PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “PULMONARY FIBROSIS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,243 records · Page 69Linked to original sources
PubMed2005

Relationship of BAL and lung tissue CD4+ and CD8+ T lymphocytes, and their ratio in idiopathic pulmonary fibrosis.

BACKGROUND: Surgical biopsy specimens have shown that T lymphocytes (TLs) infiltrate lung parenchyma in patients with idiopathic pulmonary fibrosis (IPF) and might play a pathogenetic role. BAL, a far less invasive technique, has also been used for the investigation of IPF pathogenesis. However, controversy exists whether the BAL fluid cellular profile reflects the cellular composition of the lung parenchyma. STUDY OBJECTIVE: To compare infiltrating TLs subpopulations (CD4+, CD8+, and CD4+/CD8+ ratio) in lung tissue and BAL fluid. PATIENTS AND METHODS: Immunohistochemistry was performed according to the streptavidin-biotin method on the surgical biopsy specimens of 12 untreated patients with IPF. The number of CD3+, CD4+, and CD8+ TLs was determined by observer-interactive computerized image analysis (SAMBA microscopic image processor; Meylan, France). In BAL fluid, the same TLs subpopulations were evaluated by flow cytometry. RESULTS: In lung tissue, CD3+ TLs accounted for a mean (+/- SEM) of 28.8 +/- 7% of total cells, CD4+ TLs accounted for 14.5 +/- 4% of total cells (50.1 +/- 4% of CD3+ TLs), and CD8+ TLs accounted for 13.8 +/- 4% of total cells (47.4 +/- 4% of CD3+ TLs). In BAL fluid, lymphocytes accounted for 9.8 +/- 2.5% of total cells, CD4+ TLs accounted for 51.8 +/- 4% of CD3+ TLs, and CD8+ TLs accounted for 42.2 +/- 4% of CD3+ TLs. Tissue CD4+ and CD8+ TLs (expressed as a percentage of CD3+ TLs) correlated significantly with the number of CD4+ and CD8+ TLs in BAL fluid (r = 0.846 and p = 0.001 vs r = 0.692 and p = 0.013, respectively). A significant positive correlation was also found between the mean CD4+/CD8+ ratio found in tissue and BAL fluid (1.05 +/- 0.21 and 1.5 +/- 0.27, respectively; r = 0.832; p = 0.01). CONCLUSION: The results suggest that in patients with IPF, the TL subpopulations in BAL fluid reflect the pattern of lymphocytic infiltration in pulmonary parenchyma.

Bronchoalveolar Lavage Fluid↗
PubMed1986

Cellular analysis in bronchoalveolar lavage fluids in infiltrative and fibrotic stages of idiopathic pulmonary fibrosis.

We performed cellular analysis of bronchoalveolar lavage fluids (BALF) from 20 patients in different stages of idiopathic pulmonary fibrosis (IPF) and compared the results with those from 16 controls and 10 sarcoidosis patients. Patients with IPF were divided into infiltrative and fibrotic groups as diagnosed by transbronchial lung biopsy and chest x-rays. Total cell numbers counted from BALF in IPF patients were not different from those from controls and were lower than in sarcoidosis patients (p less than 0.01). Lymphocytes in BALF were significantly higher in the infiltrative type IPF than in the fibrotic type (p less than 0.05), but there was no significant difference in fibrotic type IPF and control subjects. Numbers of neutrophils and eosinophils counts were not significantly different between infiltrative type and fibrotic type. The neutrophil count in fibrotic type IPF was higher than in control subjects (p less than 0.01) but not in infiltrative type IPF. 67Ga scintiscanning uptake correlated with the lymphocyte population (r = 0.65, p less than 0.01) but with neutrophils. These findings suggest that lymphocytes play a major role in the pathogenesis of the infiltrative type of IPF and that neutrophils are related to the development of fibrotic changes in IPF.

Adrenal Cortex Hormones↗
PubMed1998

[Ischemic heart disease as a factor for hindering diagnosis of idiopathic pulmonary fibrosis].

