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

The universal features of the histopathology of fibrotic lung disease are derangement of parenchymal collagen and infiltration of the parenchyma with chronic inflammatory cells. To determine if this cellular reaction might be associated with autoimmunity to a consitituent of the alveolar interstitium, peripheral blood lymphocytes were exposed to human type I collagen in vitro and evaluated for the production of migration inhibition factor and cytotoxicity. Data from 18 patients with idiopathic pulmonary fibrosis, 8 patients with pulmonary fibrosis other than idiopathic pulmonary fibrosis, 12 patients with nonfibrotic lung disease, and 9 normals demonstrated that circulating lymphocytes from more than 94% of patients with fibrotic lung disease take part in processes where the recognition of collagen results in migration inhibition factor production and lysis of collagen-coated sheep red blood cells. These collagen-induced cell-mediated phenomena are obviated with human T-lymphocyte antiserum. Collagen-induced migration inhibition factor production and cytotoxicity were found in less than 20% of patients with nonfibrotic disease and were not found in normals. Qualitatively, there was no organ (lung, skin) or species (human, rabbit) collagen specificity in these assays, but human lung alpha 2 chains were recognized more often than alpha 1(I) chains. Circulating lymphocytes from patients with fibrotic disease are present in a normal T to B ratio. These lymphocytes did not incorporate [3H]thymidine when exposed to collagen but did when exposed to T-cell mitogens. These in vitro observations suggest that circulating T-lymphocytes and lung collagen may be intimately associated in the pathogenesis of human fibrotic lung disease.
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PMID:Pathogenic mechanisms in pulmonary fibrosis: collagen-induced migration inhibition factor production and cytotoxicity mediated by lymphocytes. 6 60

Pulmonary fibrosis was induced in eight baboons with bleomycin; five untreated animals were controls. After 45-65 U/kg of bleomycin, lung volumes and diffusing capacity were reduced, and static lung pressure-volume curves were shifted to the right. Right middle lobes were resected at this time in five bleomycin-treated and two control animals. Compared to controls, right middle lobes from bleomycintreated animals had increased weight and contained increased amounts of total protein, collagen, elastin, and DNA; synthesis of collagen and noncollagen protein were also elevated. Occasional alveolar septae were edematous and infiltrated by mononuclear inflammatory cells; a slight increase in collagen was demonstrable histologically. Four of six treated animals died with extensive diffuse interstitial fibrosis after 95 U/kg of bleomycin. Biochemical analyses revealed significantly elevated lobar contents of dry weight, protein, elastin, and collagen. Two animals survived 95 U/kg of bleomycin and were terminated 6 mo after treatment. In these animals, physiologic studies were indicative of restrictive lung disease, but lung histology was nearly normal. Lung weight, total protein, and DNA had returned to control values, but collagen and elastin were increased in amount and concentration. Bleomycin induces an intense inflammatory response in the lung. During this inflammation, connective tissue proliferation occurs in concert with proliferation of other tissue components. Cessation of bleomycin treatment is followed by resolution of inflammation manifested by decreases in tissue mass, cellular content, and nonconnective tissue protein. Collagen and elastin deposited during inflammation are less successfully removed during resolution, leading to a stage characterized by increased concentrations of these proteins. A similar sequence of tissue alterations may occur in idiopathic diffuse interstitial fibrosis of man in response to various lung injuries.
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PMID:Bleomycin-induced diffuse interstitial pulmonary fibrosis in baboons. 7 49

Lung volumes and volume pressure (V-P) relationships were measured in anesthetized hamsters 8, 30, 60, and 90 days after induction of interstitial pulmonary fibrosis by intratracheal administration of bleomycin. Subsequently, total collagen, elastin, protein, deoxyribonucleic acid (DNA), and dry weight were determined in the lungs of each animal. The mean volume of air in the lungs at a transpulmonary pressure of 25 cm H2O and mean quasi-static compliance were decreased at 8 and 30 days and had returned toward normal by 60 and 90 days. Dry lung weight and total protein content were increased at 8 days, peaked at 30 days, and were still greater than normal at 90 days; DNA peaked at 8 days, remained unchanged through day 60, and returned to normal by day 90. Collagen and elastin content, although not significantly different from control at day 8, was increased at day 30 with peak values attained at day 90. Ratios of collagen or elastin to dry weight, total protein, and DNA were decreased at 8 days, normal at 30 days, and increased at 90 days. The ratios of collagen or elastin to total protein, dry lung weight, or DNA cannot be used as indicators of the amounts of these proteins in the whole lung. We conclude that in interstitial pulmonary fibrosis induced with bleomycin the pattern of changing biochemical composition of the lungs cannot be inferred from the lung volumes or V-P relations.
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PMID:Failure of mechanical properties to parallel changes in lung connective tissue composition in bleomycin-induced pulmonary fibrosis in hamsters. 8 16

