[Pathogenesis of chronic obstructive pulmonary disease. Cellular mechanisms (part I)].
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Smoking is considered the major cause of the disease. All smokers develop airway inflammation through oxidative stress with macrophages, neutrophiles, lymphocytes, eosinophils, NK-cells and mediators involved. Macrophages through the activation of Nuclear Factor kappa B (NF.-kappaB) release proinflammatory mediators, lymphocyte chemotactic agents and elastolytic enzymes, activate neutrophil driven serine proteases and GM-CSF. Neutrophiles release IL-8 which in turn recruits neutrophils to the airways. In response to cigarette smoke lung epithelium may release TNF-alpha, TGF-beta, IL-1beta, GM-CSF, IL-8 reactive oxygen species (ROS). Increased number of lymphocyte T CD8+ and CD4+ subpopulations may lead to lung epithelium cells apoptosis and necrosis through perphorines and granzyme-B and TNF-alpha activation. Moreover, increased expression of IL-6, IL-10, IL-12, IL-13, and INF-gamma is observed. Authors indicate the possibility of new treatment strategies such as: agents directed against adhesion molecules, chemokines, phosphodiesterase 4, p38 MAPK, NF.-kappaB phosphoinositide-3-kinase gamma, TGF-beta, NOS synthase, serine proteinases and matrix metalloproteinases.
Mróz
Robert M
RM
ELEGI/Colt Laboratories, Centre for Inflammation Research, The University of Edinburgh, Edynburg, Wielka Brytania.
Szulakowski
Patryk
P
Pierzchala
Wliadysław
W
Chyczewska
Elzbieta
E
MacNee
William
W
D015703:Antigens, CD / Q000276:immunology; D015415:Biomarkers; D016207:Cytokines / Q000276:immunology / Q000502:physiology*; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000503:physiopathology*
D015703:Antigens, CD; D015415:Biomarkers; D016207:Cytokines