UNLABELLED: The aim of the study was to find factors that may influence diagnostic process of idiopathic pulmonary fibrosis (IPF). Clinical presentation, lung function data and radiological changes were assessed in 57 patients with diagnosis of IPF. There were 25 females and 32 males in the study group; mean age was 61.4 +/- 10.9 years. Mean duration of symptoms in the whole group was 18.4 +/- 16.0 months. The most common symptoms were dyspnea on exertion (96.5% of cases) and cough (84.2% of cases). 56 out of 57 patients (98.2% of cases) had crackles on ausculation of the lungs. In one third of the patients clubbing of the fingers was found. Mean FVC% of predicted was 77.2 +/- 19.8%, and mean DLCO% of predicted was 61.6 +/- 16.8%. The most common associated disease was ischemic heart disease, found in 43.9% of patients. Duration of symptoms in patients with ischemic heart disease was 25.7 +/- 18.8 months and was as twice long as in the rest of the patients, 12.8 +/- 10.5 months (p < 0.005). CONCLUSIONS: 1: Associated ischemic heart disease may cause delay in establishing the diagnosis of IPF; 2. Crackles on ausculation are characteristic for IPF and together with disseminated changes on chest radiograms indicate correct diagnosis in patients with associated ischemic heart disease.

Aged↗
PubMed2004

[Experimental study on treatment of pulmonary fibrosis by Chinese drugs and integrative Chinese and Western medicine].

OBJECTIVE: To compare the effects of treatment of pulmonary fibrosis (PF) by the Chinese herbal medicines, Radix Salviae miltiorrhizae (C1), Radix Astragalus membranaceus (C2) and Caulis Tripterygium wilfordii (C3); western drugs, hydrocortisone (W1) and azathioprine (W2), and combined W2 with C3. METHODS: Eighty SD rats were divided into 8 groups. Except the 10 rats in the normal control group, the other 70 rats were made into animal model of PF by bleomycin administration, and treated with various medicines, except the 10 rats in the model control group. The treatment started from the 15th day of modeling, the model animals were perfused with C1, C2, C3, W1, W2 and W2 + C3 respectively for 14 days. Rats were sacrificed by the end of experiment, their lung tissue was taken for pathological section to conduct the pathological examination under light microscope and computerized image quantitative analysis to evaluate the effects of the treatments objectively. RESULTS: The therapeutic effect of C1 was the best, that of W1 the second and C2 the third. W2 showed some effect, but PF worsened after the combined therapy of W2 and C3 was applied. CONCLUSION: Radix Salviae miltiorrhizae shows definite therapeutic effect in treating PF.

Animals↗
PubMed1993

[Pathogenesis of idiopathic interstitial pneumonia/idiopathic pulmonary fibrosis: cellular and molecular biology of the disease].

Idiopathic interstitial pneumonia (IIP), which is referred to as "idiopathic pulmonary fibrosis (IPF)" in US and European countries or "cryptogenic fibrosing alveolitis (CFA)" in UK, is considered to result from an uncontrolled, chronic inflammatory process in the lower respiratory tract and alveoli of the lung. It is conceivable that some hereditary background may contribute to the disease in susceptible individuals. In IPF, alveolitis involving activation of alveolar macrophages (AM), neutrophils, T- and B-lymphocytes and/or other inflammatory cell types precedes the injury to the lung parenchyma and interstitial fibrosis. Activation and accumulation of cellular components in the disease seem to be modulated by a variety of biological substances such as cytokines, chemotactic factors and adhesion molecules. Exposure to inorganic dusts or viral infection also may trigger activation of AM. The injury to the alveolar epithelium, capillary endothelial cells and extracellular matrix mediated by oxidants and/or proteases produced by AM and neutrophils results in the derangement of the lung parenchyma. Subsequent fibrotic change of the lung interstitium is characterized by the accumulation of mesenchymal cells such as fibroblasts and deposition of their connective tissue produces within the alveolar walls. In this process, AM is considered to play a major role by secreting growth factors for mesenchymal cells, although alveolar epithelial and endothelial cells also seem to participate in activating mesenchymal cell proliferation in IPF. Possibly, connective tissue synthesis and/or degradation may be altered in the process of IPF, although there is no direct evidence for this so far. Thus, IPF is a chronic inflammatory disease in which inflammatory processes of the alveoli injure the lung parenchyma and modulate the proliferation of mesenchymal cells which result in the fibrotic change. The pathogenesis of the disease involves multiple cellular components of the lower respiratory tract through modulation of gene expression and protein synthesis of a variety of biological factors.

Gene Expression Regulation↗
PubMed1999

[Idiopathic pulmonary fibrosis of the upper lobe: a case report].