Cells that possess the morphology and collagen synthetic capacity of fibroblasts were recovered by bronchofiberscopic subsegmental pulmonary lavage from patients with pulmonary fibrosis, from patients with miscellaneous nonfibrotic lung diseases and from healthy volunteers. Lavage cells were placed in tissue culture, observed for 2 to 6 weeks, and compared with human lavage pulmonary alveolar macrophages (PAM), WI-38 and IMR-90 human fetal lung fibroblasts, and adult lung tissue fibroblasts (CLAC-76). Lavage fibroblsts (LF) were identified as proliferating clones in monolayers of nonproliferating PAM and could be subcultured repeatedly. Fibroglasts were propagated from 28 of the 92 lavage specimens cultured. Time-lapse cinematography showed similar distributions of interdivision times for LF, CLAC-76 and WI-38, but the LF and CLAC-76 lines had slower mean migration rates than the fetal line. Light, scanning, and transmission electron microscopy of LF showed attenuated spindle-shaped cells with interdigitating filopodia, flat surfaces with few microvilli, and containing numerous cytoplasmic polyribosomes and rough endoplasmic reticulum. Extracellular fibrils with the appearance of collagen were seen. Collagen synthesis by LF was measured as 3.9% to 4.9% of the cell-associated protein sensitive to bacterial collagenase. This protein was rich in hydroxyproline, and had an electrophoretic migration pattern identical to known collagen. LF did not contain lysozyme although this enzyme was abundant in fresh and 1-week cultured PAM. Thus LF were similar to human fetal and adult lung tissue fibroblasts in their morphology, tissue culture characteristics, constitutive enzymes and collagen synthetic properties but were distinctly different from PAM.
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PMID:Isolation and characterization of fibroblasts obtained by pulmonary lavage of human subjects. 51 Dec 8

Changes in lung structure and collagen metabolism were studied at 1, 2, 3, 4, 6, and 8 weeks in a model of pulmonary fibrosis induced in rats with paraquat plus hyperoxia. Morphologic examination of the lungs revealed that the earliest lesions consisted of severe and irreversible endothelial and alveolar epithelial cell damage. Afterward, an inflammatory process took place, initially dominated by polymorphonuclear leukocytes and then by mononuclear cells, but with the constant presence of granulocytes. From the fourth week on there were fibroblast proliferation and a moderate increase of mast cells. In the early stages alveolitis was focal, but from the second week the lungs were diffusely affected with severe distortion of the architecture. Collagen content was moderately increased in the first 2 weeks and then showed a progressive increment until the end of the experiment. Collagen synthesis was significantly elevated from the fourth week, coinciding with interstitial fibroblast proliferation, although there were some animals that showed increased collagen production from the first week. Collagenolytic activity occurred in 3 stages: at 2 weeks there was increased collagen degradation, at 3, 4, and 6 weeks the values showed a trimodal behavior, and at 8 weeks almost all experimental rats presented an important decrease of collagenolysis. Thus, the development of lung fibrosis was associated first with increased rates of collagen synthesis and later with a decrease of collagen degradation.
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PMID:Experimental pulmonary fibrosis induced by paraquat plus oxygen in rats: a morphologic and biochemical sequential study. 270 80

Collagen accumulation is a major feature of pulmonary fibrosis and other fibrotic lesions. We have studied the synthesis of collagens in fibroblasts cultured from normal and fibrotic human lung specimens and evaluated how it is affected by transforming growth factor-beta (TGF-beta). Fibroblasts were obtained from normal and fibrotic adult human lungs (n = 11; normal = 6, idiopathic pulmonary fibrosis = 5). They were exposed to TGF-beta and pulse-labeled with [3H]proline and [3H]glycine. Collagen production was measured as bacterial collagenase-susceptible radioactivity, and collagen mRNA levels were determined by a solution hybridization assay using labeled procollagen alpha 1[I] cDNA clone HF677 as probe. Synthesis of collagen types I, III, and V were assessed after separating them by DEAE-cellulose chromatography and SDS-polyacrylamide gel electrophoresis. The results showed that both normal and fibrotic lung fibroblasts synthesized similar amounts of collagen. Type I was the major collagen species synthesized by both normal and fibrotic cell types, and the relative proportion of type I, III, and V collagens was similar in both cell types. TGF-beta caused a two to fourfold increase in stimulation of collagen production and collagen mRNA levels, and no differences were detected in the response of normal and fibrotic lung fibroblasts. All collagen types were stimulated by the TGF-beta. TGF-beta did not increase fibroblast proliferation and the majority of normal and fibrotic lung cells exposed to TGF-beta remained in G1 phase of the cell cycle. We conclude that fibroblasts of normal and fibrotic human synthesize similar amounts of collagens.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Collagen synthesis by normal and fibrotic human lung fibroblasts and the effect of transforming growth factor-beta. 275 Nov 76

