A hypothesis for the initiation of COPD.
Chronic obstructive pulmonary disease (COPD) is generally thought to depend on an aberrant immune response to a noxious or infectious agent, which may cause chronic inflammation. However, the initiation of this abnormal response is not fully understood. Here, we propose a new hypothesis for the beginning of COPD, that the immune response to inhaled agents, mainly cigarette smoke, is directed toward the airway epithelium, due to oxidative DNA damage of the lung epithelial barrier cells (LEBCs). The steps of this model are as follows. 1) Cigarette smoke induces oxidative DNA damage of LEBCs. 2) The acquired mutations are expressed at the microsatellite DNA level of LEBCs. 3) The altered LEBCs are recognised by dendritic cells (DCs) as "nonself". DCs travel, with the new information, to the lymph nodes, presenting it to the naïve T-lymphocytes. 4) A predominant CD8+ cytotoxic T-lymphocyte proliferation occurs. The CD8+ cells, by releasing perforin and granzymes, attack the altered LEBCs activating cell death cascades. Obviously, the above scenario needs further experimental exploration. However, it is an attractive model for the initiation of the abnormal inflammation in COPD, comprising oxidative DNA damage of LEBCs and host immune response.
Tzortzaki
E G
EG
Department of Thoracic Medicine, University Hospital, Medical School, University of Crete, Heraklion 71110, Greece. tzortzaki@med.uoc.gr
Siafakas
N M
NM
D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016923:Cell Death; D004249:DNA Damage; D003713:Dendritic Cells / Q000166:cytology; D004848:Epithelium / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation; D008168:Lung / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology* / Q000628:therapy*; D012907:Smoking; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology
D010100:Oxygen