nitrogen-dioxide and Hyperplasia

On the model of chronic obstructive pulmonary disease, the effect of therapy with low-molecular-weight peptides on restructuring and functional activity of bronchial epithelium for restoring the immune and barrier function of the lungs and prevention of inflammatory process progression was studied. Chronic obstructive pulmonary disease was modeled in rats by 60-day intermittent exposure to NO2. Administration of tetrapeptide Bronchogen for 1 month eliminates symptoms of remodeling of the bronchial epithelium and lung tissue typical of chronic obstructive pulmonary disease (goblet cell hyperplasia, squamous metaplasia, lymphocytic infiltration and emphysema, and restoration of ciliated cells). Enhanced production of secretory IgA, a local immunity marker, attested to normalization of functional activity of bronchial epithelium, while normalization of cell composition and profile of proinflammatory cytokines in the bronchoalveolar space reflected reduction of neutrophilic inflammation.

Topics: Animals; Bronchoalveolar Lavage Fluid; Cilia; Goblet Cells; Hyperplasia; Immunoglobulin A; Interleukin-8; Leukocyte Elastase; Lung; Male; Neutrophil Infiltration; Nitrogen Dioxide; Oligopeptides; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Rats; Rats, Wistar; Respiratory Mucosa; Respiratory System Agents; Tumor Necrosis Factor-alpha

We investigated the effect of intratracheal injections of an extract of suspended particulate matter (SPM) obtained from the urban ambient air of Tokyo, upon the development of proliferative lesions of pulmonary endocrine cells (PECs) in the rat. We also examined the modification effects of nitrogen dioxide, sulfur dioxide, or both of them on the PEC lesions. Male F344 rats were divided into six experimental groups of 5 animals each. Twenty animals were treated with intratracheal instillations of SPM admixed with carbon once a week for 4 weeks with or without additional gaseous exposure (6 ppm nitrogen dioxide or 4 ppm sulfur dioxide) 16 hrs a day for 11 months. Five animals were given intratracheal injections of carbon suspended in saline and the other five were untreated. The subcardiac lobes of the right lung were fixed with 4% paraformaldehyde, and embedded in paraffin. PEC hyperplasias and papillomas were counted in 200 serial sections, 4 microns thick. The average incidences of PEC hyperplasia in the untreated animals and in those treated with carbon were 194 and 200/cm3, respectively. The average incidences of PEC hyperplasia in the animals exposed to SPM tar only, SPM tar plus nitrogen dioxide and sulfur dioxide, SPM tar with nitrogen dioxide and SPM tar with sulfur dioxide were 376, 378, 372 and 349/cm3, respectively. These were significantly higher than the levels of the control animals, and additional gaseous stimuli had no effect on the incidence of PEC hyperplasia. Besides PEC hyperplasia, a few PEC papillomas were found in the animals treated with SPM tar, regardless of gaseous exposure, but in the control animals no papilloma was evident. Thus, compounds in airborne particulates are considered to be responsible for the development of PEC hyperplasias and papillomas.

Topics: Administration, Inhalation; Air Pollutants; Animals; APUD Cells; Calcitonin Gene-Related Peptide; Hyperplasia; Intubation, Intratracheal; Lung; Lung Neoplasms; Male; Nitrogen Dioxide; Papilloma; Rats; Rats, Inbred F344; Sulfur Dioxide