Silica-induced pulmonary fibrosis is thought to involve fibroblast stimulation by a product of alveolar macrophages (AM) but various cell culture systems have given conflicting results. Macrophage-fibroblast interactions are now studied using an homologous system in which supernatants of rat AM after incubation with silica, are tested on fibroblasts isolated from the same animals to assess the effects on cell proliferation and collagen production. Fibroblast growth varied with initial seeding density and changes induced by AM supernatants varied depending on the proliferative rate. Normal AM supernatants inhibited [3H]-thymidine incorporation into fibroblasts, especially in more rapidly dividing cells. Supernatants of silica-treated AMs also inhibited division of rapidly growing fibroblasts, whereas the same material stimulated growth of slowly dividing cells. Collagen synthesis increased with the length of time that fibroblasts were confluent and was inhibited by control AM supernatants. Silica-treated AM supernatants increased collagen production by fibroblasts confluent for 3 days, whereas the same supernatants inhibited collagen synthesis by cells confluent for at least 8 days. The observation that a factor derived from silica-exposed AM first stimulates them inhibits fibrogenesis, indicates a modulation of the normal macrophage-fibroblast control system. This suggests that other factors may be required in vivo to shift this cellular balance towards the fibrotic process.
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PMID:Modulation of fibroblast activity by normal and silica-exposed alveolar macrophages. 300 67

Analyses of collagen types and their amino acid structures have been made with lungs obtained from eight patients who died from the adult respiratory distress syndrome after non-pulmonary trauma. Collagen in lungs from patients with the adult respiratory distress syndrome was twice as soluble as that in control lungs (p less than 0.01). The proportion of type III collagen in the whole organ as well as in the pepsin solubilised fraction was slightly but significantly raised (net increase of about 5-10% type III collagen (p less than 0.05]. Both type I and type III collagen from the patients contained less hydroxylysine than collagen from control lungs. The alterations in tissue composition described here and observed in normal wound healing support the notion that acute post-traumatic pulmonary fibrosis resembles a wound healing process in the lungs.
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PMID:Pattern of collagen types and molecular structure of collagen in acute post-traumatic pulmonary fibrosis. 342 68

Despite several studies both in vitro and in vivo, the pathogenesis of pulmonary fibrosis is unclear and some findings related to the biochemistry of collagen are controversial. Collagen metabolism was studied in 11 patients with idiopathic pulmonary fibrosis and in six control subjects. There was an increase in collagen concentration (mean 327 (SD 76) compared with control values of 185 (18) micrograms/mg dry weight, p less than 0.001), normal values for biosynthesis (mean 2.2% (0.8%) v 2.08% (0.5%), and a noteworthy decrease in collagenolytic activity (mean 0.07 (0.04) v 0.23 (0.04) micrograms of collagen degraded per mg of collagen incubated, p less than 0.001). These results suggest that an alteration in enzymatic breakdown of collagen plays an important role in the maintenance and progression of interstitial fibrosis in this disease.
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PMID:Concentration, biosynthesis and degradation of collagen in idiopathic pulmonary fibrosis. 375 Feb 41

Fibrosis in the lung is well described histologically. There is destruction of the normal architecture with the appearance of inflammatory cells and connective tissue components, particularly collagen. Biochemical evidence for an increased deposition of collagen in man has been demonstrated in patients with both acute and chronic forms of pulmonary fibrosis. Studies of collagen metabolism in man are equivocal but there is convincing evidence for an increased synthesis rate in animal models of pulmonary fibrosis. Collagen degradation has been little studied but may be important, given the recent evidence indicating quite rapid turnover of lung collagen and a decreased degradation of collagen in experimental disease. The distribution of collagen types has been studied in man, where there is some evidence for the production of type III collagen in the early active phase of disease with a preponderance of type I collagen in the late stages. The cellular mechanisms leading to these changes are uncertain but the alveolar macrophage may play a central role, since it is capable of releasing factors which expand the fibroblast population as well as attracting new fibroblasts to the site of injury. These pathways are described for what is essentially the normal physiological response of scar formation, which has pathological consequences in the lung, a tissue requiring thin membranes at its epithelial and endothelial surfaces, in order to perform its main function of gas exchange.
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PMID:Biochemical pathways leading to collagen deposition in pulmonary fibrosis. 385 24


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