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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary fibrosis induced by bleomycin is associated with accumulation of collagen and elastin in the lungs. The excess connective tissue proteins persist despite resolution of inflammation after cessation of treatment. In the present study, mild lung injury was produced in 9 juvenile baboons by twice-weekly injections of bleomycin to a total dose of 66 units/kg. Treated animals showed losses in body weight, lung volume, and diffusing capacity. Right middle lobectomies were performed in 3 animals shortly after cessation of bleomycin. Only minimal histologic changes were present, but lobar connective tissue protein concentrations and the rate of collagen synthesis were increased. Biopsies obtained in 3 additional animals 3 months later revealed similar changes. All animals were killed 6 months after cessation of treatment. Mild fibrosis was present, and lobar contents of collagen and elastin, as well as synthetic rates of collagen and elastin, remained elevated. Accumulation of lung connective tissue proteins in this model was associated with increased rates of synthesis that persisted after discontinuance of the drug.
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PMID:Bleomycin-induced diffuse interstitial pulmonary fibrosis in baboons. II. Further studies on connective tissue changes. 616 18

Pulmonary fibrosis was induced in rabbits by an intratracheal instillation of bleomycin. Histologically, at 2 weeks there was inflammation but only limited evidence of increased collagen deposition; at 8 weeks the inflammatory response had subsided and increased collagen deposition, characteristic of early interstitial fibrosis, was observed. Biochemical analyses showed bleomycin treatment caused marked increases in the total amounts of RNA, DNA, mixed protein, collagen and elastin when compared to controls (P less than 0.001 in all cases). Furthermore the increases were essentially complete by 2 weeks where the contents had increased by 110 +/- 13%, 60 +/- 11%, 148 +/- 12%, 94 +/- 15% and 89 +/- 11% respectively (P less than 0.001 in all cases). When collagen and elastin were expressed as concentrations with respect to wet weight, total protein or DNA content, the changes were not statistically significant. No changes were observed in the relative amounts of type I and type III collagen. It is concluded that: (1) compared to biochemical analysis, histology is relatively insensitive in detecting the early increases in connective tissue proteins; (2) measurements of lung collagen and elastin should be expressed as total lung contents wherever possible; the concentration of these proteins may remain unchanged, especially in the early stages of fibrosis, due to concomitant increases in other lung constituents; (3) changes in the relative amounts to types I and III collagens do not play a major role in the pathology of this form of pulmonary fibrosis.
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PMID:Biochemical and histological changes in pulmonary fibrosis induced in rabbits with intratracheal bleomycin. 617 45

Cross-linked elastin synthesis was measured in the intratracheal bleomycin model of interstitial pulmonary fibrosis by incorporation of 14C-lysine into the elastin-specific crosslinks, desmosine and isodesmosine. Detection of the labeled crosslinks was facilitated by development of a highly sensitive assay utilizing thin-layer electrophoresis. The results indicate that crosslinked elastin synthesis is significantly elevated from controls (p less than 0.05) at 1 to 3 weeks after exposure to bleomycin and returns to normal by 5 weeks. The increases in labeled elastin synthesis are not directly related to changes in either total lung protein synthesis or the pool size of the 14C-lysine. In comparison with collagen and glycosaminoglycan synthesis in this model of lung injury, maximal increases in cross-linked elastin formation occur later, but overlap with the elevated synthesis of these other connective tissue components. The marked increase from normal in cross-linked elastin synthesis in this model suggests that this tissue component is an important part of the fibrotic response of the pulmonary parenchyma and may play a role in the observed alterations in lung structure and function.
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PMID:Measurement of cross-linked elastin synthesis in bleomycin-induced pulmonary fibrosis using a highly sensitive assay for desmosine and isodesmosine. 619 45