A 26-year-old man was admitted to our hospital complaining of exertional dyspnea. Chest x-ray films disclosed reticulonodular shadows predominantly in the upper fields of both lungs, but no apical cap. Lung biopsy specimens obtained from the upper lobe by video-assisted thoracoscopy revealed subpleural elasto-fibrosis. Also, specimens obtained from the lower lobes disclosed micro-honeycombing due to peri-lobular fibrosis resembling usual interstitial pneumonia. Although pneumothorax occurred repeatedly, the lungs reinflated on each occasion without artificial intervention. Similar radiographic findings had been obtained on the patient's father, who died of idiopathic pulmonary fibrosis at the age of 56. Idiopathic pulmonary upper lobe fibrosis was conclusively diagnosed because the patient exhibited most of the features originally described by Amitani et al.

Adult↗
PubMed2003

Reduced expression of cyclooxygenase (COX) in idiopathic pulmonary fibrosis and sarcoidosis.

AIMS: To test the hypothesis that cyclooxygenase (COX)-1 or COX-2 expression is defective in lungs in idiopathic pulmonary fibrosis (IPF) and to characterize the cellular distribution. IPF is a progressive inflammatory lung disorder with an adverse prognosis. Previous work has shown that prostaglandin E2 (PGE2) regulates collagen deposition and fibroblast proliferation and a defect in COX regulation may contribute to the fibrosis that occurs in IPF. METHODS: Immunohistochemistry was utilized to determine COX immunoreactivity in lung sections from 25 IPF, six sarcoidosis and 14 control subjects. RESULTS: COX-1 and COX-2 expression in bronchiolar epithelial cells was significantly lower in IPF and sarcoidosis than in controls. No significant difference was found in COX-2 expression between macrophages in IPF and control sections, but COX-2 was reduced in macrophages in sarcoidosis compared with controls. CONCLUSIONS: These studies confirm COX-2 loss in bronchial epithelial cells but not macrophages in IPF, and show for the first time reduced constitutive COX-1 expression in epithelial cells and macrophages. Similar abnormalities were observed in sarcoidosis.

Adult↗
PubMed2005

CD8+ T lymphocytes in lung tissue from patients with idiopathic pulmonary fibrosis.

BACKGROUND: Several studies have implicated a role of inflammation in the pathogenesis of lung damage in idiopathic pulmonary fibrosis (IPF). Parenchymal lung damage leads to defects in mechanics and gas exchange and clinically manifests with exertional dyspnea. Investigations of inflammatory cells in IPF have shown that eosinophils, neutrophils and CD8+ TLs may be associated with worse prognosis. We wished to investigate by quantitative immunohistochemistry infiltrating macrophages, neutrophils and T lymphocytes (TLs) subpopulations (CD3+, CD4+ and CD8+) in lung tissue of patients with IPF and their correlation with lung function indices and grade of dyspnoea. METHODS: Surgical biopsies of 12 patients with IPF were immunohistochemically stained with mouse monoclonal antibodies (anti-CD68 for macrophages, anti-elastase for neutrophils, and anti-CD3, anti-CD4, anti-CD8 for CD3+TLs, CD4+TLs, and CD8+TLs respectively). The number of positively stained cells was determined by observer-interactive computerized image analysis (SAMBA microscopic image processor). Cell numbers were expressed in percentage of immunopositive nuclear surface in relation to the total nuclear surface of infiltrative cells within the tissue (labeling Index). Correlations were performed between cell numbers and physiological indices [FEV1, FVC, TLC, DLCO, PaO2, PaCO2 and P(A-a)O2)] as well as dyspnoea scores assessed by the Medical Research Council (MRC) scale. RESULTS: Elastase positive cells accounted for the 7.04% +/- 1.1 of total cells, CD68+ cells for the 16.6% +/- 2, CD3+ TLs for the 28.8% +/- 7, CD4+ TLs for the 14.5 +/- 4 and CD8+ TLs for the 13.8 +/- 4. CD8+TLs correlated inversely with FVC % predicted (rs = -0.67, p = 0.01), TLC % predicted (rs = -0.68, p = 0.01), DLCO % predicted (rs = -0.61, p = 0.04), and PaO2 (rs = -0.60, p = 0.04). Positive correlations were found between CD8+TLs and P(A-a)O2 (rs = 0.65, p = 0.02) and CD8+TLs and MRC score (rs = 0.63, p = 0.02). Additionally, CD68+ cells presented negative correlations with both FVC % predicted (rs = -0.80, p = 0.002) and FEV1 % predicted (rs = -0.68, p = 0.01). CONCLUSION: In UIP/IPF tissue infiltrating mononuclear cells and especially CD8+ TLs are associated with the grade of dyspnoea and functional parameters of disease severity implicating that they might play a role in its pathogenesis.

