Biomedical subjects

R B Schlesinger

Publications and source records attributed to R B Schlesinger.

At least 55 records · Page 3Linked to original sources

PubMed1988

Alveolar macrophage-stimulated neutrophil and monocyte migration: effects of in vitro ozone exposure.

The ability of rabbit alveolar macrophages (AM) to release factors which stimulate the migration of peripheral blood neutrophils and monocytes was examined, and the influence of in vitro ozone exposure on this secretory activity was investigated. To evaluate the ability of AM to release leukocyte chemotactic activity, AM obtained by bronchoalveolar lavage were established in monolayer or suspension culture, with and without added zymosan, for 2 and 6 hr. The resulting macrophage-conditioned medium was tested for chemotactic activity using modified Boyden-type chambers and rabbit peripheral blood neutrophils or monocytes as the responding cells. The results demonstrate that substrate attachment (monolayer culture) and/or zymosan phagocytosis can stimulate AM to release chemoattractants for monocytes and neutrophils. Additionally, the results suggest that AM are constitutively producing low levels of monocyte chemotactic factors. The effects of in vitro ozone exposure on the secretion of chemotactic activity was investigated by exposing monolayer cultures of AM to air, 0.1, 0.3, or 1.2 ppm ozone for 2 hr. Macrophage-conditioned medium was harvested immediately, 2 and 6 hr postexposure, and tested for chemotactic activity. Exposure to 0.3 and 1.2 ppm ozone significantly increased the AM secretion of factors which stimulated neutrophil migration; additionally, the results strongly suggest that ozone can augment the ability of AM to stimulate monocyte migration. These results imply a role for the AM in the recruitment of inflammatory cells after ozone inhalation.

Animals↗

PubMed1988

Response of the tracheobronchial mucociliary clearance system to repeated irritant exposure: effect of sulfuric acid mist on function and structure.

This study was designed to determine quantitative and temporal alterations in tracheobronchial mucociliary clearance function and structure due to repeated inhalation exposures to a common irritant, sulfuric acid mist. Rabbits were exposed to 250 micrograms/m3 sulfuric acid (0.3 micron) for 1 h/day, 5 days/week, for up to 1 year, with some animals allowed a 3-month recovery period following the end of the acid exposures. Control animals received temperature- and humidity-conditioned water vapor. At intervals of 2 to 4 weeks, animals inhaled a radioactively tagged tracer aerosol (ferric oxide microspheres, 4.5 micron), and its clearance via mucociliary transport from the thorax was monitored by external serial counting. Clearance became slower during the first month of acid exposure, and this slowing became progressive with time through the end of the 12-month exposure period. After cessation of acid exposure, clearance became extremely slow and did not return to normal by the end of the follow-up period. To assess specific histological changes in the tracheobronchial tree, groups of rabbits were killed after 4, 8, or 12 months of exposure and after the follow-up period. Tissue samples from each lung were embedded in plastic, sectioned at 3 micron, and stained with hematoxylin and eosin or alcian blue/periodic acid-Schiff (AB/PAS). Acid exposure changed the airway diameter distribution compared to the control; except for the follow-up group, all acid-exposed animals had a shift to smaller airways. Acid inhalation also caused an increase in epithelial secretory cell density and a shift from PAS to AB staining of glycoprotein within secretory cells, both of which were unresolved by 3 months after the exposures ceased. No evidence of inflammation was found in any of the animals. Thus, repeated exposures to H2SO4 resulted in a slowing of mucociliary clearance that was associated with alterations in airway morphometry and morphology. Such changes may be involved in the early pathogenesis of chronic airway disease.

Aerosols↗

PubMed1987

Functional assessment of rabbit alveolar macrophages following intermittent inhalation exposures to sulfuric acid mist.

Sulfuric acid (H2SO4) aerosols are common in both ambient and occupational environments. This study examined the numbers and selected in vitro functional properties of alveolar macrophages recovered from rabbits undergoing inhalation exposure to 0.5 mg/m3 submicrometer (0.3 micron) H2SO4 for 2 hr/day. Bronchoalveolar lavage was performed on Days 3, 7, and 14 during the exposure period (specifically, 24 hr after either 2, 6, or 13 exposures). Total cell numbers and macrophage counts were increased on Day 3, but returned to control levels by Day 7; no change in polymorphonuclear leukocytes was observed at any time point. Macrophage substrate attachment was not affected by exposures to H2SO4, but random mobility was severely depressed at Days 7 and 14. The numbers of phagocytically active macrophages and the level of such activity were increased on Day 3, but became depressed by Day 14. These results demonstrate significant alterations in important functional properties of alveolar macrophages due to short-term intermittent exposures to H2SO4 aerosols; these changes have implications for the ability of the lungs to maintain adequate defense against deposited viable and nonviable particles.

