[The role of oxidative stress in the pathogenesis of pulmonary emphysema].
OXIDATIVE PULMONARY DAMAGE: The pathogenesis of pulmonary emphysema is incompletely understood. Nearly 90% of all patients with chronic obstructive pulmonary diseases are smokers. Cigarette smoke is a rich source of oxidants. Oxidative stress increases oxidant generation, which cannot be neutralized with antioxidant defense mechanisms. Lipids, proteins and deoxyribonucleic acid are components of the cell that are most sensitive to oxidative damage. Oxygen radicals can modify amino acid side chains, form protein aggregates, cleave peptide bonds, and make proteins more susceptible to proteolytic degradation. It has been shown that neutrophils have a principal effector role in pulmonary tissue damage. Neutrophil elastase can damage air spaces by degrading elastin, and a variety of extracellular membrane proteins, proteoglycans, and glycoproteins. Neutrophil elastase can also stimulate inflammation by increasing interleukin-8 synthesis. Additionally, neutrophil elastase can activate or inactivate inhibitors of neutrophil collagenase, and secretory leukoprotease proteinase inhibitor. Apart from neutrophils, oxidative stress causes activation of other phagocytes and severe inflammatory response ensues. LIPID PEROXILATION AND PULMONARY EMPHYSEMA: Except protein oxidation and lipid peroxidation, oxidants may disturb signal transmission in the cells, as well as normal cell membrane function and function of organelles. Modified structure of deoxyribonucleic acid may cause mutations, which in absence of repairation enzyme activity lead to cell injury. IRON AND OXIDATIVE STRESS: Iron metabolism is also important in the development of pulmonary emphysema due to its role in production of some oxidants.
Vucević
Danijela
D
Medicinski fakultet, Beograd, Institut za patolosku fiziologiju.
Radosavljević
Tatjana
T
Zunić
Snezana
S
Dordević-Denić
Gordana
G
Pesić
Branislav C
BC
Radak
Dorde
D
D006801:Humans; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation; D018384:Oxidative Stress; D011656:Pulmonary Emphysema / Q000378:metabolism / Q000503:physiopathology*
D007501:Iron