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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Titanium dioxide (TiO2) dust has generally been regarded as a "nuisance dust" in experimental animals and men. In this experiment, 16 dogs were exposed intratracheally to TiO2 dust for 9-15 months. The scanning electron microscopy with energy dispersive analysis of X-ray (SEM-EDAX), performed to identify the elemental composition of dust particles used in the study and in the focal lesions of the lungs, showed that dust particles were nearly pure titanium. Dust in the lung deposited mainly in the respiratory bronchioles and adjacent alveoli, with many alveoli filled by compacted dust particles. The pulmonary responses consisted of slight alveolitis, centrilobular emphysema, focal collapse of alveoli, and fibroblast hyperplasia with a few collagen fibres surrounding some of the TiO2-dust foci. Electron microscopically, many alveolar macrophages with intact nuclei contained a great amount of dust particles in their lysosomes, and in the dust foci, most of type I pneumocytes disappeared and type I pneumocytes showed hyperplasia. The alveolar subepithelial basement membrane were markedly thickened and bundles of collagen fibres were formed in the interstice. These findings suggest that TiO2 dust is one of the sorts which probably induce mild lung fibrosis in case a large amount is deposited in the lung tissue.
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PMID:[Pathogenic effects of titanium dioxide dust on the lung of dogs--a histopathological and ultrastructural study]. 279 52

Chronic elastolytic activity in the lung is currently believed to be a major factor in pathogenesis of emphysema. Collagenase may have similar role in disorganizing lung collagen network, leading to fibrotic lung diseases (FLD). The possible involvement of collagenase in FLD is suggested by: 1) an increase collagenolitic activity in bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis or adult respiratory distress syndrome; 2) the accumulation and the activation of cells able to produce collagenases in FLD: fibroblasts, macrophages, neutrophils and eosinophils. However the exact role of collagenase in FLD is still unknown: it could inhibit neocollagen deposition, limiting fibrotic process or lead to further destruction of collagen network. Recent data suggest that genomic macrophage activation (such the proto oncogene c-SIS) may lead to several cellular events: 1) increase number and activation of fibroblasts with collagen synthesis; 2) increase collagenase production resulting of accumulation and activation of fibroblasts, macrophages, neutrophils. So we conclude that such a genomic macrophage activation may be the major factor contributing to the collagen network damage leading to lung tissue fibrosis.
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PMID:[Collagenase and diffuse interstitial pneumopathy]. 285 67

It has been reported that infections with Legionella pneumophila can lead to chronic inflammatory and fibrotic reactions in the human lung. To better characterize the nature of the residual abnormalities caused by this bacterium, we inoculated Syrian hamsters intratracheally with 10(8) serotype 1 L. pneumophila organisms and assessed histologic, functional, and biochemical changes at intervals up to 180 days. Acutely, L. pneumophila caused an intense alveolar macrophage (AM) and polymorphonuclear leukocyte (PMN) response within the lower air spaces, air-filled lungs were noncompliant, and there was an associated 25 to 50% increase in the lung content of collagen and elastin after 10 days. An inflammatory response, consisting principally of AM and centered around the terminal bronchioles, was still prominent in some infected lungs after 90 and 180 days, and the severity of the inflammation was correlated with a persistent restrictive defect in the elastic behavior of the lung. However, by histologic examination, fibrosis was not prominent, and the more representative abnormality was one of mild, diffuse air-space enlargement. Frank emphysematous changes were present focally in some lungs. In addition, an irregularly distributed lymphocytic infiltrate and goblet cell metaplasia were present in the larger bronchi of infected animals. We conclude that a single infection with L. pneumophila is capable of causing long-term inflammatory reactions in the lung, with morphologic features of both fibrosis and emphysema.
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PMID:Long-term pulmonary sequelae after Legionella pneumophila infection in the hamster. 293 77

Exposure of animals to oxidant gases produces a mild emphysema, and O2-derived free radicals are capable of degrading connective tissues in vitro. It is postulated that degradation of connective tissue by O2-derived free radicals leads to emphysema in these models. To determine whether exposure of lung tissue slices to an oxidant gas results in degradation of collagen and to investigate factors mediating this degradation, we exposed lung tissue slices from normal rats to hyperoxia (95% O2, 5% CO2) and measured hydroxyproline release into the medium. After a 4-h exposure, the hydroxyproline released was 5.3 +/- 0.2 micrograms/g lung tissue (n = 10) in normoxia and 8.1 +/- 0.6 micrograms/g tissue (n = 13) in hyperoxia (p less than 0.05), suggesting degradation of collagen. The addition of 0.1% trypsin to the initial incubation medium caused a synergistic increase in hydroxyproline release from O2-exposed slices: normoxia/trypsin, 46.2 +/- 3.6 micrograms/g tissue (n = 10); hyperoxia/trypsin, 61.4 +/- 3.6 micrograms/g tissue (n = 11) (p less than 0.05). The addition of proteinase inhibitors completely suppressed the O2-induced release of hydroxyproline, suggesting that proteolytic enzymes are involved in hyperoxia-mediated degradation of lung collagen.
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PMID:Degradation of collagen in lung tissue slices exposed to hyperoxia. 303 77