Administration, Inhalation↗

PubMed1987

Intermittent exposures to mixed atmospheres of nitrogen dioxide and sulfuric acid: effect on particle clearance from the respiratory region of rabbit lungs.

Nitrogen dioxide (NO2) and sulfuric acid (H2SO4) are important constituents of the gas-particle complex in ambient air. The purpose of this study was to examine the effects of combined exposures upon the clearance of insoluble tracer particles from the respiratory region of the lungs. Rabbits were the animal model, and were exposed for 2 h/day for 14 days to either 0.3 ppm NO2, 1 ppm NO2, or 500 microgram/m3 H2SO4 alone, or to mixtures of the low and high NO2 concentrations with acid. Inhaled singly, both concentrations of NO2 accelerated clearance while H2SO4 retarded it, compared to control. Exposure to the combination of 0.3 ppm NO2 plus H2SO4 resulted in a response which was not different from that due to the acid alone. However, exposure to 1 ppm NO2 plus H2SO4 resulted in a clearance pattern which differed from that of both NO2 and H2SO4, but was more similar to that of the latter.

Aerosols↗

PubMed1987

Effect of repeated exposures to nitrogen dioxide and sulfuric acid mist alone or in combination on mucociliary clearance from the lungs of rabbits.

The biological response to ambient air pollution may be a function of specific combinations of pollutants. Groups of rabbits were exposed to NO2 (0.3 ppm or 1 ppm) with and without H2SO4 (0.5 mg/m3) for 2 hr/day for up to 14 days for assessment of effects upon mucociliary clearance of tracer particles from the tracheobronchial tree. Exposure to NO2 did not alter clearance, while exposure to H2SO4 produced a retardation toward the middle of the exposure series. The combination of 0.3 ppm NO2 with H2SO4 resulted in a speeding of clearance, while no change from control was seen with the mixture employing 1 ppm NO2 with acid. These results emphasize the importance of performing studies with pollutant mixtures, since it is not always possible to extrapolate responses from studies examining effects of individual pollutants.

Administration, Intranasal↗

PubMed1987

Mucociliary clearance from the lungs of rabbits following single and intermittent exposures to ozone.

This study examined the effects of ozone (O3) inhalation on mucociliary clearance from the tracheobronchial tree. Rabbits were exposed for 2 h at 0.1, 0.25, and 0.6 ppm or for 2 h/d for 14 consecutive days at 0.25 and 0.6 ppm. Clearance was assessed by measuring the retention of radioactivity tagged, inert tracer particles inhaled immediately after the single 2-h exposure, or 24 h after 2, 7, or 14 of the daily exposures. Single exposures resulted in a concentration-related trend toward retarded particle clearance, with a statistically significant difference occurring after exposure to 0.6 ppm. Intermittent exposures produced no significant change in clearance rate, although there was a suggestion of retarded clearance at early time points at both 0.25 and 0.6 ppm.

Animals↗

PubMed1987

Acute and subchronic ozone inhalation in the rabbit: response of alveolar macrophages.

Ozone is a potent oxidant gas and a common constituent of photochemical smog. This investigation evaluated the numbers and functional capabilities of alveolar macrophages (AM) recovered from rabbits undergoing acute and subchronic ozone exposure. Bronchoalveolar lavage was performed immediately, 24 h, and 7 d after acute (2-h) exposure to 0.1 or 1.2 ppm ozone, and on d 3, 7, and 14 during subchronic (2 h/d X 13 d) exposure to 0.1 ppm ozone. After acute exposure to 1.2 ppm, a marked increase in lavaged neutrophils was observed at 24 h. A single exposure to 0.1 ppm resulted in increased AM at 7 d, while repeated exposures resulted in an increase in AM and neutrophils on d 7 and 14. AM phagocytosis was depressed immediately and 24 h after acute exposure to 0.1 ppm, and at all time points after exposure to 1.2 ppm. Repeated exposures to 0.1 ppm produced reductions in the numbers of phagocytically active AM on d 3 and 7, with a return to control levels by d 14. Substrate attachment by AM was impaired immediately after exposure to 1.2 ppm; AM mobility was not altered by any of the ozone exposures. The results of these studies demonstrated significant alterations in the numbers and functional properties of AM as a result of single or repeated exposure to 0.1 ppm ozone, a level below the current National Ambient Air Quality Standard. These findings indicate that levels of ozone frequently encountered in areas of high photochemical air pollution can elicit a pulmonary inflammatory response and can impair pulmonary defense capabilities.

Administration, Inhalation↗

PubMed1987

Intermittent inhalation of nitrogen dioxide: effects on rabbit alveolar macrophages.