Chlorphentermine HCl (CP) was used to induce preexisting alveolar alterations resembling a pulmonary lipidosis in mice to study these effects on the severity and duration of nitrogen dioxide (NO2) toxicity. Results indicated that a daily dose of 120 mg/kg for 14 days produced consistent histopathologic changes characterized by an accumulation of large foamy macrophages. Male Swiss-Webster mice were divided into a control and three treatment groups. Group 1 received 120 mg/kg CP po daily for 2 weeks followed by exposure to air for 48 hr. Group 2 received 20 ppm NO2 for 48 hr via whole-body inhalation, and group 3 received 120 mg/kg CP daily for 2 weeks followed by 20 ppm NO2 for 48 hr. The fourth group served as a nontreated control and received water in place of CP and air in place of NO2. All groups were compared by morphologic evaluation of pulmonary tissues at the light and electron microscopic levels at Days 0, 1, 3, 5, and 7 after the 48-hr exposure to air or NO2. In a second experiment using the same treatment groups, thin-section light microscopy was used to count the number of type I and type II cells and macrophages. NO2 exposure alone caused deaths in 20.8 and 18.5% of the mice in the two studies, but no deaths were seen in the combination groups from both experiments. Histopathologic evaluation showed a typical cellular response to the NO2 exposure, but differences were noted between the two groups receiving NO2 on this treatment. There was increased type II cell hyperplasia and terminal bronchiolitis on Days 0 and 1 but less on Days 3 to 7 in the combination group compared to the NO2 alone group. CP treatment prior to NO2 exposure caused less terminal bronchiolar epithelial hyperplasia and less pulmonary edema than was seen in the NO2 along group. The CP treatment appeared to protect against the lethal effects of NO2 at the concentration and time of exposure used and altered the cellular repair mechanism that occurs in response to NO2 toxicity. CP treatment prior to NO2 exposure caused significantly less loss of type I cells and less increase in type II cells due to NO2 damage. The combination treatment also caused an increase in macrophages greater than that seen in either individual treatment, and this number remained increased through 5 days post-NO2 exposure, whereas the NO2 alone caused a steady increase in macrophages following the exposure until Day 3.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Animals; Body Weight; Cell Count; Chlorphentermine; Hyperplasia; Lipidoses; Lung; Macrophages; Male; Mice; Microscopy, Electron; Nitrogen Dioxide; Phentermine

Experiments were performed to study the influence of concentration, exposure pattern, and length of exposure on the degree and extent of morphological alterations in the NO2-exposed rat lung. Four weeks of continuous exposure to 20 mg NO2/m3 consecutively revealed damage and loss of cilia, replacement of desquamated type I pneumocytes by type II pneumocytes resulting in a cuboidal epithelial lining, an influx of alveolar macrophages, and hypertrophy and hyperplasia of the bronchiolar epithelium. The animals recovered almost completely from the induced lesions within 8 days. Continuous exposure to 1, 2.5, or 5 mg/m3 displayed minimal alterations in the 5 mg/m3 group. The effects increased with exposure time. Intermittent or continuous exposure to 20 mg NO2/m3 resulted in minor differences after 4 weeks. The onset of the lesions was delayed and the massive influx of alveolar macrophages in the continuously exposed animals failed to appear in the intermittently exposed animals. This work demonstrates that in subacute experiments: Concentration plays a more important role in inducing pulmonary lesions than exposure time when the product of concentration and time is kept constant. This effect is stronger during intermittent exposure than during continuous exposure. Continuous exposure seems to be a more important factor with regard to a macrophage response than intermittent exposure. The rat lung has a large capacity to repair almost completely from damage caused by short-term NO2 exposure.

Topics: Animals; Dose-Response Relationship, Drug; Hyperplasia; Lung; Macrophages; Male; Microscopy, Electron, Scanning; Nitrogen Dioxide; Pulmonary Emphysema; Rats; Rats, Inbred Strains

The amine precursor uptake and decarboxylase (APUD) cells and neuroepithelial bodies (NEBs) in airways of adult rats have been studied by immunocytochemical methods for the presence of adrenocorticotropic hormone (ACTH), growth hormone (hGH), calcitonin, and bombesin in control animals and following exposure to nitrosodiethylamine and nitrogen dioxide (NO2). Calcitonin-like immunoreactivity (CLIR) is present in APUD cells of the trachea and bronchioles and in NEBs in the lung. Rats treated with nitrosodiethylamine and NO2 exhibit increased numbers of argyrophilic cells but no increase in cells containing specific intracytoplasmic CLIR. The presence of ACTH, hGH, and bombesin in respiratory tract APUD cells was not observed. These studies indicate that APUD cells in the trachea and bronchioles of adult rats harbor endocrine cells with immunohistochemical characteristics similar to C cells of the thyroid, and that these cell do not appear to be altered in number when rats are treated with agents known to produce an increase in APUD cells.

Topics: Animals; APUD Cells; Diethylnitrosamine; Hyperplasia; Immunoenzyme Techniques; Nitrogen Dioxide; Nitrosamines; Rats; Rats, Inbred Strains; Respiratory System

A method of quantitating the airways amine precursor uptake decarboxylase (APUD) cells is proposed that relates these cells to total airway epithelial cells or airway length. In control rats, these values were 0.13 APUD cells/100 epithelial cells in the trachea, 0.03 in the large airways, and 0.02 in the small airways. In order to evaluate the ability of this method to determine changes in number of APUD cells, rats were exposed to diethylnitrosamine (DEN) and nitrogen dioxide (NO2), which have been reported to increase the number of airways APUD cells. The NO2 exposure was associated with a twofold increase in APUD cells of the trachea only without associated epithelial hyperplasia; DEN produced marked epithelial hyperplasia in the trachea and bronchi with a disproportionate increase in APUD cells in the bronchial epithelium only. The basis of this differential effect requires further study.

