Nature Medicine 11, 471 - 472 (2005)
DOI: 10. 1038/nm0505-471
authors of Yale University, Department of Medicine, New Haven, Connecticut 06520, USA. Ceramides lipid mediator contributes to tissue destruction in emphysema by promoting apoptosis of structural cells in the lungs. This finding challenges the conventional hypothesis of the pathogenesis of emphysema (
). Chronic bronchitis and emphysema are closely associated with cigarette smoking and outdoor cooking, and pressing unmet medical needs worldwide. In the United States, these diseases affect more than 16 million people, another 50 million at risk under the influence of cigarette smoke. In China, 1. 5000000 people projected to die from these diseases each year over the next 50 years. In contrast, the striking impact on society, we are completely absent in pharmacological agents that alter the natural history of disease and decrease the rate of loss of lung function. This deficiency is due, largely, in our limited knowledge of the pathogenesis of the disease. In this issue Petrakova and colleagues solve this urgent need. They show that ceramides lipid mediator appear apoptosis of cells in the lungs of mice, leading to pulmonary emphysema. The authors further support the relevance of these data to humans, shows that ceramides upregulated in the lungs of patients with bronchitis and emphysema. Chronic bronchitis and emphysema overlapping conditions that often occur simultaneously, and, consequently, will be combined under diagnosis of COPD (chronic obstructive pulmonary disorder). Chronic bronchitis is diagnosed in patients with inexplicable cough and sputum production that lasts for more than two years and can not be associated with any other disorder. Light from the people with the disease have increased the number and size of mucus glands, a condition called mucous metaplasia. Emphysema is defined pathologically based on the destruction of alveolar walls, the site in the lungs, where absorption of oxygen and removing carbon dioxide occurs. Localized fibrosis and collagen and violation occurs, and many leukocyte populations contribute to inflammation and tissue infiltration in COPD tissues. In 1960, protease antiprotease hypothesis was the dominant concept in the pathogenesis of emphysema. This theory assumes that the 'shield' antiprotease protects normal day in day light effects that can increase the response easy proteolytic. It also suggests that emphysema occurs when inflammation or antioxidants cause an increase or decrease of proteases in antiproteases. Due to the popularity of CD8
regulated genes of T cells 1T helper type 1 (T. According to the theory, protease excess may damage the matrix, which generates a small "holes", areas of local attenuation, or both. With repeated trauma, holes merge, leading to rupture of alveolar walls. important to note that endothelial cell damage and alveolar epithelial cells of the primary events that traditionally are not part of this concept. Although protease antiprotease hypothesis was useful for design studies of the pathogenesis of emphysema is now clear it explains only some aspects of this disease. recent alternative hypothesis was entertained. This hypothesis suggests that damage cells, causing apoptosis of structural cells in the lungs is a major event in the pathogenesis of emphysema .. Later studies showed that apoptosis depends on emphysema lung induced blockade of vascular endothelial growth factor cells (VEGF) and activated caspase vnutrilehochnoho Administration 3 (link
). This work also showed that, unlike the standard conceptualization, apoptosis of structural cells in the lungs is not soft events . Instead, apoptosis contributes to the accumulation of local protease that can feed to the degradation of proteins in the matrix are the alveolar walls. It is clear from these studies that the alveoli depends on the integrity of endothelial and epithelial cells with loss or lead to structural changes and possibly emphysema. different molecular mediators involved in the pathogenesis of emphysema. According to the protease antiprotease hypothesis and the power of modern molecular biology, these studies were directed almost exclusively on proteins that function as proteases and antiproteases. These studies showed that the number of proteases, including neutrophil protein granules, matrix metalloproteinazy
and cathepsin involved in the degradation of collagen, elastin and other proteins of the matrix that occurs in emphysema. unique cathepsin-mediated apoptosis of epithelial and the way it was shown that the contribution leads to emphysema caused by T. In all cases, these responses are modulated proteolytic batteries including antiproteases
-1 antitrypsin deficiencyinduced emphysema. Ceramide is strictly regulated sfinholipidiv second conciliator. molecules made by different tissues in response to several stimuli, including endotoxins, oxidative stress and cytokines. Ceramide coordinates responses to stress modulates oxidative and proliferative responses and is a potent inducer of apoptosis. According to this property Petrakova
al. investigated the importance of ceramides in the pathogenesis of emphysema. Their research shows that it ceramides critical mediator of alveolar destruction. To show this, the authors inhibits the enzymes control
re-synthesis of ceramides and noted that the interference prevented apoptosis of alveolar cells, oxidative stress and emphysema in the mouse VEGF-blockade emphysema model. authors also found that ceramides induced emphysema when buried in the lungs of mice, and that stimulation sfynhozyna-1 phosphate, a downstream product of the metabolism of ceramides, which inhibit ceramides to prevent lung apoptosis. next step was to go beyond the mouse and watch the people. These studies have shown that lung ceramides were increased and qualitatively altered in lung tissue from individuals people with smoking-induced emphysema lasix 15 mg. These exciting research for several reasons. They primarily involve non-protein mediator of apoptosis in the pathogenesis of emphysema. In addition, in determining ways of biosynthesis of ceramides and pathways that regulate its effector properties (
), they determine the number of sites where measures may be aimed at trying to control pulmonary emphysema. Finally, given that the ceramides is also in the pathogenesis of atherosclerosis, these studies support the concept that abnormalities ceramides generalized response to the effects of cigarette smoke, and that similar mechanisms of pathogenic contribute to the pathogenesis of COPD, atherosclerosis and other cigarettes, smoking related diseases. complete understanding of the deposits ceramides in emphysema will require further investigation between ceramides changes, tissue proteolysis and inflammation. In particular, a better understanding of the relationship between T
1, inflammation and cathepsin-mediated apoptosis is important. It is however clear that from now on, apoptosis and lipid mediators must be taken into account when trying to understand the pathways leading to alveolar destruction and emphysema. Petrakova, I., et al . Nat. Med. 11, 491498 (2005) |.
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