Recent concepts on the mechanisms of aging of extracellular matrix (EM) are reviewed as well as its involvement in age-associated diseases. Cell differentiation, histogenesis and organogenesis can be analyzed in terms of the program of the biosynthesis of EM macromolecules during development, maturation and aging. The most important biological role of EM is the integration of cells in tissues, of tissues in organs and of organs in the whole organism. EM can directly influence cell behavior through the contact between EM and the genome mediated by structural glycoproteins (fibronectin, laminin, elastonectin, etc.) interacting with other EM macromolecules (collagen, proteoglycans, elastin) and the cytoskeleton by trans-membrane receptors (integrins). Most age-associated diseases exhibit a deviation (qualitative or quantitative) from the normal program of EM biosynthesis. Three examples are analyzed in some detail: atherosclerosis, diabetes and malignant tumors. The degradation of elastic fibers catalyzed by cellular elastase-type enzymes is observed in atherosclerosis and also in emphysema and skin aging. Several of these enzymes were isolated and characterized from platelets, fibroblasts, smooth muscle cells and lipoproteins. The biosynthesis of some of them increases with age and facilitates cell migration. Plasma fibronectin increases with age exponentially. This increase is absent or strongly attenuated in diabetes and some cancers. Tissue fibronectin increases in diabetes, Werner syndrome and in the peritumoral desmoplastic reaction while most tumor cells can no more retain fibronectin on their membrane facilitating their movement in the organism. These examples demonstrate the importance of the study of cell matrix interactions for gerontology.
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PMID:Aging of the extracellular matrix and its pathology. 328 58

To determine whether lung elastin is lost during the evolution of cadmium-induced air-space enlargement with pulmonary fibrosis, the lung elastin of 5- to 7-day-old golden Syrian hamster pups was radiolabeled by giving [3H]valine. At maturity, a single intratracheal instillation of 0.5 ml of 0.025% CdCl2 solution was given. Lung mechanics, histologic examination, and biochemistry were studied 5, 10, 21, 42, 105, and 180 days after the cadmium treatment. The animals developed fibrosis and air-space enlargement with decreased lung volumes, compliance, and forced expiratory flow; their functional residual capacity was increased. The total lung collagen and total lung elastin were increased, but there was no loss of radiolabel in lung elastin. We conclude that CdCl2-induced air-space enlargement with pulmonary fibrosis is not accompanied by loss of neonatally formed lung elastic fibers. We hypothesize that air-space enlargement with fibrosis represents a stereotyped response of the lung to fibrosing injuries, which we hypothesize is due to forces from more fibrotic and atelectatic areas causing overdistension of less abnormal air spaces. The air-space enlargement of fibrosing human diseases such as sarcoidosis and eosinophilic granuloma may have a similar basis. Evidence is reviewed that human centrilobular emphysema may be a form of focal air-space enlargement with interstitial fibrosis; there may be mechanisms in addition to elastase-antielastase imbalance that cause human emphysema.
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PMID:Cadmium-chloride-induced air-space enlargement with interstitial pulmonary fibrosis is not associated with destruction of lung elastin. Implications for the pathogenesis of human emphysema. 335

Male mice with the sex-linked mutation Blotchy (Blo) have a defect in copper metabolism which results in deficient activity of a number of copper-containing enzymes. Inbred Blo/y mice spontaneously develop lung abnormalities which resemble emphysema and often die of ruptured aortic aneurysm. Lung, tail tendon, and tibial bone collagens from inbred Blo/y and their normal (+/y) litter mates were reduced with standardized [3H]NaBH4, acid and alkaline hydrolyzed, and chromatographed in order to quantify the aldehydic crosslink precursors, and the labile reducible and nonreducible stable mature covalent intermolecular crosslinks. Reducible lung collagen crosslinks were markedly (60%) decreased in the Blo/y mice and few, if any, mature nonreducible crosslinks were present. Total aldehydes were also decreased (65%) when Blo/y was compared to +/y. In tail tendon and bone, collagen crosslinks were decreased by only 28% and 15%, respectively. Selectively severe lack of activity of the copper-dependent enzyme level oxidase in lung with only partial lack in tendon and bone could account for the results obtained. Alternatively, insufficient reducible crosslinks, coupled with increased collagen turnover in the lung could prevent formation of the more mature stable crosslinks required to provide a proper connective tissue framework for the Blo/y lung.
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PMID:Structural crosslinking of lung connective tissue collagen in the blotchy mouse. 356 65

