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

Administration of amiodarone, although often lifesaving, is associated with pulmonary side effects. Patients with amiodarone pulmonary toxicity can present with either a chronic disorder that suggests pulmonary fibrosis or a more acute process. Mechanisms of acute pulmonary injury resulting from amiodarone are unclear. Previous studies have demonstrated that the drug is preferentially concentrated in alveolar macrophages. In the present study, the authors examined whether in vitro exposure to amiodarone resulted in alteration of rat alveolar macrophage superoxide, leukotriene B4, or fibronectin release. In addition, the authors assessed whether macrophages were ultrastructurally altered by in vitro amiodarone exposure. Twenty four hour exposure to therapeutic tissue concentrations of amiodarone resulted in enhancement of phorbol myristate acetate-stimulated macrophage superoxide release. In addition, 48 hours exposure to amiodarone caused a dose-dependent inhibition of spontaneous fibronectin release by macrophages. Macrophages exposed to 48 hours of 10 micrograms/ml amiodarone were ultrastructurally abnormal, containing lamellar inclusions and demonstrating a large degree of vacuolization. The authors concluded that alveolar macrophages are very sensitive to therapeutic tissue concentrations of amiodarone. Alteration of macrophage mediator release by amiodarone may be one mechanism for lung damage induced by the drug.
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PMID:Effects of in vitro amiodarone exposure on alveolar macrophage inflammatory mediator production. 133 29

Pulmonary fibrosis resulting from diverse etiologies is characterized by proliferation of fibroblasts and excessive accumulation of interstitial collagen. Whether fibrosis is associated with selective expansion of fibroblast subpopulations differing in amounts or types of collagens synthesized is unknown. We have previously isolated lines and clones of normal murine lung fibroblasts based on the presence of the Thy 1 surface antigen. These subpopulations differ in morphology, growth characteristics, and display of class II major histocompatibility complex antigens (R.P. Phipps, D.P. Penney, P. Keng, H. Quill, A. Paxhia, S. Derdak, and M. E. Felch. Am. J. Respir. Cell Mol. Biol. 1: 65-74, 1989). We evaluated the amounts and types of collagen and fibronectin synthesized by Thy 1+ (Fib2-T-3+) and Thy 1- (Fib2-T-4-) lung fibroblast lines and clones. Thy 1+ fibroblast line synthesized two- to threefold more collagen and noncollagen protein than the Thy 1- line. In contrast, both the Thy 1+ and Thy 1- lines synthesized similar amounts of fibronectin. Thy 1+ and Thy 1- lines and clones expressed mRNA for alpha 1(I)-and alpha 1(III)-procollagen and synthesized both types (predominantly type I and lesser amounts of type III) of collagen, protein, and mRNA. The fibroblast clones varied significantly in total collagen and fibronectin production, with one Thy 1- clone (D3) synthesizing the largest amount of collagen but relatively little fibronectin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential collagen and fibronectin production by Thy 1+ and Thy 1- lung fibroblast subpopulations. 135 33

The development of bleomycin-induced pulmonary fibrosis in rats was studied over a period of 30 days after an intratracheal instillation of bleomycin. Fibronectin was visualized in histological sections and quantified in bronchoalveolar lavage fluid (BALF) and related to simultaneous measurements of hyaluronan, collagen and albumin in BALF and/or lung tissue extracts. An increase in BALF fibronectin levels was noted after 3 days and the peak value a sixty fold increase was noted at day 7. Thereafter, the fibronectin levels declined and reached control values on day 21. A pronounced, patchily distributed staining for fibronectin appeared in the injured alveolar tissue parallel to the increased lavage fluid fibronectin levels on days 3-7. A fainter, streakily distributed fibronectin staining remained within the alveolar walls in areas with proliferating fibroblasts on days 14-30. Albumin in BALF increased to a peak level, 20 times control values, after 3 days and then rapidly declined. Thus, the ratio of fibronectin to albumin increased to a peak value of 43 times control values on day 7, indicating that plasma leakage cannot be the only source of the observed increase in lavage fibronectin. Lung tissue hydroxyproline increased between days 7 and 30, whereas extractable hyaluronan in lung tissue and bronchoalveolar lavage fluid peaked on days 3-7 and then gradually declined towards normal values on days 21-30. These data demonstrate that fibronectin accumulates in the alveolar tissue during the early inflammatory phase of the bleomycin-induced lung injury, parallelling hyaluronan accumulation and preceding the development of pulmonary fibrosis.
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PMID:Alveolar accumulation of fibronectin and hyaluronan precedes bleomycin-induced pulmonary fibrosis in the rat. 137 89

