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PubMed1999

Systemic and pulmonary oxidative stress in idiopathic pulmonary fibrosis.

An oxidant/antioxidant imbalance has been proposed in patients with idiopathic pulmonary fibrosis (IPF). We tested this hypothesis by measuring various parameters of the oxidant/antioxidant balance in the plasma of 12 patients with IPF (7 nonsmokers and 5 smokers); in the bronchoalveolar lavage fluid (BALF) of 24 patients with IPF (17 nonsmokers and 7 smokers) and 31 healthy subjects (23 nonsmokers and 8 smokers). The trolox equivalent antioxidant capacity (TEAC) in plasma and BALF was lower in nonsmoking patients with IPF (plasma 0.55+/-0.1 mM, p<.001; BALF 4.8+/-1.2 microM, mean +/-SEM, p<.01), compared with healthy nonsmokers (plasma 1.33+/-0.03 mM; BALF 10+/-2 microM). Similar trends in plasma and BALF TEAC were observed in smoking patients with IPF in comparison with healthy smokers. The decrease in BALF TEAC was concomitant with a decrease in BALF protein thiol levels, but the decrease TEAC levels in plasma in IPF patients was not accompanied by a decrease in protein thiol levels. Reduced glutathione (GSH) was lower in BALF in nonsmoking patients with IPF (1.0+/-0.1 microM) compared with healthy nonsmokers (2.3+/-0.2 microM, p<.001). In contrast, GSH levels were higher in smoking patients with IPF (5.2+/-1.1 microM, p<.001) than in nonsmoking patients. GSSG levels were not different in any of the groups. The levels of products of lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS) in plasma and BALF were significantly increased in both smoking (plasma 2.2+/-0.5 microM, p<.01; BALF 0.18+/-0.04 microM, p<.001), and nonsmoking (plasma 2.1+/-0.3 microM, p<.01; BALF 0.22+/-0.05 microM, p<.001) IPF patients, compared with healthy nonsmokers (plasma 1.4+/-0.3 microM; BALF 0.05+/-0.004 microM). These data show evidence of oxidant/antioxidant imbalance in the lungs of patients with IPF, which is also reflected as systemic oxidant stress.

Bronchoalveolar Lavage Fluid↗

PubMed1981

Mechanisms of neutrophil accumulation in the lungs of patients with idiopathic pulmonary fibrosis.

Neutrophils are a characteristic feature of the alveolitis of idiopathic pulmonary fibrosis (IPF). a chronic disorder limited to lung. One mechanism by which neutrophils may be selectively attracted to lung and not other tissues is via the secretion of the neutrophil-specific chemotactic factor by alveolar macrophages. To evaluate the role of alveolar macrophages in modulating the migration of neutrophils to he lung in IPF, alveolar macrophages, obtained by bronchoalveolar lavage of patients with IPF, were evaluated for their ability to release a chemotactic factor for neutrophils. Unstimulated alveolar macrophages from normal individuals did not release the factor. In patients with IPF, there was a significant correlation between the proportions of neutrophils in lavage fluid and the release of a chemotactic factor for neutrophils by alveolar macrophages (p less than 0.001). The chemotactic factor released by IPF alveolar macrophages was of low molecular weight (400-600), at least partially lipid in nature, and preferentially attracted neutrophils compared with monocytes. Several lines of evidence suggested that immune complexes in the lung stimulated alveolar macrophages of patients with IPF to release the chemotactic factor. First, immune complexes stimulated normal macrophages to release the factor.Second, there was a significant correlation between the release of the chemotactic factor by IPF alveolar macrophages and the levels of immune complexes in bronchoalveolar lavage fluid. Third, bronchoalveolar lavage fluid containing immune complexes stimulated normal macrophages to release the factor. Fourth, IPF alveolar macrophages that released large amounts of the chemotactic factor had an apparent suppression of their immunoglobulin (Ig)G Fc receptor function, suggesting that immune complexes were bound to their surface. In contrast, the IgG Fc receptor function of IPF alveolar macrophages that released only small amounts of the factor was similar to that of normal macrophages. These studies suggest that neutrophils are attracted to the lung in patients with IPF by a potent chemotactic factor released by alveolar macrophages that have been stimulated, in vivo, via their IgG Fc receptor by immune complexes.

Adult↗

PubMed2005

Animal models of pulmonary fibrosis.