CD8-Positive T-Lymphocytes↗
PubMed2006

Different angiogenic activity in pulmonary sarcoidosis and idiopathic pulmonary fibrosis.

BACKGROUND: Recent evidence has shown that several chemokines--including those involved in angiogenesis--have been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and sarcoidosis. We speculated that these differences could be attributed to distinct angiogenic and angiostatic profiles. This hypothesis was investigated by estimating the levels of three angiogenic chemokines (growth-related gene [GRO]-alpha, epithelial neutrophil-activating protein [ENA]-78, and interleukin [IL]-8), and three angiostatic chemokines (monokine induced by interferon (IFN)-gamma [MIG], IFN-gamma-inducible protein [IP]-10, and IFN-gamma-inducible T-cell alpha chemoattractant) in serum and BAL fluid (BALF). METHODS: We studied prospectively 20 patients with sarcoidosis (median age, 46 years; range, 25 to 65 years), 20 patients with IPF (median age, 68 years; range, 40 to 75 years), and 10 normal subjects (median age, 39 years; range, 26 to 60 years). RESULTS: The GRO-a serum and BALF levels of IPF patients were found significantly increased in comparison with healthy subjects (799 pg/mL vs 294 pg/mL [p = 0.022] and 1,827 pg/mL vs 94 pg/mL [p < 0.001], respectively) and sarcoidosis patients (799 pg/mL vs 44 pg/mL [p < 0.001] and 1,827 pg/mL vs 214 pg/mL [p < 0.001], respectively). Moreover, ENA-78 and IL-8 BALF levels in IPF patients were significantly higher compared with sarcoidosis patients (191 pg/mL vs 30 pg/mL [p < 0.001] and 640 pg/mL vs 94 pg/mL [p = 0.03], respectively). MIG serum levels in IPF patients were found significantly upregulated in comparison with sarcoidosis patients and healthy control subjects. However, MIG and IP-10 BALF levels (1,136 pg/mL vs 66 pg/mL [p < 0.001] and 112 pg/mL vs 56 pg/mL [p = 0.037], respectively) were significantly higher in sarcoidosis patients compared with IPF patients. CONCLUSIONS: Our data suggest distinct angiogenic profiles between IPF and sarcoidosis, indicating a potential different role of CXC chemokines in the local immunologic response in IPF and pulmonary sarcoidosis.

Adult↗
PubMed1984

Chemotherapy-induced fatal pulmonary fibrosis.

The case of a girl with relapsing ependymoma is described, who received BCNU and vincristine treatment. She developed progressive, pulmonary fibrosis as a consequence of chemotherapy, which lead to her death. Predisposing factors, clinical and histological findings are discussed and suggestions are made for the regular and preventive checking of the patients' pulmonary function.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Effects of pulmonary fibrosis on the distribution of edema. Morphometric analysis.

We tested the hypothesis that in advanced pulmonary fibrosis, edema is redistributed away from the relatively noncompliant interstitium and predominantly floods alveoli. Severe left lung fibrosis was produced in six dogs with radiation and intratracheal bleomycin and, 24 mo later, hydrostatic edema was induced by infusing 20% body weight Ringer's lactate. Previously we had found, by computed tomography scanning and gravimetry, that similar amounts of water per unit volume accumulated in control and fibrotic lungs; semiquantitative light microscopic grading showed less interstitial and more alveolar edema in the fibrotic lungs. In the present study, we extended these observations with detailed morphometric assessment of volume fractions and absolute volumes of the pulmonary compartments, and we examined the lungs with electron microscopy. We found a twofold rise in the volume fractions of connective tissue and alveolar edema (p < 0.05) and a 50% reduction of air and of interstitial edema in fibrotic lobes (p < 0.05). There was a marked reduction in the absolute volume of edema, paralleling the reduction in lung volume in fibrosis, and minimal gravity-dependent edema gradients in both control and fibrotic lungs. In the latter, evidenced by electron microscopy, the interstitial edema was randomly distributed, whereas in the control lungs, it was found primarily around extra-alveolar vessels and airways, not in the alveolo-capillary septa. We conclude that fibrosis profoundly affects the distribution of edema in the lung.

Animals↗
PubMed2002

[The effect of dipyridamole and adenosine on pulmonary fibrosis in mice].