72 cases of diffuse interstitial lung diseases were observed from 1969 to 1976. Specimens removed from 47 patients were subjected to the whole spectrum of reactions. According to variation of both elastin and collagen, the following groups were outlined: group A: mycobacteriosis, farmer's lung, sarcoidosis and silicosis; group B: chronic eosinophilic pneumonia, lymphocytic interstitial pneumonia, post-tuberculous pulmonary fibrosis, and group C: X-ray pneumopathy, desquamative interstitial pneumonia, sclerodermic pneumopathy and chronic pulmonary fibrosis (primary chronic fibroadenomyosis). Each of these groups presents a close relationship between histochemical, radiological, clinical and functional findings.
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PMID:Diffuse interstitial lung diseases: a histochemical approach. 623 29

This presentation reports on newer animal models and techniques that we and others have developed. These models attempt to predict in a reasonable experimental time frame the occurrence of structural changes in the lungs that are the basis of various chronic diseases. Since the major chronic diseases of the lung parenchyma involving what we think of as well-understood structural changes are pulmonary fibrosis and emphysema, I will discuss in detail ways of looking at effects of air pollutants on lung collagen and lung elastin metabolism.
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PMID:Biochemical alterations of lung structure as predictors of chronic lung disease. 665 17

In the normal, healthy lung, elastin production is restricted to periods of development and growth. However, elastin expression in the adult lung has been observed in some forms of pulmonary injury, including pulmonary fibrosis. Here, we report that elastin production is significantly increased within precise interstitial compartments of the lung in an experimental model of granulomatous lung disease. An increase in the number and volume of elastic fibers within the alveolar walls was apparent on histological examination of Verhoeff-van Gieson-stained sections of silicotic rat lungs. Quantitation of mature elastin cross-links indicated that silicosis was accompanied by a 17-fold increase in lung elastin content when compared with values from saline-treated controls. In situ hybridization for tropoelastin mRNA revealed that elastin production was absent from granulomatous lesions yet was prominent at nonfibrotic alveolar septal tips, where a high density of elastic fibers is seen in the normal lung. Immunohistochemistry indicated tropoelastin was being expressed by alpha-smooth muscle actin-containing cells. Transforming growth factor-beta was immunolocalized to granulomatous regions of the silicotic lung but was absent from regions showing increased tropoelastin expression. These data indicate that the reinitiation of tropoelastin gene expression is associated with granulomatous lung disease, and this expression leads to the aberrant accumulation of mature elastin in the lung.
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PMID:Increased elastin production in experimental granulomatous lung disease. 757 74

Sprague-Dawley rats were exposed for 6 h daily to 0.8 ppm of ozone and 14.4 ppm of nitrogen dioxide. Approximately 7 to 10 wk after the initiation of exposure, animals began to demonstrate respiratory insufficiency and severe weight loss. About half of the rats died between Days 55 and 78 of exposure; no overt ill effects were observed in animals exposed to filtered air, to ozone alone, or to nitrogen dioxide. Biochemical findings in animals exposed to ozone and nitrogen dioxide included increased lung content of DNA, protein, collagen, and elastin, which was about 300% higher than the control values. The collagen-specific crosslink hydroxy-pyridinium, a biomarker for mature collagen in the lung, was decreased by about 40%. These results are consistent with extensive breakdown and remodeling of the lung parenchyma and its associated vasculature. Histopathologic evaluation showed severe fibrosis, alveolar collapse, honeycombing, macrophage and mast cell accumulation, vascular smooth muscle hypertrophy, and other indications of severe progressive interstitial pulmonary fibrosis and end-stage lung disease. This unique animal model of progressive pulmonary fibrosis resembles the final stages of human idiopathic pulmonary fibrosis and should facilitate studying underlying mechanisms and potential therapy of progressive pulmonary fibrosis.
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PMID:A new model of progressive pulmonary fibrosis in rats. 834 14