Furoyl saccharin, a novel heterocyclic acylating agent which has been previously found to possess a potent inhibitory capacity in vitro for elastase and other serine proteases, has been investigated in vivo in two acute animal models of emphysema. In hamsters, intratracheal (i.tr.) administration of 0.1 mg porcine pancreatic elastase resulted seven days later, in a 42% increase of the mean linear intercept (Lm). Addition of 0.3 mg to 0.3 mg furoyl saccharin to elastase exhibited a partial, not dose-related, but statistically significant inhibition of the increase of LM. Addition of 1 mg furoyl saccharin (equivalent to a dose of 12.5 mg/kg) completely abolished the increase in Lm. In the rabbit i.tr. instillation of 3.7 mg porcine pancreatic elastase induced within seven days, a 48% increase of the Lm, a 27% decrease of the internal surface area (ISA) of the lungs and a 33% decrease of the ISA corrected to an arbitrary total lung volume of 70 ml (ISA70). Furoyl saccharin given i.tr. 15 min prior to elastase at the doses 3, 10 and 20 mg prevented significantly in a dose-related manner, the changes in Lm, ISA and ISA70. The highest furoyl saccharin dose (equivalent to a dose of 10.8 mg/kg) completely protected against the emphysematous lesion. Additionally furoyl saccharin (20 mg i.tr.) prevented in the rabbit model the depletion in lung insoluble elastin and the increase in salt soluble collagen induced by the elastase administration. These results show that furoyl saccharin also in vivo has a marked antielastase activity.
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PMID:Effect of the novel synthetic protease inhibitor furoyl saccharin on elastase-induced emphysema in rabbits and hamsters. 363 28

A neonatal rat aorta smooth muscle cell culture system with a unique elastin-rich extracellular matrix was used as a model substrate for elastases. To study the susceptibility to solubilization of insoluble elastin, cultures were incubated in the presence of human neutrophil elastase (HNE) or porcine pancreatic elastase (PPE) and in the absence of serum for periods up to 45 min. Both the incubation media and cell layers were then assessed for elastin and collagen markers, total protein, and lactate dehydrogenase (LDH). Although HNE and PPE exhibited comparable activity against elastin purified from the cell layer, HNE exhibited a 6.7- to 25-fold reduction in its elastin solubilizing activity using intact cell layers as compared with the purified elastin, whereas PPE exhibited only a 1.5- to 2.5-fold reduction. This effect could not satisfactorily be explained as preferential inhibition of HNE activity in the culture system, because the amount of protein solubilized by HNE was 59% that of PPE. The mean elastin content of PPE-solubilized protein was 110% that of the elastin content of the corresponding cell layer; the value for HNE-solubilized protein was only 16%. Thus, the amount of elastin per microgram of solubilized protein for HNE was 15% that for PPE. Possible explanations for the greatly diminished elastolytic activity of HNE in the culture system include the preference of HNE for other substrates in the cell layer, the inability of HNE to penetrate sufficiently into the cell layer, and the presence of sulfated glycosaminoglycans in the vicinity of the elastin that act in an inhibitory fashion. Although there was extensive proteolytic damage to the extracellular matrix, LDH and DNA measurements indicated that little loss of cells or cell viability occurred. The observed differences in elastolytic activity of HNE and PPE in the culture system parallel the relative emphysema-inducing potency of the elastases in the hamster model of elastase-induced emphysema.
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PMID:Elastin in a neonatal rat smooth muscle cell culture has greatly decreased susceptibility to proteolysis by human neutrophil elastase. An in vitro model of elastolytic injury. 366 86

The effect of starvation on lung mechanics, morphometry, and levels of connective tissue components was determined in young adult golden Syrian hamsters. A base-line control, fed control, and starved group were studied. Fed group animals increased body weight by 13%, but dry lung weight did not increase above that of the base-line controls. The total lung capacity when transpulmonary pressure was at 25 cmH2O (TLC25) also increased by 20% above base-line controls. The mean TLC25 of the starved group was greater than that of the base-line control group but less than that of the fed control group (P less than 0.05). Volume-corrected air-filled volume pressure (VP) curves of the three groups were similar. Volume-corrected saline-filled VP curves were identical in the three groups. Total lung collagen, elastin, glycosaminoglycan, and protein were similar in the three groups. Air space size was significantly increased and mean internal surface area was significantly decreased in the starved group compared with the base-line and fed controls. No evidence of alveolar wall destruction was evident by light or electron microscopy. We conclude that severe starvation of young adult hamsters produces air space enlargement without changes in lung elastic recoil. The mechanism of alveolar wall remodeling is not yet understood in this model of emphysema.
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PMID:Lung mechanics and connective tissue levels in starvation-induced emphysema in hamsters. 374 Mar 10


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