OBJECTIVE: To evaluate the effect of dipyridamole (DPM) and adenosine (ADO) on interstitial pulmonary fibrosis in mice. METHODS: 100 mice injected with Bleomycin (BLM, 8.5 mg/kg) by intratracheal were divided into a control group and groups treated by DPM, ADO, DPM and theophyline (TH). Pulmonary pathology from day 4 to day 30 observations was studied by light and electron microscope. RESULTS: Alveolar epithelial cell necrosis, lung tissue lesions by hypoxia and interstitial fibrosis were found in the BLM group after day 10. The necrotic epithelial cell, fibroblast proliferation, and the hypoxia induced tissue damage were less prominent, and the number and phagocytic function of macrophages were increased in the DPM and ADO treated groups. In the TH treated group, necrotic epithelial cells increased, the lung tissue was ischemic, and the differentiation of monocytes in pulmonary interstitial was slower. CONCLUSION: DPM and ADO can inhibit fibroblast proliferation by improving microcirculation and promoting macrophage development and alveolar space reconstruction.

Adenosine↗
PubMed2006

Exhaled markers of oxidative stress in idiopathic pulmonary fibrosis.

BACKGROUND: Expired breath condensate (EBC) has never been used to explore the level of oxidative stress in idiopathic pulmonary fibrosis (IPF). Therefore, the aim of this study was to measure the levels of H2O2 and 8-isoprostane, as biomarkers of oxidative stress, in the EBC of patients with IPF. MATERIALS AND METHODS: We investigated 16 patients with IPF and 15 healthy subjects as the control group. The levels of H2O2 and 8-isoprostane were measured in the EBC of all subjects and were compared between the IPF and control groups. In patients with IPF, H2O2 and 8-isoprostane were further correlated with pulmonary function tests (PFTs), the resting pO2 and the differential cell count from the bronchoalveolar lavage fluid (BALF). RESULTS: The mean (95%CI) concentration of H2O2 was increased in the patients with IPF compared with the normal subjects (0.36, 0.24-0.47 microM vs. 0.16, 0.10-0.23 microM, P=0.003). The mean (95%CI) concentration of 8-isoprostane was also increased in the patients with IPF compared with the controls (74, 38-110 pg mL-1 vs. 33, 28-39 pg mL-1, P=0.02). In the patients with IPF, the diffusing capacity of the lung for carbon monoxide was negatively correlated with the levels of H2O2 in EBC (P=0.03, r=-0.58). No other correlation was found between the oxidative stress markers in the EBC and PFT values, pO2 or BALF cell count. CONCLUSIONS: Our data suggest that H2O2 and 8-isoprostane are increased in the EBC of patients with IPF. H2O2 may be correlated with the severity of the disease in IPF.

Adult↗
PubMed1994

High-resolution CT and pulmonary function tests in collagen vascular disease: comparison with idiopathic pulmonary fibrosis.

To estimate whether the lung abnormalities seen in collagen vascular diseases (CVD) were similar or distinct to those seen in idiopathic pulmonary fibrosis (IPF), and to ascertain whether the extent of the abnormalities on high-resolution CT (HRCT) correlated with pulmonary function, we reviewed HRCT findings and pulmonary function test results of 64 patients with either CVD (n = 55) or IPF (n = 9). Response to corticosteroid treatment was also evaluated in 20 of the 64. High incidence of honeycomb lesion was observed in IPF (9/9, 100%) and in progressive systemic sclerosis (PSS) (11/14, 79%). CVD, except for PSS, had a low incidence of honeycomb lesion (27%). On the other hand, incidence of ground-glass shadow in CVD (47/55, 85%) was the same as that in IPF (8/9, 89%). Diffusing capacity significantly correlated with the extent of all parenchymal abnormalities in all CVD and IPF, with honeycomb lesion in PSS, and with ground-glass shadow or air-space consolidation in CVD except for PSS (r < -0.7, P < 0.001). In all 15 cases in which corticosteroid therapy was effective, no honeycomb lesions were seen. Collagen vascular disease, except for PSS, had a different pattern of disease than IPF. The morphologic changes seen on HRCT correlated well with pulmonary function in CVD.

Collagen Diseases↗
PubMed1984

Drug-induced pulmonary fibrosis.

