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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 is an irreversible accumulation of connective tissue in the interstitium of the lung. The pathogenesis of pulmonary fibrosis is not well understood. Research on animal models and studies of human lung disease suggest the initiating events may be a combination of pulmonary injury and the recruitment of inflammatory cells, mainly macrophages. A number of well characterized cytokines, including TGF-beta, have been either found in the injured lung or produced by inflammatory cells removed from the lung. In an animal model of pulmonary fibrosis, TGF-beta production is increased prior to collagen synthesis and is mainly produced by alveolar macrophages. In advanced idiopathic pulmonary fibrosis, a human fibrotic lung disease, extensive TGF-beta deposition can be detected by immunohistochemical staining, primarily in epithelial cells in areas of lung regeneration and remodelling. This suggests that the pathogenesis of the progressive fibrosis characteristic of this lung disease may be an aberrant repair process.
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PMID:The role of TGF-beta in pulmonary fibrosis. 171 97

A major role of TNF in pulmonary fibrosis is supported by the following evidences obtained from pulmonary fibrosis induced in mice by bleomycin or silica particles; 1) these diseases are associated with a marked and lasting increase of the TNF mRNA within the lung, 2) they can be prevented by a treatment with anti TNF antibody or aggravated by a perfusion of mouse recombinant TNF, 3) an infusion of TNF-alpha can reproduce the alterations observed during pulmonary fibrosis such as growth of fibroblasts, collagen deposition, cell necrosis.
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PMID:Is "tumor necrosis factor" the major effector of pulmonary fibrosis? 171 90

Oxidant-mediated epithelial injury and repair processes may promote the development of pulmonary fibrosis. The authors examined this hypothesis by inducing oxidant injury in hamsters with intratracheally instilled mixtures of glucose, glucose oxidase (GO) and lactoperoxidase at weekly intervals. Solutions containing denatured GO (DE) served as a control treatment. One and six days after each treatment, anesthetized animals were sacrificed and lavaged, and their lungs and plasma were preserved for further study. Although DE-treatment consistently evoked a transient, neutrophil-rich inflammatory response, no significant biochemical or morphologic changes were detected at the ensuing 6-day time points. In contrast, repeated GO treatments prolonged inflammation and injured the alveolar epithelium, evidenced by significantly greater levels of neutrophils and macrophages in bronchoalveolar lavage fluid (BALF) and increased BALF levels of protein, beta-glucuronidase and lactic dehydrogenase activities. Active GO also altered BALF lymphocytes and monocytes, but no discernable pattern emerged. Fibrotic, consolidated parenchyma appeared after the second and third GO exposures, coinciding with increased levels of total collagen, prolyl hydroxylase activity, and anti-oxidant enzyme activities. Although alveolitis and type II cell hyperplasia were observed after the initial treatment, polyplike nodules covered by hyperplastic, undifferentiated epithelium were evident after the third treatment. After each exposure, GO-treated animals had larger volumes of parenchymal lesion than DE-treated hamsters. These data indicate that normal alveolar epithelial repair processes were greatly disrupted by repeated oxidant injury and suggest that repeated and/or continued epithelial injury may contribute to the development of pulmonary fibrosis.
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PMID:Repeated exposures to enzyme-generated oxidants cause alveolitis, epithelial hyperplasia, and fibrosis in hamsters. 175 May 14

Pulmonary fibrosis in response to silica or asbestos has been attributed to secretion of fibroblast growth factors (FGF) by alveolar macrophages (AM). However, since fibrosis is interstitial, and is associated with particle retention by interstitial macrophages (IM), we have now compared the secretory activity of FGF by rat alveolar (AM) and IM in response to silica and to long or short asbestos fibers. AM were obtained by bronchoalveolar lavage, and IM by collecting macrophages that migrate from explants of a previously lavaged and perfused lung. Six weeks after instilling silica, isolated AM and IM from lungs secreted equal amounts of FGF. Six weeks after instilling short asbestos fibers in vivo, lavaged AM secreted FGF, but there was no change in fibroblast growth and no fibrosis in vivo. After long fibers, that reach the interstitium were instilled, isolated IM secreted FGF, and collagen levels were increased. When IM and AM were isolated from normal rats and exposed to the same silica or asbestos samples in vitro, it was found that all macrophage supernatants contained FGF, and the response of AM and IM was equal. The results indicate that the two macrophage populations respond equally to particles with respect to FGF secretion. The greater fibrotic reaction seen in vivo may be explained by the proximity of fibroblasts to particle-laden macrophages within the interstitium allowing more efficient transfer of FGF.
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PMID:Comparison of alveolar and interstitial macrophages in fibroblast stimulation after silica and long or short asbestos. 184 33