In general, there are two types of animal models: natural and experimental. Because there are no natural models for pulmonary fibrosis, an experimental model that reproduces key aspects of the human disease would be useful for the study of this form of lung disease, the natural history of which is not always known. To date, a variety of animal models have been used to investigate mechanisms of pulmonary and other types of fibrosis, including the intratracheal instillation of bleomycin, fluorescein isothiocyanate, or particulate matter, such as silica and asbestos. This chapter will describe two commonly used techniques, namely bleomycin and silica-induced, which have been developed for the study of pulmonary fibrosis in animal models.

Anesthetics↗

PubMed1999

Idiopathic pulmonary fibrosis in a Staffordshire bull terrier with hypothyroidism.

Radiographic evidence of chronic interstitial lung changes, usually believed to be attributable to lung fibrosis, is readily recognised in canine practice. Furthermore, there is a body of anecdotal evidence suggesting that a specific clinical entity consistent with chronic lung fibrosis occurs in specific breeds of terrier dogs. However, there is little pathological data to confirm these radiographic and clinical findings and, therefore, chronic interstitial lung disease of dogs is poorly characterised. In this report, a case of chronic pulmonary fibrosis is described in which histopathological confirmation was possible, and suggested that the condition might be analogous to idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) in humans.

Animals↗

PubMed2003

Upper lobe pulmonary fibrosis associated with high-dose chemotherapy containing BCNU for bone marrow transplantation.

Upper lobe fibrotic lung disease is most often associated with sarcoidosis, Langerhans cell histiocytosis, silicosis, and other pneumoconioses but is usually not associated with drug-induced lung disease. Carmustine (BCNU) is a chemotherapeutic agent known to cause pulmonary toxicity. The radiographic pattern is usually diffuse bilateral lung disease predominantly in the lung bases. Upper lobe fibrotic disease associated with BCNU has been reported to occur in children treated for central nervous system gliomas. Often the lung disease occurs years after the exposure. Despite the widespread use of BCNU in the treatment of malignancy in adults, to our knowledge, the complication of upper lobe fibrotic disease has not been reported in adults. We describe a patient who presented with pneumothorax and bilateral upper lobe pulmonary fibrosis that we believe was due to BCNU given for bone marrow transplantation as part of therapy for breast cancer. Bilateral upper lobe pulmonary fibrosis can be associated with chemotherapeutic drugs.

Antineoplastic Agents, Alkylating↗

PubMed1992

Lung function and radiographic signs of pulmonary fibrosis in oil exposed workers in a cable manufacturing company: a follow up study.

Thirty seven workers employed for at least three years in oil impregnation of cables during 1963-83 were followed up in 1990 to study the development of pulmonary fibrosis and consequences for lung function. They had been exposed to concentrations of mineral oil vapours of 50-100 mg/m3, and concentrations of oil mist of 0.5-1.5 mg/m3. All 29 living persons were traced. For each person one control matched for age, height, and smoking habits was selected. Among 25 workers followed up with radiographic studies, 10 cases of pulmonary fibrosis were found, by contrast with one case in the control group (p less than 0.01). Chest radiographs from 1979-80 and 1989-90 were reviewed. The profusion of small opacities increased in seven of 16 persons during 10 years without exposure. Seventeen workers had lung function tests. The bellows function (VC, FEV1, MVV) and lung volumes (TLC, RV) did not differ from those in the matched controls (p greater than 0.05), but the carbon monoxide transfer factor (TLCO) was decreased. The largest reduction of TLCO (1.5 mmol/kPa/min) was found among workers exposed for 10 years or more (p less than 0.05). Arterial blood gases were not affected at rest, but during maximum tread mill exercise, PO2 and HbO2 were reduced in exposed workers compared with controls, particularly among those exposed for at least 10 years (p less than 0.05). Exposure to low viscosity oil mist and vapour is the most plausible cause of the fibrosis. Unaffected bellows function, reduced TLCO, and decreased arterial blood oxygen during exercise is compatible with peribronchiolar fibrosis.

Adult↗

PubMed2006

[STAT1 antisense oligonucleotides inhibit secretion of TNF-alpha, IL-8 and NO in alveolar macrophages of rats suffering from interstitial pulmonary fibrosis].

