Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lung injury induced by intratracheal instillation of cadmium chloride (CdCl2) into the rat lung may serve as a model of human interstitial lung disease. In this study, CdCl2 solutions were instilled through a lobar bronchus into the left lung of the rat. Two doses (400 micrograms or 50 micrograms of CdCl2, each in 400 microliters of neutral saline) were used and the morphologic changes occurring during the first 7 days after a single exposure were documented by light and electron microscopy. With the higher dose, inflammatory cells appeared in the alveolar interstitium 1 day after CdCl2 administration. Edema and thickening of the alveolar walls were evident, as were damaged type I epithelial cells and denuded basement membranes. Fibrin was found in the air spaces. Within 2 days, inflammatory cells were seen in large numbers and fibroblasts were observed passing through gaps in the alveolar basement membranes into the air spaces. By 4 and 7 days after CdCl2, various forms of intraluminal fibrosis, including intrabronchiolar budding, mural incorporation, and obliterative changes, were observed. The contralateral lungs had normal-appearing architecture for all the time points investigated. In the lower dose exposure, gradients of alveolar damage were observed in which normal lung, interstitial fibrosis, and/or intraluminal fibrosis were seen within treated lungs. In the mildly damaged regions, interstitial fibrosis predominated, while in the more severely damaged regions, mural incorporation of the convoluted basement membranes was observed. The pulmonary fibrosis that developed appeared to be similar to some human interstitial lung diseases and may offer a system in which to study the regulation of collagen deposition and fibrosis development in these pathologic conditions.
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PMID:Intraluminal fibrosis induced unilaterally by lobar instillation of CdCl2 into the rat lung. 222 Oct 17

Fibrin deposition in the alveolar space and the lung interstitium is a prominent feature of many types of inflammatory pulmonary diseases. Cells of the monocyte/macrophage line are the primary cells supplying procoagulant activity in inflammatory lesions. In the present study we found that both lung alveolar macrophages (LAM) and bronchoalveolar lavage fluids (BALF) from humans contained procoagulant activities. The procoagulant in BALF was associated with membrane vesicles which sedimented at 100,000 g for 1 h. By electron microscopy the BALF ultrasediment was seen to consist almost exclusively of membrane material and this was confirmed by monitoring the content of different marker enzymes for specific subcellular structures. Using macrophage membrane markers, at least part of the BALF-ultrasediment was shown to be derived from LAM. On the basis of phospholipase C sensitivity, antibody neutralization and the site of action of the procoagulant in the sequential activation of coagulation factors, both the LAM-associated and the BALF-associated procoagulant activity was identified as thromboplastin (tissue factor) or thromboplastin-factor VII complexes. This suggests that alveolar macrophages and the LAM-derived thromboplastin-containing microvesicles may contribute to intraalveolar and interstitial fibrin deposition in vivo and probably also have consequences for the development of pulmonary fibrosis.
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PMID:Procoagulant (thromboplastin) activity in human bronchoalveolar lavage fluids is derived from alveolar macrophages. 231 34

Fibrin deposition is prominent in the course of several forms of pulmonary fibrosis. To elucidate the role of fibrin deposition and fibrinolysis in the process of pulmonary fibrosis, we studied bleomycin-induced fibrosis and the effect of urokinase on it. Beagle dogs were injected intramuscularly 20 times with bleomycin in doses of 2 and 6 mg/kg body weight every other day. Intravenous urokinase treatment was subsequently performed with 3,000 units daily for 40 days and 9,000 units twice daily for 70 days. Histopathologic examination of the lungs of dogs receiving bleomycin alone revealed fibrosis. The lungs of bleomycin-treated dogs which received urokinase had less severe fibrosis and this was confirmed by morphometry with planimetry and the point counting method. Urokinase treatment also diminished the increase of hydroxyproline content of the lung of bleomycin-treated dogs. Decrease of lung tissue fibrinolytic activity assayed by fibrin plate method in bleomycin-treated dogs was also prevented by urokinase. Intravenous urokinase, 24,000 units per day in divided doses, was administered daily in cancer patients with bleomycin treatment. Incidence of pulmonary fibrosis was decreased by urokinase. These data indicate that fibrin deposition and fibrinolysis may have an important influence on the fibrotic process in the lung.
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PMID:[Fibrin deposition and fibrinolysis in the pathogenesis of pulmonary fibrosis]. 279 52

Intra-alveolar fibrin is formed following lung injury and inflammation and may contribute to the development of pulmonary fibrosis. Fibrin turnover is altered in patients with pulmonary fibrosis, resulting in intra-alveolar fibrin accumulation, mainly due to decreased fibrinolysis. Alveolar type II epithelial cells (AEC) repair the injured alveolar epithelium by migrating over the provisional fibrin matrix. We hypothesized that repairing alveolar epithelial cells modulate the underlying fibrin matrix by release of fibrinolytic activity, and that the degree of fibrinolysis modulates alveolar epithelial repair on fibrin. To test this hypothesis we studied alveolar epithelial wound repair in vitro using a modified epithelial wound repair model with human A549 alveolar epithelial cells cultured on a fibrin matrix. In presence of the inflammatory cytokine interleukin-1beta, wounds increase by 800% in 24 hours mainly due to detachment of the cells, whereas in serum-free medium wound areas decreases by 22.4 +/- 5.2% (p < 0.01). Increased levels of D-dimer, FDP and uPA in the cell supernatant of IL-1beta-stimulated A549 epithelial cells indicate activation of fibrinolysis by activation of the plasmin system. In presence of low concentrations of fibrinolysis inhibitors, including specific blocking anti-uPA antibodies, alveolar epithelial repair in vitro was improved, whereas in presence of high concentrations of fibrinolysis inhibitors, a decrease was observed mainly due to decreased spreading and migration of cells. These findings suggest the existence of a fibrinolytic optimum at which alveolar epithelial repair in vitro is most efficient. In conclusion, uPA released by AEC alters alveolar epithelial repair in vitro by modulating the underlying fibrin matrix.
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PMID:Urokinase plasminogen activator released by alveolar epithelial cells modulates alveolar epithelial repair in vitro. 1641 81

Acute respiratory distress syndrome and acute lung injury for a part of a devastating syndrome characterized by acute onset, hypoxemia and bilateral infiltrates in the chest x-ray with absence of heart failure signs. Acute lung injury is the response of the lung to a local or systemic aggression, resulting in local inflammation and coagulation disorders, this leading to increased inflammatory pulmonary edema. Acute lung injury/acute respiratory distress syndrome are associated with increased procoagulant and reduced fibrinolytic activities mainly in alveoli and interstitial spaces in the lung. Fibrin deposits, which are the hallmark of early phase acute lung injury, stimulate fibroblast aggregation and collagen secretion, participating to the constitution of pulmonary fibrosis. The only clinical intervention found to have a significant impact on mortality in acute respiratory distress syndrome, despite the significant pro - gress in the understanding of the disease made over the past 10 years, is the use of low tidal volume ventilation. In severe sepsis, only recombinant human activated protein C administration has demonstrated a mortality reduction, together with faster improvement in respiratory dysfunction and shorter duration of mechanical ventilation. Future clinical trials should consider the potential benefit of anticoagulants administrated systemically or locally in the lungs to determine the role of anticoagulants in the treatment of acute pulmonary injury/acute respiratory distress syndrome.
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PMID:[Role of coagulation in acute pulmonary lesion physiopathology. Parallelism with sepsis]. 1860 38