Intralobar instillation of cadmium chloride (CdCl2) into the left lungs of rats initiated a sequence of events that culminated in massive unilateral intraluminal fibrosis. Early events (days 1 and 2) after CdCl2 administration included infiltration of the treated lung with polymorphonuclear leukocytes, an increase in the number of alveolar macrophages, activation of the macrophages as assessed by the induction of cathepsin L mRNA, and the induction in liver of mRNA for the acute-phase response protein, alpha 1-acid glycoprotein. By days 5 to 7 in the treated lungs, mRNA for procollagen alpha 1(I) increased 20- to 60-fold, and mRNA for procollagen alpha 1(III) increased 4- to 14-fold. These increases were correlated with the almost complete filling of the alveolar spaces with fibroblasts and collagen. The contralateral lung exhibited no significant change in histology but showed a similar induction of collagen gene expression. These increases were tissue-specific, as the livers of these animals showed no change from the control levels of collagen gene expression. Procollagen messages in the treated and contralateral lungs were equally competent for translation into pro-alpha 1(I) and pro-alpha 2(I) polypeptides. Both the treated and contralateral lungs increased hydroxyproline content about 1.5- to 2-fold over 14 days. The contralateral lung, but not the treated lung, showed a 2-fold increase in lung volume. As a result, the collagen density (mg collagen/ml lung volume) doubled in the treated lung but remained constant in the contralateral lung. These data indicate that CdCl2 caused a rapid induction of pulmonary fibrosis in the treated lungs of rats and stimulated histologically normal growth of the contralateral lung.
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PMID:Induction of unilateral pulmonary fibrosis in the rat by cadmium chloride. 191 Aug 23

Determinants of pulmonary fibrosis induced by inhaled mineral dusts include quantity retained, particle size, and surface area, together with their physical form and the reactive surface groups presented to alveolar cells. The outstanding problem is to ascertain how these factors exert their deleterious effects. Both compact and fibrous minerals inflict membrane damage, for which chemical mechanisms still leave uncertainty. A major weakness of cytotoxicity studies, even when lipid peroxidation and reactive oxygen species are considered, lies in tacitly assuming that membrane damage suffices to account for fibrogenesis, whereas the parallel occurrence of such manifestations does not necessarily imply causation. The two-phase procedure established that particles, both compact and fibrous, induce release of a macrophage factor that provokes fibroblasts into collagen synthesis. The amino acid composition of the macrophage fibrogenic factor was characterized and its intracellular action explained. Fibrous particles introduce complexities respecting type, durability, and dimensions. Asbestotic fibrosis is believed to depend on long fibers, but scrutiny of the evidence from experimental and human sources reveals that a role for short fibers needs to be entertained. Using the two-phase system, short fibers proved fibrogenic. Other mechanisms, agonistic and antagonistic, may participate. Growth factors may affect the fibroblast population and collagen production, with cytokines such as interleukin-1 and tumor necrosis factor exerting control. Immune involvement is best regarded as an epiphenomenon. Downregulation of fibrogenesis may follow collagenase release from macrophages and fibroblasts, while augmented type II cell secretion of lipid can interfere with the macrophage-particle reaction.
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PMID:Minerals, fibrosis, and the lung. 195 26