Topics: Animals; APUD Cells; Cell Count; Diethylnitrosamine; Epithelial Cells; Hyperplasia; Nitrogen Dioxide; Nitrosamines; Rats; Rats, Inbred Strains; Respiratory System; Trachea

Beagle dogs (104) comprising one control and seven treatment groups were exposed 16 hours daily for 68 months to filtered air, raw or photochemically reacted auto exhaust, oxides of sulfur or nitrogen, or their combinations. After a further 32 to 36 months in clean air, morphologic examination of lungs by light microscopy, scanning electron microscopy, and transmission electron microscopy revealed two important exposure-related lesions. They were enlargement of air spaces in proximal acinar regions, with and without increases in the number and size of interalveolar pores, and hyperplasia of nonciliated bronchiolar cells. Proximal enlargment of air spaces was most severe, both subjectively and morphometrically, in those dogs exposed to oxides of nitrogen, oxides of sulfur, or oxides of sulfur with photochemically reacted auto exhause. In contrast, hyperplasia of nonciliated bronchiolar cells was most severe in dogs exposed to raw auto exhaust alone or with oxides of sulfur. The air space enlargement and hyperplasia of bronchiolar epithelium correlated with functional impairment reported as occurring in these dogs. Foci of ciliary loss with and without squamous metaplasia were occasionally observed in trachea and bronchi. The observations indicate that enlargement of proximal acinar air spaces with some loss of interalveolar septa can develop in the absence of alveolar fenestrations. The persistnt nature of bronchiolar cell proliferations in such circumstances was also demonstrated. Two major toxicologic implications are (1) the production of permanent lung damage by much lower concentrations of pollutants than previously reported and (2) the apparent lack of additive or synergistic effects between oxidant gases and sulfur oxides.

Topics: Air Pollutants; Animals; Atmosphere Exposure Chambers; Bronchi; Dogs; Emphysema; Hyperplasia; Lung; Male; Metaplasia; Nitric Oxide; Nitrogen Dioxide; Organ Size; Pulmonary Alveoli; Sulfur Oxides; Total Lung Capacity; Trachea; Vehicle Emissions

At long-term exposure to 5 ppm NO2 (w/w), courses of histological changes in the epithelium of the terminal bronchioles of rats were observed. In the course of the experiment the first alterative changes were expressed by the loss of cilia and cell differentiation. The changes were followed by epithelial hyperplasia, leading to conspicuous narrowing of the lumen of bronchioles. After the phase of hyperplasia a phase of reparation followed, leading to the development of nonciliated epithelium without determinable Clara cells, with areas of uniform multi-layered epithelium. At the same time, in the longest interval of 11 weeks new alterative changes analogous to those found at the beginning of the experiment were observed.

Topics: Animals; Bronchi; Cilia; Epithelial Cells; Epithelium; Hyperplasia; Nitrogen Dioxide; Pulmonary Alveoli; Rats; Time Factors

Topics: Animals; Basement Membrane; Bronchi; Cilia; Cytoplasm; Environmental Exposure; Epithelium; Hyperplasia; Lung; Macrophages; Male; Microscopy, Electron; Nitrogen Dioxide; Pulmonary Alveoli; Rats; Time Factors

Topics: Animals; Bronchitis; Carbon; Cytoplasm; Epithelium; Hyperplasia; Indicators and Reagents; Intubation, Intratracheal; Lung; Macrophages; Male; Microscopy; Microscopy, Electron; Necrosis; Nitrates; Nitrogen Dioxide; Phagocytosis; Pneumonia; Pulmonary Alveoli; Pulmonary Fibrosis; Rats; Staining and Labeling

Topics: Animals; Guinea Pigs; Hyperplasia; Lipids; Lung; Lung Diseases; Male; Methods; Microscopy, Electron; Nitrogen Dioxide; Pulmonary Alveoli

Topics: Acids; Aldehydes; Animals; Bronchi; Carcinogens; Epithelium; Hyperplasia; Infections; Lung; Male; Metaplasia; Mice; Nasal Mucosa; Nitrogen Dioxide; Nose; Orthomyxoviridae Infections; Respiratory System; Smoking; Trachea