Interstitial pulmonary fibrosis is characterized by increased production of connective tissue components, including collagen and elastin. The role of elastin turnover in pulmonary fibrosis is not clear, and it is not known whether elastin and collagen are regulated separately or together during the inflammatory process. Mice with bleomycin-induced pulmonary fibrosis were investigated to determine the temporal and spatial changes in localization of elastin mRNA expression, as well as to compare elastin mRNA expression with that of alpha 1(I) collagen mRNA expression. In control (saline-treated) lungs, elastin mRNA was detected by in situ hybridization in arterial walls. No signal was found in alveolar or airway walls or in pleura; alpha 1(I) collagen mRNA was detected in the tissue underlying the airway epithelium. An increase in elastin mRNA expression in muscular arteries was observed 3 days after bleomycin instillation. Expression was also seen in the adventitia of terminal airways and adjacent small blood vessels. Expression of alpha 1(I) collagen mRNA increased in the tissue underlying the airway epithelium. In the pleura, alpha 1(I) collagen mRNA expression was found, although no pleural thickening was evident. The alpha 1(I) collagen mRNA expression was particularly increased in the adventitia of terminal airways and in associated small blood vessels. Obvious in areas of fibrosis, elastin mRNA expression was occasionally increased in the pleura and airway wall 7 days after bleomycin treatment; alpha 1(I) collagen mRNA expression was generally stronger than elastin mRNA expression in areas of fibrosis and was frequently intense in the adventitia of airways and associated blood vessels. The fibrotic areas showed increased elastin mRNA expression 14 and 30 days after bleomycin treatment. The arteries in fibrotic areas showed normal elastin mRNA levels. In the areas of fibrosis and in the adventitia of airways and adjacent blood vessels, alpha 1(I) collagen mRNA expression was very high. In conclusion, lung elastin biosynthesis is markedly altered by bleomycin treatment. The localization and intensity of elastin mRNA expression is different from the expression of alpha 1(I) collagen mRNA.
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PMID:Differential expression of elastin and alpha 1(I) collagen mRNA in mice with bleomycin-induced pulmonary fibrosis. 856 73

Elastic fibres are present in lung structures including alveoli, alveolar ducts, airways, vasculature and pleura. The rate of lung elastin synthesis is greatest during fetal and neonatal development, and is minimal in the healthy adult. We have determined that glucocorticoids up-regulate fetal lung tropoelastin expression while concomitantly accelerating terminal airspace maturation. Because there is minimal turnover of elastin in healthy adult lung, the elastin incorporated into the lung early in development supports lung function for the normal lifespan. However, in the adult lung, in pathological circumstances such as emphysema or pulmonary fibrosis there may be reactivation of elastin expression. We have found in silica-induced pulmonary fibrosis that expression of tropoelastin is primarily increased in the walls and the septal tips of the alveolus, with modest increases in other compartments which normally express tropoelastin during development. This finding suggests that the mesenchymal cell of the alveolar wall increases tropoelastin expression during fibrotic disorders. In emphysema and fibrosis, elastin is present in abnormal-appearing, probably non-functional, elastic fibres, suggesting that the adult lung cannot recapitulate the elastic fibre assembly mechanisms operative during normal lung growth.
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PMID:Elastin in lung development and disease. 857 58

Transforming growth factor (TGF)-beta1 has been implicated in the pathogenesis of fibrosis based upon its matrix-inducing effects on stromal cells in vitro, and studies demonstrating increased expression of total TGF-beta1 in fibrotic tissues from a variety of organs. The precise role in vivo of this cytokine in both its latent and active forms, however, remains unclear. Using replication-deficient adenovirus vectors to transfer the cDNA of porcine TGF-beta1 to rat lung, we have been able to study the effect of TGF-beta1 protein in the respiratory tract directly. We have demonstrated that transient overexpression of active, but not latent, TGF-beta1 resulted in prolonged and severe interstitial and pleural fibrosis characterized by extensive deposition of the extracellular matrix (ECM) proteins collagen, fibronectin, and elastin, and by emergence of cells with the myofibroblast phenotype. These results illustrate the role of TGF-beta1 and the importance of its activation in the pulmonary fibrotic process, and suggest that targeting active TGF-beta1 and steps involved in TGF-beta1 activation are likely to be valuable antifibrogenic therapeutic strategies. This new and versatile model of pulmonary fibrosis can be used to study such therapies.
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PMID:Adenovector-mediated gene transfer of active transforming growth factor-beta1 induces prolonged severe fibrosis in rat lung. 925 74


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