochemical pathways. A variety of repair functions can be affected, including chemotaxis, proliferation, production of extracellular matrix, and remodeling of extracellular matrix. Finally, cigarette smoke can damage DNA but can also compromise apoptosis. As a result, DNA repair mechanisms can be initiated, leading to recovery of cells that potentially contain somatic cell mutations. This pathway may contribute not only to the development of cancer but to the persistent abnormalities in tissue structure that characterize chronic obstructive pulmonary disease. Understanding the mechanisms that mediate normal tissue repair and understanding the bases for altered tissue repair in the face of cigarette smoking offer new opportunities designed to address the structural alterations that characterize chronic obstructive pulmonary disease.
Rennard
Stephen I
SI
University of Nebraska Medical Center, Pulmonary and Critical Care Medicine, 985125 Nebraska Medical Center, Omaha, NE 98198-5125, USA. srennard@unmc.edu
Togo
Shinsaku
S
Holz
Olaf
O
D000818:Animals; D017209:Apoptosis; D004249:DNA Damage; D004260:DNA Repair; D004646:Emphysema / Q000503:physiopathology*; D006801:Humans; D011650:Pulmonary Alveoli / Q000293:injuries* / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology; D011658:Pulmonary Fibrosis / Q000503:physiopathology*; D012907:Smoking / Q000009:adverse effects* / Q000503:physiopathology; D014212:Tretinoin / Q000494:pharmacology; D014945:Wound Healing / Q000502:physiology
D014212:Tretinoin