AIM: To investigate the effect of signal transducer and activator of transcription 1 (STAT1) antisense oligonucleotides (ASON) on secretion of TNF-alpha, IL-8 and NO by alveolar macrophages (AMs) of rats with bleomycin (BLM)-induced pulmonary fibrosis. METHODS: Five adult female Wistar rats were intratracheally instilled with BLM. After 7 days, the rats were sacrificed under ketamine anaesthesia and bronchoalveolar lavage (BAL) was performed to obtain AMs. AMs were divided into four groups: STAT1 ASON, STAT1 sense oligonucleotides (SON), dexamethasone (DEX) and control groups. Culture medium was collected at 36 hours after adding STAT1 ASON, STAT1 SON and DEX, respectively. The concentrations of TNF-alpha, IL-8 and NO in the culture medium were detected. RESULTS: The concentrations of TNF-alpha, IL-8 and NO in STAT1 ASON group were lower than those in STAT1 SON, DEX and control groups (P<0.05). Moreover, the concentrations of TNF-alpha, IL-8 and NO in DEX group were also lower than those in control and STAT1 SON groups (P<0.05). But compared with control group, the concentrations of TNF-alpha, IL-8 and NO in STAT1 SON group was not significantly different (P<0.05). CONCLUSION: STAT1 ASON can inhibit the secretion of TNF-alpha, IL-8 and NO in AMs. STAT1 may become a target for treating pulmonary fibrosis.

Animals↗

PubMed2003

Lung cancer associated with diffuse pulmonary fibrosis: CT-pathologic correlation.

The authors reviewed the computed tomographic (CT) scans and pathologic specimens of 57 histologically proved bronchogenic carcinomas (35 squamous cell carcinomas, 12 small cell carcinomas, and 10 adenocarcinomas) in 47 patients with diffuse pulmonary fibrosis. The patients ranged in age from 61 to 87 years (mean age, 72 years; 42 men and 5 women). On radiography and CT, most tumors (82%) were located in peripheral areas of honeycomb lung. In 50 of the 57 lesions, the tumors were round or lobulated with sharp margins. In seven tumors, including six squamous cell carcinomas and one small cell carcinoma, the tumor invaded the adjacent honeycomb lung and lacked distinct margins. Intratumor lucency was seen in 13 tumors (five solitary and eight multiple). The CT findings, including high-resolution CT scans, were compared with the histologic findings in a subgroup of 29 lesions in 25 patients with available surgical or autopsy specimens. Invasive growth of tumors with unclear margins (four lesions), septal thickening of the contiguous/surrounding honeycombed areas (16 lesions), and discrete masses (nine lesions) with solitary (four of nine) or multiple (five of nine) intratumor lucencies. The lucencies in six of nine patients (67%) with intratumor lucencies were found to represent engulfed cystic airspaces histologically. CT revealed that bronchogenic carcinoma associated with diffuse pulmonary fibrosis has distinct morphologic characteristics that correlate histologically with a specific pattern of tumor growth.

Aged↗

PubMed2004

The influence of dexamethasone on the proliferation and apoptosis of pulmonary inflammatory cells in bleomycin-induced pulmonary fibrosis in rats.

OBJECTIVE: The aim of this study was to investigate the inhibitory effect of dexamethasone on the state of proliferation/apoptosis of the pulmonary inflammatory cells in a rat pulmonary fibrosis model induced by bleomycin. METHODOLOGY: Seventy-five pathogen-free Sprague-Dawley (SD) rats were randomly divided into three groups: control, bleomycin (BLM) and dexamethasone (DXM) groups with 25 rats in each group. Each group was then divided into five subgroups based on time of study (1-, 3-, 7-, 14- and 28-days). BAL fluid was obtained, the cells were counted and a differential was performed. A lower DNA content in apoptotic cells was detected and quantitated by flow cytometry. Haematoxylin and eosin staining was performed to observe the extent of alveolitis and fibrosis of lung tissue; the morphological changes in apoptotic cells were discerned by transmission electron-microscopy and a semi-quantitative assessment of apoptotic cells in lung tissue was performed using in situ TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabelling). RESULTS: The total number of inflammatory cells and the percentage of neutrophils in BAL fluid in almost every subgroup of the DXM group were significantly lower than those in corresponding subgroups of the BLM group (P < 0.01). The percentages of apoptotic cells in BAL fluid in the 14-day and 28-day subgroups of the DXM group were higher than those in corresponding subgroups of the BLM group (P < 0.05). The peak of alveolitis in the DXM group shifted backward and the extent of fibrosis was less than that in the BLM group. The apoptosis index (AI) of inflammatory cells in each of the DXM subgroups was higher than that in corresponding BLM subgroups except for day 14. CONCLUSION: Dexamethasone can induce apoptosis of pulmonary inflammatory cells and reduce the extent of alveolitis and fibrosis in bleomycin-induced pulmonary fibrosis of rats.