Pulmonary changes induced in a murine model by intraperitoneal injections of bleomycin were morphologically studied by light and electron microscopy. The number of pulmonary macrophages and the distribution of fibronectin in these cells were evaluated by acid phosphatase and affinity staining using anti-fibronectin horseradish peroxidase conjugates. The onset of acute inflammation occurred 4 days after intraperitoneal injection of bleomycin and reached its peak on the 14th day post-injection. The inflammatory reaction then gradually decreased. Areas of subpleural fibrosis was observed on day 42. On day 14, the ratio of the macrophage in bleomycin-treated mice to that in control mice was 5:1. Many activated and foamy macrophages were observed at that time. These findings indicate that macrophage turnover activity is remarkably increased during the acute inflammatory phase. Fibronectin was detected in the cytoplasm of macrophages on day 14, 21, and 28. It was also detected in both alveolar capillary and epithelial basal lamina as well as in interstitial collagen fibers. On day 42, fibronectin staining was strongly positive in areas of subpleural fibrosis. These results suggest that fibronectin released from pulmonary macrophages plays a role in the process of pulmonary fibrosis.
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PMID:[A morphological study of pulmonary macrophages in bleomycin-injected murine models]. 137 83

The influence of dexamethasone on levels of total fibronectin (tFn), cellular fibronectin (cFn), plasma fibronectin (pFn), and albumin in lung secretions was determined in tracheal aspirate samples collected from 45 infants with bronchopulmonary dysplasia during a 6-week course of dexamethasone therapy. Secretory component for IgA (SC) was used as a reference protein. Thirty-seven infants (82%) survived and had their endotracheal tubes successfully removed. Corticosteroid therapy was associated with a significant decrease in the cFn/SC ratio. There was also a significant decrease in albumin/SC and pFn/SC ratios, suggesting decreased capillary permeability with corticosteroid therapy. Four of the remaining infants did not improve while receiving corticosteroids and died of respiratory failure at 3 to 8 weeks of age. In these "no response" infants, tFn/SC, cFn/SC, pFn/SC, and albumin/SC ratios when corticosteroid therapy was initiated were threefold to fourfold greater (p < 0.01) than ratios in survivors. Another group of four infants initially responded to corticosteroids but subsequently died with severe pulmonary cystic degeneration at 4 to 6 months of age; in these infants, tracheal aspirate tFn/SC, cFn/SC, and albumin/SC ratios were significantly lower than in survivors and remained unchanged during corticosteroid therapy. The decrease in the concentrations of plasma fibronectin and albumin in tracheal aspirate samples from the survivors suggests that the rapid clinical improvement seen in infants with bronchopulmonary dysplasia after the initiation of dexamethasone therapy is due in part to improvement in the integrity of the alveolar-capillary barrier. In addition, the decrease in the aspirate levels of cFn suggests the potential for corticosteroids to limit pulmonary fibrosis in the surviving infants. The depressed levels of fibronectin observed in the infants with severe cystic lung disease may represent an impaired healing response to lung injury.
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PMID:Effect of dexamethasone therapy on fibronectin and albumin levels in lung secretions of infants with bronchopulmonary dysplasia. 140 98

Oxygen-mediated lung injury can stimulate a fibroproliferative response resulting in the alteration of the pulmonary extracellular matrix and subsequent scarring of parenchymal tissue. Fibronectin (FN), a component of the extracellular matrix, appears in increased quantities in fibrotic lung disease. Alveolar macrophages (AMs) are a potential source of this molecule. Using quantitative in situ hybridization, we demonstrated that AMs from rabbits acutely exposed to 100% oxygen (hyperoxia) for up to 64 h have 20-fold greater levels of FN mRNA relative to cells from control animals. When animals were allowed to recover in room air for up to 72 h after maximal oxygen exposure, AM FN mRNA abundance approached baseline levels. Furthermore, in oxygen-exposed animals, the fraction of lavaged cells expressing FN mRNA was increased 10-fold relative to controls. Although there was marked cell-to-cell variation, we conclude that the AM is a potential source of FN in the events leading to hyperoxia-induced pulmonary fibrosis.
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PMID:Increased fibronectin mRNA in alveolar macrophages following in vivo hyperoxia. 141 30

Further investigation is required to delineate the biochemical and cellular interactions that influence lung injury and fibrosis. The results from studies in adults, neonates, and animals suggest that fibronectin may play a key role in the development of pulmonary fibrosis following acute lung injury. Fibronectin as well as other pulmonary cytokines are essential participants in efficient and orderly wound repair; however, the excessive production of these mediators may result in an exaggeration of the normal healing process with the eventual outcome of pulmonary fibrosis. The potential role of fibronectin and other cytokines as mediators and markers of BPD may thus allow for earlier detection and identification of those infants with RDS who are at greatest risk to develop BPD, as well as aiding in the development and selection of therapeutic interventions that can more effectively treat and possibly prevent the deleterious consequences of bronchopulmonary dysplasia.
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PMID:Fibronectin: role in respiratory distress syndrome and bronchopulmonary dysplasia. 151 7

