[Alveolar lavage and pulmonary fibrosis caused by hard metals].
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Therapeutic irrigation
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Fibroblasts in healthy adult lung are quiescent, synthesizing little collagen. We studied lung biopsies from 30 patients with pulmonary fibrosis, using immunohistochemistry with monoclonal antibodies against the propeptides of type I collagen to localize fibroblasts actively synthesizing collagen. Adjacent sections were stained with antibodies to type III and IV collagen, fibrin, cytokeratin, plasma fibronectin, or EDIIIa-containing “cellular” fibronectin (cFN). In rapid pulmonary fibrosis, including the proliferative phase of diffuse alveolar damage, organizing pneumonia, and subacute idiopathic fibrosis, collagen-synthesizing cells were numerous in organizing exudate filling airspaces but were also seen in the interstitium of the alveolar walls, interlobular septa, and walls of blood vessels. The new matrix deposited in the airspaces also contained type III collagen and EDIIIa-containing fibronectin. In chronic pulmonary fibrosis, more than half of the biopsies showed foci of collagen synthesis and cFN deposition near the air-tissue interface. The foci were consistently localized outside remnants of basal lamina and therefore within airspaces. The results indicate that (1) fibrosis in chronic idiopathic pulmonary fibrosis results mainly from organization of exudate within airspaces, just as it does after acute lung injury, and (2) during this process, fibroblasts increase their synthesis of collagen and fibronectin coordinately. Foci of active matrix deposition provide evidence for the progressive nature of chronic pulmonary fibrosis.
Tissue Remodeling
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To show the clinical importance of cells containing FXIIIa in pulmonary fibrosis induced by bleomycin, the distributions of FXIIIa and collagenous components were investigated immunohistochemically in both normal lung tissues and those affected by bleomycin. In the normal tissues FXIIIa-containing cells were sparse, but they were numerous in the pulmonary fibrotic tissues, especially in the subpleural area and around the blood vessels of alveolar septa, where slight to moderate fibrosis was seen, and in the intra-alveolar fibrinous exudate. In the collagenous scar-like areas, however, these cells were fewer in number and their FXIIIa expression was depleted. These findings suggest that cells containing FXIIIa have an important role in the development of pulmonary fibrosis induced by bleomycin.
Factor XIIIa
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The pathological changes in idiopathic pulmonary fibrosis (IPF) typically start in subpleural lung regions, a feature that is currently not explained. IPF, as well as bleomycin-induced lung fibrosis, are more common in smokers. We hypothesised that carbon particles, which are major components of cigarette smoke that are transported to alveoli and pleural surface, might be involved in the development of subpleural fibrosis through interaction with pleural mesothelial cells. Carbon particles were administered to mice in combination with bleomycin through intratracheal and/or intrapleural injection and fibrosis was assessed using histomorphometry. Carbon administered to the chest cavity caused severe pleural fibrosis in the presence of bleomycin, whereas bleomycin alone had no fibrogenic effect. The pleural response was associated with progressive fibrosis in subpleural regions, similar to IPF in humans. Matrix accumulation within this area evolved through mesothelial-fibroblastoid transformation, where mesothelial cells acquire myofibroblast characteristics. In contrast, carbon did not exaggerate bleomycin-induced pulmonary fibrosis after combined intratracheal administration. This represents a novel approach to induce a robust experimental model of pleural fibrosis. It also suggests that carbon particles might be involved as a cofactor in the initiation and/or progression of (subpleural) pulmonary and pleural fibrosis. Mesothelial cells appear to be critical contributors to this fibrotic process.
Pleural cavity
Myofibroblast
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Objective By quantitative analysis and evaluating the pathomorphology and ultrastructural changes in various periods of rat pulmonary fibrosis model,the evident for the preventive effect and therapeutic mechanism in treating pulmonary fibrosis are offered.Methods Pulmonary fibrosis was made by non-exposure intratracheal injection of Bleomycin. The pathomorphology and ultrastructure were observed, the weight of lungs and rats were recorded, then the pulmonary index (PI) was evaluated. Results The PI increased during the pulmonary fibrosis progress. The most badly alveolar inflammation occur in at 7th day and the obvious shrink of alveolar cavity and increase of collagen fibers at 28th day were found by means of the quantitative analysis. The infiltrating inflammatory cells and the increase of collagen fibers were able to be seen under the light microscope. The ultrastructure in most of them showed that the collagen fibers in alveolar septum was obviously increased and the honeycomb shape of pulmonary structure destroyed. Type Ⅱ alveolar epithelial cells hyperplasia also be seen. Conclusion The pulmonary fibrosis model induced by Bleomycin is typical in the development of alveolitis to pulmonary fibrosis.