Animals↗

PubMed2004

Factors associated with early-stage pulmonary fibrosis as determined by high-resolution computed tomography among persons occupationally exposed to asbestos.

OBJECTIVES: Asbestosis remains difficult to diagnose, particularly in its early stages. The aim of this study was to determine criteria for independently associated features of pulmonary fibrosis in high-resolution computed tomograms among persons occupationally exposed to asbestos. METHODS: Retired persons with documented occupational asbestos exposure and no known asbestos-related diseases were assessed for occupational, clinical, functional respiratory, and chest X-ray criteria. In addition, they all underwent high-resolution computed tomography (HRCT) in the prone position. RESULTS: Altogether 51 (7.2%) of the 706 enrolled participants had features of pulmonary fibrosis consistent with asbestosis in the HRCT. Among those with small irregular opacities of <1/0 according to the 1980 International Labour Office Classification (ILO-C) in their X-rays, 5% had asbestosis in the HRCT. In a multivariate analysis, only age [odds ratio (OR) per year 1.08, 95% confidence interval (95% CI) 1.02-1.14], cumulative-exposure index (CEI) for asbestos (OR 6.4, 95% CI 1.5-28.4 for a CEI of > or =100 fibers/ml x years), and the presence of small irregular X-ray opacities of > or =1/0 ILO-C (OR 3.0, 95% CI 1.6-6.0) were independently associated with HRCT asbestosis. No combinations of these criteria simultaneously yielded high sensitivity and specificity for the diagnosis of early-stage HRCT asbestosis. Moreover, only 2% of the persons with a CEI of <25 fibers/ml x years had HRCT asbestosis, the finding confirming the low incidence of asbestosis for such low exposure, as previously reported on the basis of X-ray data. CONCLUSIONS: Additional research is needed to better identify the persons most likely to benefit from HRCT screening for asbestosis.

Aged↗

PubMed1999

Expression of transforming growth factor-beta1 and tumour necrosis factor-alpha in bronchoalveolar lavage cells in murine pulmonary fibrosis after intraperitoneal administration of bleomycin.

OBJECTIVE: We previously observed increased expression of interleukin-1beta, platelet-derived growth factor-A, and insulin-like growth factor-I in bronchoalveolar lavage (BAL) cells during the development of pulmonary fibrosis after an intraperitoneal administration of bleomycin in mice. The purpose of this study was to investigate the roles of tumour necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta1 in this model. METHODOLOGY: We investigated the mRNA expression levels of TNF-alpha and TGF-beta1 in BAL cells of Institute for Cancer Research mice after 10 days of the intraperitoneal administration of bleomycin with or without treatment with a specific neutrophil elastase inhibitor, ONO-5046 x Na. RESULTS: On day 1 but not on days 15 and 29, the relative amount of TGF-beta1 mRNA in the bleomycin-treated mice was significantly decreased compared with control mice. In the mice treated with both bleomycin and ONO-5046 x Na intermediate values for TGF-beta1 were obtained. No significant differences in TNF-alpha expression were observed in any of the treatment groups. CONCLUSIONS: These results suggest that a reduced expression of TGF-beta1 in BAL cells in the early phase may be important during the development of murine pulmonary fibrosis induced by an intraperitoneal administration of bleomycin.

Animals↗

PubMed1995

Fatal pulmonary fibrosis complicating low dose methotrexate therapy for rheumatoid arthritis.

We report the fatal disease course of 2 aged patients with rheumatoid arthritis (RA). Both had respiratory complaints after 10-15 weeks of treatment with methotrexate (MTX). After withdrawal of MTX, and despite the use of corticosteroids and ventilatory support, both died of respiratory failure. Post mortem examination showed extensive pulmonary fibrosis, bronchiolitis obliterans, and hyperplasia of type II pneumocytes. To our knowledge, this is the first report of fatal pulmonary fibrosis following short courses of low dose MTX therapy for RA.

Aged↗

PubMed2002

BALF N-acetylglucosaminidase and beta-galactosidase activities in idiopathic pulmonary fibrosis.