Rats were exposed to saline or cadmium chloride (CdCl2) at 25, 100, or 400 micrograms/kg body weight by intratracheal instillation. At 3, 7, 14, and 28 days after exposure five animals/treatment were euthanized, the lungs were lavaged, and bronchoalveolar lavage fluid (BALF) was analyzed for lactate dehydrogenase (LDH), total protein, N-acetylglucosamindase (NAG), and cell number, type, and viability. Lung hydroxyproline concentration was characterized as a marker of lung collagen. Alveolar macrophages (AM) obtained in BALF were cultured and the release of fibronectin and TNF was determined. Lung tissue was examined microscopically at 28 and 90 days after exposure. Exposure to CdCl2 resulted in lung injury and inflammation demonstrated by increases in BALF LDH, total protein, NAG, and inflammatory cells. AM TNF release was not significantly changed by CdCl2 treatment. All doses of CdCl2 stimulated AM fibronectin secretion, a response which persisted throughout the 28-day postexposure period examined. Pulmonary fibrosis was demonstrated biochemically and/or histologically (trichrome staining tissue) at all CdCl2 dose levels. The association of CdCl2-induced AM fibronectin release with lung fibrosis confirms and extends previous observations relating AM-derived fibronectin to the development of interstitial lung disease and provides further evidence that the persistent increase in AM fibronectin release represents an early indicator of fibrosis.
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PMID:Stimulation of rat alveolar macrophage fibronectin release in a cadmium chloride model of lung injury and fibrosis. 152 50

Studies comparing pulmonary responses to crystalline silica (SiO2) and titanium dioxide (0.3 microns diameter, TiO2-F) demonstrated a positive correlation between alveolar macrophage (AM) release of interleukin-1 (IL-1), tumor necrosis factor (TNF) and fibronectin and, pulmonary granuloma formation, inflammation and fibrosis, respectively. AM IL-1 release was associated with the development of pulmonary granulomas after SiO2 exposure. AM release of TNF positively correlated with the degree of neutrophil recruitment after SiO2 or TiO2-F exposure. A persistent increase in AM fibronectin release consistently correlated with the development of pulmonary fibrosis after SiO2 or TiO2-F exposure. Studies comparing pulmonary responses to ultrafine TiO2 (TiO2-D; particle diameter, 0.02 microns) with TiO2-F demonstrate that ultrafine particles have a relatively greater toxicity on a mass/lung basis. Exposure to TiO2-D resulted in a persistent increase in AM TNF and fibronectin release which was associated with neutrophil recruitment and fibrosis, respectively. TiO2-D did not stimulate AM IL-1 release and this was consistent with the absence of a granulomatous response to TiO2-D. In light of the known bioactivities of IL-1, TNF and fibronectin, these correlative findings suggest that these mediators play significant roles in pulmonary responses to mineral dust exposure and may serve as potential early biomarkers of pulmonary toxicity.
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PMID:Cytokine and growth factor release by alveolar macrophages: potential biomarkers of pulmonary toxicity. 166 54

Fibronectin secreted by macrophages may contribute to the development of pulmonary fibrosis. Prostaglandins are important regulators of macrophage metabolism whose role in the regulation of fibronectin production is not known. In this study, we examined the effects of PGE1 and indomethacin on human monocyte-derived macrophages exposed to these agents in culture for 10 to 14 days. Indomethacin (10 micrograms/ml) reduced the ratio of supernatant fibronectin to adherent cell DNA by 32%, p < 0.01, and reduced lysozyme/DNA by 29%, p < 0.0001. Exogenous PGE1 (1 ng/ml) did not affect fibronectin, but increased lysozyme/DNA by 27%, p < 0.01. In additional experiments, supernatant fibronectin and total protein synthesized in the presence of 3H-leucine were measured. Indomethacin (10 micrograms/ml) had no effect on total supernatant protein radioactivity, but reduced fibronectin/DNA by 33%, p < 0.001, and reduced fibronectin/total protein by 19%, p < 0.01. Since indomethacin increases macrophage secretion of plasminogen activator and interleukin-1, these experiments add to the evidence that specific secretory products of macrophages are regulated independently. We conclude that indomethacin at 10 micrograms/ml decreases the production of fibronectin and lysozyme by monocyte-derived macrophages. The modest size of the effect, and its absence at lower doses of indomethacin, indicate that prostaglandins are unlikely to have a major role in the regulation of macrophage production of fibronectin.
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PMID:Effects of indomethacin and prostaglandin E1 on the production of fibronectin and lysozyme by monocyte-derived macrophages in vitro. 166 50


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