The purpose of this investigation was to determine whether subpopulations of murine lung fibroblasts produced interleukin 1 (IL 1). We previously identified two major populations of pulmonary fibroblasts based on the presence or absence of Thy-1. Thy-1+ and Thy-1- subsets synthesize fibronectin and type I and III collagen, but only the Thy-1- population displays class II major histocompatibility complex antigens after stimulation with interferon-gamma and presents antigen to T helper clones. Interestingly, in the current study we determined that only Thy-1- fibroblast lines and clones synthesized IL 1. Although constitutive production was low, tumor necrosis factor -alpha (TNF-alpha) stimulated 5-20-fold increases in IL 1 production in Thy-1- fibroblasts. The Thy-1+ fibroblasts did not produce IL 1 even after TNF-alpha treatment. Northern blot analysis of TNF-alpha treated cells revealed that in the Thy-1- subset increased mRNA levels for IL 1 alpha were detected, while IL 1 beta mRNA was not detected. Furthermore, IL 1 activity from TNF-alpha-treated Thy-1- fibroblast membranes and supernatants was completely neutralized by IL 1 alpha-specific antibodies. These observations support the hypothesis that the antigen-presenting Thy-1- subset is important for promoting the inflammation associated with pulmonary fibrosis. In addition, the existence of functional subsets of lung fibroblasts is further substantiated by differential expression of IL 1.
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PMID:Differential expression of interleukin 1 alpha by Thy-1+ and Thy-1- lung fibroblast subpopulations: enhancement of interleukin 1 alpha production by tumor necrosis factor-alpha. 197 21

Amiodarone is a Class III antiarrhythmic agent that has been implicated as a cause of human pulmonary fibrosis. Pulmonary fibrosis is associated with increased levels of connective tissue proteins such as collagen and elastin. The purpose of this investigation was to determine whether elastin synthesis would be altered by in vitro amiodarone administration. Primary hamster lung cell cultures were utilized. Cultures were treated with 2, 10, and 20 micrograms/ml amiodarone. Following treatment, elastin synthesis was monitored by a biochemical tracer assay based on the presence of the cross-linking amino acids: desmosine/isodesmosine. These cross-links are found only in elastin. Addition of [14C] lysine to cultures results in uptake of the radiolabel into the cross-links. Cross-links were isolated and identified using chromatography and electrophoresis. At all doses of amiodarone, elastin synthesis was seen to increase above control levels. Light and electron microscopy confirmed the presence of an extracellular matrix. The morphologic studies also revealed the presence of cytoplasmic inclusion bodies and vacuoles that are often associated with cationic, amphiphilic drugs such as amiodarone.
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PMID:Effects of amiodarone on elastin biosynthesis in primary hamster lung cell cultures. 200 41

The synthesis of collagen and EIIIA-containing cellular fibronectin in certain forms of pulmonary fibrosis occurs in discrete locations: in the Masson bodies in bronchiolitis obliterans with organizing pneumonia and in focal clusters of fibroblasts (fibroblastic foci) within airspaces in usual interstitial pneumonia. These sites were examined by electron microscopy and immunohistochemistry using antibodies against cytoskeletal markers and extracellular matrix components in biopsies from three patients with bronchiolitis obliterans with organizing pneumonia and four patients with usual interstitial pneumonia. Fibroblasts of both Masson bodies and fibroblastic foci expressed vimentin and alpha smooth muscle actin but not desmin, distinguishing them from true smooth muscle. In both structures fibroblasts with well-formed actin filament bundles were aligned parallel to one another, enmeshed in a matrix of fibronectin-containing fibrils (microtendons) that linked cells and collagen bundles. Similar features characterize the phase of contraction during the healing of skin wounds. This suggests that active contractions of fibroblasts plays a role in the remodeling of the lung in pulmonary fibrosis.
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PMID:The roles of the myofibroblast in idiopathic pulmonary fibrosis. Ultrastructural and immunohistochemical features of sites of active extracellular matrix synthesis. 202 10

The clinician confronted to the diagnosis of infiltrative lung disease has to consider a wide spectrum of aetiologies. Among them, diffuse fibrosing interstitial lung disease is characterized by the deposition of collagen within alveolar structures. Either acute alveolar injury or chronic inflammatory alveolitis can induce pulmonary fibrosis. Basic research investigates the cells, the cytokines, and the extracellular matrix involved in the perpetuation of the fibropoliferative process.
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PMID:[Diffuse infiltrative lung diseases and fibrosis]. 206 14


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