The lysosomal enzymes N-acetylglucosaminidase (N-ACGA) and beta-galactosidase (beta-gal) are involved in cellular collagen metabolism and may, therefore, be markers of fibrosis in idiopathic interstitial pneumonias, such as idiopathic pulmonary fibrosis (IPF). N-ACGA and beta-gal were analyzed in the bronchoalveolar lavage fluid (BALF) of patients with the histologic pattern of usual interstitial pneumonia (UIP, n=10) and controls (n=9). Cellular distribution in BALF as well as the concentration of TGF-beta a well-known mediator of fibroblast matrix deposition were correlated to the enzyme activities in both groups of patients. We found that both, N-ACGA (UIP: 25.2 nmol/l s +/- 3.4; controls: 73 nmol/l s +/- 1.3) and beta-gal (UIP: 4.7 nmol/l s +/- 0.5; controls: 2.4 nmol/l s +/- 0.3) were elevated significantly in BALF of patients with IPF compared to that of control patients (P<0.003). This increase was paralleled by an increase in neutrophils (IPF: 17.9% +/- 21.8; controls: 5.4% +/- 6.3; P=0.03) and eosinophils (IPF: 2.0% +/- 1.5; controls: 0.2% +/- 0.45; P=0.002) in BALF fluid. In addition, N-ACGA activity correlated closely with lung function (FVC, TLC, and DLCO), transforming growth factor-beta (TGF-beta) in BALF (r=0.77, P=0.008) and activated lymphocytes (r=0.66, P=0.0021). Our findings suggest that measurement of lysosomal enzymes such as N-ACGA may represent a useful indicator of fibrotic activity in IPF.

Acetylglucosaminidase↗

PubMed1997

Thrombin stimulates platelet-derived growth factor release by alveolar macrophages in rats--significance in bleomycin-induced pulmonary fibrosis.

Thrombin is a multifunctional enzyme generated at sites of vascular injury, and is known to be increased in the lungs in some types of fibrotic lung disease. In this study, to determine whether thrombin is associated with fibroblast growth and pulmonary fibrosis in these disorders, we examined whether a growth factor for fibroblasts (platelet-derived growth factor, PDGF) was released by thrombin-stimulated alveolar macrophages (AM). The culture supernatants of rat AM stimulated with 1 or 10 U/ml of thrombin showed a significant increase in fibroblast growth-stimulating activity (FGA). Pretreatment of the AM supernatant with anti-PDGF-AA antibody significantly decreased the FGA, but pretreatment with anti-PDGF-BB antibody did not. The supernatants of AM stimulated with thrombin also increased the growth of fibroblasts from the lungs of rats with bleomycin-induced lung injury. These results indicate that thrombin stimulates AM to release PDGF-AA, which is responsible, at least in part, for fibroblast growth and the development of pulmonary fibrosis in some types of fibrotic lung disease.

Animals↗

PubMed2000

Pulmonary function and high-resolution CT findings in patients with an inherited form of pulmonary fibrosis, Hermansky-Pudlak syndrome, due to mutations in HPS-1.

OBJECTIVE: To describe and correlate pulmonary function and high-resolution CT (HRCT) scan scores in individuals with a high risk for development of pulmonary fibrosis, ie, Hermansky-Pudlak syndrome (HPS) patients with mutations in the HPS-1 gene. DESIGN: Cross-sectional analysis of consecutive, eligible patients. PATIENTS: Thirty-eight HPS inpatients at the National Institutes of Health Clinical Center with HPS-1 mutations. RESULTS: Thirty-seven patients were Puerto Rican and exhibited the typical 16-base pair (bp) duplication in exon 15 of HPS-1. One non-Puerto Rican was homozygous for a different mutation (intervening sequence 17 -2 A-->C) previously reported in the HPS-1 gene; he died at age 35 of pulmonary insufficiency. For the 23 patients who had pulmonary symptoms, the mean age of onset was 35 years. For all 38 patients (mean age, 37 +/- 2 years), the mean FVC was 71% of predicted; the mean FEV(1), 76%; mean total lung capacity (TLC), 72%; mean vital capacity (VC), 68%; and mean diffusing capacity of the lung for carbon monoxide (DLCO), 72%. When patients were grouped according to the extent of their reduction in FVC, the other four pulmonary function parameters followed the FVC. Seventeen patients had abnormal chest radiographs, and 31 (82%) had abnormal HRCT scans of the chest, for which a scoring system of 0 (normal) to 3 (severe fibrosis) is presented. The mean +/- SEM HRCT score for 38 patients was 1.30 +/- 0.17. HRCT scores correlated inversely with FVC and DLCO. CONCLUSIONS: Mutations in the HPS-1 gene, whether or not they involve the typical 16-bp duplication seen in Puerto Rican patients, are associated with fatal pulmonary fibrosis. In affected patients, the FVC, FEV(1), TLC, VC, and DLCO fall in concert, and this functional deficit correlates with HRCT scan evidence of progression of interstitial lung disease.