The lung is a primary target of cell injury in patients receiving cytotoxic drugs, and in many cases the reaction is severe enough to produce diffuse pulmonary fibrosis. Although many different agents may damage the lung, the patterns of cellular injury and repair are relatively constant. Using bleomycin toxicity as an example, it has been shown that, after IV injection, the selective site of lung injury is the vascular endothelium; this is followed by the accumulation of interstitial edema and later by necrosis of Type I epithelial cells. In normal repair, rapid proliferation of Type II cells, followed by differentiation to Type I, restores the epithelial surface without fibrosis. However, after bleomycin, Type II cell proliferation is frequently followed by abnormal differentiation to a metaplastic form of epithelium. Fibroblast proliferation accompanies this abnormal epithelial response which is related either to selective retention of bleomycin by epithelial cells or to the toxic effects of administering more drug at the time of Type II cell division. It is concluded that diffuse interstitial fibrosis results from prolonged disturbance of the normal epithelial-mesenchymal interrelationships at the alveolar wall. Disruption of the fibroblastic control system by extensive epithelial necrosis or by delayed or inappropriate repair may be the key factor in instigating fibroblast proliferation and subsequent deposition of collagen. This mechanism may account for the development of diffuse fibrosis or fibrosing alveolitis in response to a variety of pulmonary toxins.

Animals↗
PubMed2002

Outcome of patients with idiopathic pulmonary fibrosis admitted to the intensive care unit.

This retrospective study describes the clinical course of 38 patients with idiopathic pulmonary fibrosis (IPF) admitted to the intensive care unit (ICU). There were 25 males and 13 females who were the mean age of 68.3 +/- 11.5 years. Twenty patients were on corticosteroids at the time of admission to the hospital, and 24 had been on home oxygen therapy. The most common reason for ICU admission was respiratory failure. The Acute Physiology and Chronic Health Evaluation III-predicted ICU and hospital mortality rates were 12% and 26%, whereas the actual ICU and hospital mortality rates were 45% and 61%, respectively. We did not find significant differences in pulmonary function or echocardiogram findings between survivors and nonsurvivors. Mechanical ventilation was used in 19 patients (50%). Sepsis developed in nine patients. Multiple organ failure developed in 14% of the survivors and in 43% of the nonsurvivors (p = 0.14). Ninety-two percent of the hospital survivors died at a median of 2 months after discharge. These findings suggest that patients with IPF admitted to the ICU have poor short- and long-term prognosis. Patients with IPF and their families should be informed about the overall outlook when they make decisions about life support and ICU care.

Adrenal Cortex Hormones↗
PubMed1998

Kinetic alterations of angiotensin-II and nitric oxide in radiation pulmonary fibrosis.

We studied the kinetic alterations of angiotensin-II (A-II) and nitric oxide (NO) in radiation pulmonary fibrosis (RPF) to determine the roles of these two types of vasoactive substances in the pathogenesis of RPF. We irradiated the right hemithorax of male Wistar rats with single doses of 0, 15, and 30 Gy of 60Co gamma rays and we examined the lung parenchyma at 1, 3, 5, and 7 months following the radiation. The rats were killed at the stated intervals and samples were obtained from the right lung. We measured types I and III procollagen mRNA by in situ hybridization and demonstrated the synthesis and distribution of A-II in the pulmonary tissue by immunohistochemistry. The formation and kinetic alterations of types I and III collagen were analyzed under polarized light microscope using Sirius Red stain. The hydroxyproline (Hyp) content was measured in the pulmonary tissue after digestion with HCl. A-II radiation immunoactivity (RIA) was assayed in pulmonary tissue homogenate. Pulmonary NO content, NO synthase (NOS), and the angiotensin converting enzyme (ACE) activities were also measured. Our results showed that types I and III collagen genes began to be expressed 1 month after irradiation. Type I collagen gene increased significantly, reaching its peak 3 months after irradiation. As the irradiation dosage was increased from 15 to 30 Gy, the type I collagen gene content increased significantly, while type III significantly decreased. The Hyp content increased with the passage of time after irradiation. Pulmonary A-II RIA increased significantly with the dose of irradiation and was chiefly produced by fibroblasts and macrophages in the interstitium, bronchiolar epithelium, and the anteriolar wall. Pulmonary NO and NOS activities decreased following irradiation. One month following irradiation, the expression of the type I collagen gene begins to increase, with a significant increase in both Hyp and type I collagen 3 months after irradiation. The histogenesis of RPF may be related to A-II. The interstitial cells, the bronchiolar epithelium, and the arteriolar wall can produce A-II and need not pass through the ACE pathway. Our results suggest that the A-II increase and NO decrease may have a role in the pathogenesis of RPF.

Angiotensin II↗