Rabbits were exposed to 0.3 or 1 ppm NO2 for 2 h/d and the effects on alveolar macrophages recovered by bronchopulmonary lavage at 3 time points during the exposure series were assessed. Cells were examined 24 h after 2, 6, or 13 exposures, i.e., on d 3, 7, and 14. There was no change in the viability or numbers of macrophages recovered at any time, nor was an inflammatory response produced. The ability of macrophages to attach to a surface was not affected by exposure. Random mobility was reduced at d 3 in the 0.3 ppm exposure series, but was not different from control after any of the 1 ppm exposures. The phagocytic index, i.e., the fraction of viable cells able to phagocytize latex particles, was not affected by NO2 exposure. However, phagocytic capacity--i.e., the numbers of phagocytizing cells that internalized specific numbers of particles--was different from control on d 3 with both levels of NO2. At 0.3 ppm, particle uptake was reduced, while at 1 ppm it was enhanced in that a greater fraction of cells contained a large number of latex particles. The results show that phagocytic capacity and random mobility are sensitive indices of response to NO2 and that adaptation to the exposures apparently occurred in that both phagocytosis and mobility returned to control levels by d 7 and remained there through the duration of the exposure series.

Administration, Inhalation↗

PubMed1987

Effects of intermittent inhalation exposures to mixed atmospheres of NO2 and H2SO4 on rabbit alveolar macrophages.

Rabbits were exposed (2h/d) to atmospheres consisting of 0.5 mg/m3 (0.3 micron) H2SO4 plus NO2 at either 0.3 (low) or 1 ppm (high). Animals were sacrificed 24 h after 2, 6, or 13 exposures, and cells were recovered from the lungs by bronchopulmonary lavage. Exposure to high NO2 with acid resulted in an increase in neutrophils at all time points and an increase in phagocytic capacity of macrophages after two or six exposures. On the other hand, exposure to the low NO2 with acid resulted in depressed phagocytic capacity and mobility. The results were compared with those for NO2 or H2SO4 given alone.

Animals↗

PubMed1986

Sulfuric acid-induced airway hyperresponsiveness.

Rabbits were exposed to submicrometer sulfuric acid (H2SO4) mist at 250 micrograms/m3 for 1 hr/day, 5 days/week for 4, 8, or 12 months in order to examine the effects on bronchial responsiveness, which was assessed at the end of each exposure series by administration (iv) of doubling doses of acetylcholine and measurement of pulmonary resistance (RL). Dynamic compliance (Cdyn) and respiratory rate (f) were also measured following agonist challenge. Animals exposed for 4 months showed increased sensitivity to acetylcholine (dose required to produce a 150% increase in RL), and there was an increase in reactivity (slope of dose vs change in RL) by 8 months, with a leveling off of the response after this time. No changes in Cdyn or f were noted at any time. Thus, repeated exposures to H2SO4 resulted in the production of hyperresponsive airways in previously healthy animals. This has implications for the role of nonspecific irritants in the pathogenesis of airway disease.

Acetylcholine↗

PubMed1986

Measurement of particle clearance from the alveolar region of the rabbit respiratory tract.

This paper describes a method for the measurement of the clearance of inert, insoluble radioactively tagged tracer particles from the alveolar region of the rabbit respiratory tract. The technique uses a fixed detector for noninvasive, external monitoring. Validation of the method is presented, as is the clearance pattern of 3.5-micron latex particles as measured for 56 days postexposure. The clearance of latex deposited within the alveolar region can be described by two phases within this time frame, having half-times of 4.9 and 30.1 days, respectively. Clearance of latex initially deposited on the tracheobronchial tree was essentially complete by 2 days after exposure.

Animals↗

PubMed1986

Early alveolar clearance of particles in rabbits undergoing acute and subchronic exposure to ozone.

The concentration-response relationship for changes in early alveolar clearance resulting from O3 inhalation were investigated. Groups of five rabbits were exposed to 0.0, 0.1, 0.6, or 1.2 ppm O3, 2 hr/day X 1 day; or to 0.0, 0.1, or 0.6 ppm O3, 2 hr/day X 13 days. Following the initial O3 exposure all rabbits inhaled an aerosol of 85Sr-tagged, 3.0-micron, polystyrene latex particles and particle retention was determined daily for the following 14 days. Single exposures to O3 produced a concentration related trend from accelerated clearance at 0.1 ppm to a transient impairment of clearance at 1.2 ppm. Subchronic exposure resulted in a significant acceleration of particle clearance at both 0.1 and 0.6 ppm, with the effect more pronounced at the higher level. These results demonstrate that single or repeated exposure of rabbits to 0.1 ppm O3, a level below the current National Ambient Air Quality Standard, produces alterations in early alveolar clearance. The effects observed at higher levels of O3 appeared to depend on both the concentration and exposure regime; acute exposures produced a concentration related trend toward an initial retardation of clearance, which was followed by an acceleration in particle removal, while repeated exposures resulted in a persistent acceleration of clearance.