Alveolar Wall
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Type IV collagen
Myofibroblast
Alveolar Wall
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Abstract To determine the cellular and fibrogenic responses of the lung to long asbestos fibres, mice were instilled intratracheally with 0.1 mg of a sample of long crocidolite fibres. Animals were killed at intervals to 20 weeks with 3 H thymidine injected one h before death. Following bronchoalveolar lavage, an increase in polymorph neutrophils (PMN) and alveolar macrophages (AM) was found during the first week, accompanied by elevated glucosaminidase and alveolar protein levels. Although the PMN number dropped, some were always recovered by lavage to 20 weeks. Early multifocal necrosis of bronchiolar epithelium was followed by a large increase in labelling of epithelial cells and underlying fibroblasts. Epithelial overgrowth of luminal long fibres and inflammatory exudates was followed by giant cell and granuloma formation in the interstitium. After four weeks collagen levels were significantly increased and fibrosis was seen in these peribronchiolar locations. A few small fibres were observed in AM but no evidence of fibrosis was seen in alveolar walls. These findings suggest that injury to bronchial and bronchiolar epithelium allows long fibres to reach the interstitium where subsequent macrophage‐fibroblast interactions result in a severe fibrotic reaction that resembles the bronchiolar component of human asbestosis.
Asbestosis
Lung Fibrosis
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Silicosis, caused by the inhalation of crystalline silicon dioxide or silica, is one of the most severe occupational diseases. Persistent inflammation and progressive massive pulmonary fibrosis are the most common histological changes caused by silicosis. Association of epithelial-mesenchymal transition (EMT) of hyperplastic type II epithelial cells with the fibrotic events of pulmonary fibrosis has been suggested in in vitro silica-exposed cultured cell models, patients with idiopathic pulmonary fibrosis, and bleomycin-induced experimental models. Histological features of EMT, however, are not fully described in silicotic lungs in in vivo. The purpose of this study was to demonstrate EMT of hyperplastic type II epithelial cells in the developmental process of progressive massive pulmonary fibrosis in the lungs of rats exposed to silica. F344 female rats were intratracheally instilled with 20 mg of crystalline silica (Min-U-Sil-5), followed by sacrifice at 1, 3, 6, and 12 months after instillation. Fibrosis, characterized by the formation of silicotic nodules, progressive massive fibrosis, and diffuse interstitial fibrosis, was observed in the lungs of the treated rats; the effects of fibrosis intensified in a time-dependent manner. Hyperplasia of the type II epithelial cells, observed in the massive fibrotic lesions, dominated in the lungs of rats at 6 and 12 months after the treatment. Immunohistochemistry of the serial sections of the lung tissues demonstrated positive labeling for cytokeratin, vimentin, and α-smooth muscle actin in spindle cells close to the foci of hyperplasia of type II epithelial cells. Spindle cells, which exhibited features of both epithelial cells and fibroblasts, were also demonstrated with bundles of collagen fibers in the fibrotic lesions, using electron microscopy. Increased expression of TGF-β was shown by Western blotting and immunohistochemistry in the lungs of the treated rats. These findings suggested that enhanced TGF-β expression and EMT of hyperplastic type II epithelial cells are involved in the development process of progressive massive pulmonary fibrosis during silicosis.
Silicosis
Myofibroblast
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Pathogenesis
Infiltration (HVAC)
Metaplasia
Alveolar Wall
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Objective To observe pulmonary fibrosis in severe acute respiratory syndrome (SARS) and to discuss the mechanisms of pulmonary fibrosis in SARS. Methods Hematoxylin and Eosin staining (HE), histology staining and immuno-histochemical staining (SP methods) were used to investigate the lungs from 4 autopsy cases. Antibodies against collagen type Ⅲ, α-smooth muscle actin(α-SMA), Fas, FasL and transforming growth factor β1(TGF-β1) were used for immunohistochemical studies. Results All these four lung tissues showed different degree of pulmonary fibrosis, including the organization of exudative fibrin, glomerulus-like fibrosis in alveolar spaces, the thickening of the alveolar septum, proliferation of fibroblasts, the hyperplasia of collagen fibers and the consolidation of lungs. Sirius red staining and collagen type Ⅲ staining showed the type Ⅲ and the type Ⅰ collagen fibers were the main components of the hyperplastic collagen fibers. α-SMA were expressed in fibroblasts, immunoreactivity to Fas, FasL, TGF-β1 were all positive and located in plasma of pneumocytes, macrophages and lymphocytes. Conclusions The pulmonary fibrosis can be observed early in SARS patients and the pathogenesis may be involved in the co-effect of many effective cells, inflammatory mediators and cytokines.
Sirius Red
Van Gieson's stain
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AIM: To investigate the presence and distribution of advanced glycation end products (AGE) in pulmonary fibrosis. METHODS: Lung tissue samples obtained from seven necropsy cases with idiopathic pulmonary fibrosis and seven with normal pulmonary parenchyma were examined immunohistochemically with a monoclonal antibody specific for AGE: 6D12. We also tested three cases with diffuse alveolar damage. RESULTS: All the specimens from cases with pulmonary fibrosis and diffuse alveolar damage showed strong AGE expression on macrophages. Lung specimens from normal parenchyma showed positive AGE immunoreactivity on macrophages from only two of seven cases. CONCLUSIONS: These findings suggest that AGE modified proteins accumulate in alveolar macrophages in patients with diffuse alveolar damage and idiopathic pulmonary fibrosis.
Parenchyma
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