Adult↗

PubMed1996

Gallium-67 scanning for detection of alveolitis in idiopathic pulmonary fibrosis and sarcoidosis.

OBJECTIVE: To investigate 67Gallium scanning for the detection of alveolitis in idiopathic pulmonary fibrosis and sarcoidosis. PATIENTS AND METHODS: 67Ga scintigraphy was performed in 14 patients with IPF (age: mean +/- s = 58.3 +/- 10.3 years), 13 patients with sarcoidosis (age: mean +/- s = 46.9 +/- 9.0 years) and 11 controls (age: mean +/- s = 44.0 +/- 10.5 years). RESULTS: Lung/thigh ratio was respectively 3.18 +/- 0.07 in IPF, 3.12 +/- 0.94 in sarcoidosis and 2.11 +/- 0.26 in controls. IPF and sarcoidosis groups had a significantly higher lung/thigh ratio comparing with the control group (P < 0.05). Three patients received 67Ga scanning examination after corticosteroid therapy and the 67Ga uptake decreased. CONCLUSIONS: The 67Ga scintigraphy is useful in monitoring the activity and extent of alveolitis.

Aged↗

PubMed1999

Transforming growth factor-alpha deficiency reduces pulmonary fibrosis in transgenic mice.

Despite evidence that implicates transforming growth factor-alpha (TGF-alpha) in the pathogenesis of acute lung injury, the contribution of TGF-alpha to the fibroproliferative response is unknown. To determine whether the development of pulmonary fibrosis depends on TGF-alpha, we induced lung injury with bleomycin in TGF-alpha null-mutation transgenic mice and wild-type mice. Lung hydroxyproline content was 1.3, 1.2, and 1.6 times greater in wild-genotype mice than in TGF-alpha-deficient animals at Days 10, 21, and 28, respectively, after a single intratracheal injection of bleomycin. At Days 7 and 10 after bleomycin treatment, lung total RNA content was 1.5 times greater in wild-genotype mice than in TGF-alpha-deficient animals. There was no significant difference between mice of the two genotypes in lung total DNA content or nuclear labeling indices after bleomycin administration. Wild-genotype mice had significantly higher lung fibrosis scores at Days 7 and 14 after bleomycin treatment than did TGF-alpha-deficient animals. There was no significant difference between TGF-alpha-deficient mice and wild-genotype mice in lung inflammation scores after bleomycin administration. To determine whether expression of other members of the epidermal growth factor (EGF) family is increased after bleomycin-induced injury, we measured lung EGF and heparin-binding- epidermal growth factor (HB-EGF) mRNA levels. Steady-state HB-EGF mRNA levels were 321% and 478% of control values in bleomycin-treated lungs at Days 7 and 10, respectively, but were not significantly different in TGF-alpha-deficient and in wild-genotype mice. EGF mRNA was not detected in normal or bleomycin-treated lungs of mice of either genotype. These results show that TGF-alpha contributes significantly to the pathogenesis of pulmonary fibrosis after bleomycin-induced injury, and that compensatory increases in other EGF family members do not occur in TGF-alpha-deficient mice.

Animals↗

PubMed1987

Correlation of changes in pulmonary surfactant phospholipids with compliance in bleomycin-induced pulmonary fibrosis in the rat.

Qualitative and quantitative analysis was performed on phospholipids isolated from bronchoalveolar lavage fluid during the development of pulmonary fibrosis in the rat. A single transtracheal injection of 2.0 units of bleomycin was administered to rats to induce lung injury. Animals were killed at 0, 3, 7, 14, 30, and 120 days after bleomycin treatment. Total lipid phosphorus in BAL from animals given bleomycin increased from 1.6 mumol/lung in normal animals to 3.2 mumol/lung at 14 and 30 days. The increase in phospholipids was primarily in phosphatidylcholine with minor increases in phosphatidylinositol and phosphatidylethanolamine. These quantitative changes were accompanied by qualitative changes that included an increase in the percentage of total phosphatidylcholine, disaturated phosphatidylcholine, and phosphatidylinositol. In contrast, the percentage of phosphatidylglycerol was significantly reduced. Plasma phospholipid analysis indicated that these alterations were not due to plasma contamination. The functional significance of the phospholipid changes was assessed by comparing air- and saline-filled compliance measurements at similar times after bleomycin. Abnormal compliance measurements were observed at 3, 7, and 14 days after bleomycin. At 3 and 7 days the predominant compliance defect was at the air-liquid interface; however, at 14 days, when phospholipids were significantly elevated, the defect was primarily due to tissue components.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