Animals↗

PubMed1986

Early alveolar clearance in rabbits intermittently exposed to sulfuric acid mist.

During the course of 1-h/d, 5-d/wk exposure to submicrometer sulfuric acid mist at 250 micrograms/m3, rabbits were exposed to a radioactively tagged polystyrene latex tracer aerosol to assess clearance from the alveolar region during the period 2-14 d after tracer exposure. The latex was administered on d 1, 57, and 240 following the start of the H2SO4 exposures. Early alveolar clearance was found to be accelerated during the first test, and this acceleration was maintained throughout the 8-mo monitoring period.

Aerosols↗

PubMed1986

Changes in early alveolar particle clearance due to single and repeated nitrogen dioxide exposures in the rabbit.

To better understand the potential health risks associated with short-term NO2 exposures, a study was conducted to examine the effects of single and repeated NO2 exposures on the clearance of inert tracer particles from the alveolar region of rabbit lungs. Single 2-h exposures to 0.3, 1.0, 3.0, and 10.0 ppm produced a concentration-related acceleration in alveolar particle clearance, which resulted in greater particle removal when compared to control. The greatest response was produced at the lower NO2 levels, where as much as 40% more particles were cleared when compared to control. Fewer particles were cleared following a 10.0-ppm NO2 exposure when compared to the lower NO2 levels, and there were indications from the clearance pattern that the higher level was beginning to slow clearance, although an actual retardation was not found. Repeated 14-d exposures (2 h/d) to 1.0 or 10.0 ppm NO2 produced a response similar to a single exposure at the same concentration, suggesting a certain degree of adaptation was produced after the initial exposures. Possible mechanisms for these differences in clearance patterns are discussed. The results of this study demonstrated altered alveolar clearance following short-term NO2 exposure at environmentally relevant concentrations; changes in this important host defense mechanism may be indicative of some underlying pathologic condition.

Animals↗

PubMed1986

Assessment of early alveolar particle clearance and macrophage function following an acute inhalation of sulfuric acid mist.

Rabbits were exposed to submicrometer sulfuric acid mist at 1 mg/m3 for 1 hr to assess effects on alveolar region clearance of a polystyrene latex tracer aerosol. Bronchopulmonary lavage was performed at selected times after exposure for functional characterization of alveolar macrophages. In vivo, clearance was accelerated in acid exposed animals relative to sham controls. Acid exposure produced no change in the viability or numbers of macrophages recovered. Although an increase in the number of polymorphonuclear leukocytes, primary neutrophils, was observed by 1 hr in both acid and sham groups, compared to nonexposed controls, levels were normal by 12 hr in shams but continued elevated in the acid group through 24 hr. Reduced in vitro macrophage adherence was observed after acid exposure. In vivo uptake of the tracer particles by macrophages was enhanced during the first 3 hr after acid exposure and in vitro phagocytosis by polymorphonuclear leukocytes was increased through 48 hr post-exposure. The results indicate some functional alterations in free cells after in vivo exposure to H2SO4 and the production of a mild inflammatory response. This latter was associated with an acceleration of inert particle clearance from the alveolar region.

Aerosols↗

PubMed1985

Morphometric variability of the human upper bronchial tree.

Available morphometric models of the human tracheobronchial tree are based on measurements of a small number of individuals from a few laboratories. In order to determine the degree of intersubject variability, and its relationship to intrasubject variability, analysis of airway lengths, diameters and branching angles was performed using solid casts of the upper bronchial trees from a series of human lungs. The results indicate that there are significant differences between subjects. Inter- and intrasubject variabilities should be considered in occupational and environmental hazard evaluation, and when extrapolating and modeling inhalation toxicologic data.

Adolescent↗

PubMed1985

Clearance from the respiratory tract.

Alterations in the clearance of insoluble particles have been shown to provide a sensitive indicator of response due to exposure to various inhaled materials. This paper reviews clearance mechanisms, the significance of clearance changes, and the methodology used to assess them.

Aerosols↗

PubMed1985

Comparative deposition of inhaled aerosols in experimental animals and humans: a review.

The biological effects of inhaled aerosols are often related to their site(s) of deposition within the respiratory tract. However, deposition patterns may differ between humans and those experimental animals commonly used in inhalation toxicology studies, making cross-species risk extrapolations difficult. This paper reviews the factors that control deposition and synthesizes much of the available data on comparative regional deposition.

Aerosols↗