Six rabbits were exposed for 4 months (5 days/week, 6 h/day) and 6 rabbits for 8 months to approx. 0.1 mg/m3 of metallic nickel dust (U.S. threshold limit value (TLV) 1 mg/m3). Another 8 rabbits were exposed for 4-6 weeks (5 days/week, 6 h/day) to 0.3 mg/m3 (as Ni) of nickel chloride (U.S. TLV 0.1 mg/m3). After exposure lungs were lavaged. Concentration of lysozyme in the lavage fluid was estimated with the lyso-plate technique (agar plates with heat-killed Micrococcus lysodeikticus) after macrophages had been removed. All 3 exposed groups had markedly lower concentrations of lysozyme than corresponding controls. Mean values in controls and exposed rabbits were: for 4 months metallic nickel dust exposure 2.3 and less than or equal to 0.04 microgram/ml; for 8 months metallic nickel dust exposure 1.4 and less than or equal to 0.5 microgram/ml; and for nickel chloride exposure 1.9 and less than or equal to 0.4 microgram/ml.

Animals↗

PubMedDate not supplied

In vitro effect of lung surfactant on alveolar macrophage defence mechanisms against Cryptococcus neoformans.

The effects of a modified natural porcine surfactant (Curosurf) on phagocytosis and killing of Cryptococcus neoformans by alveolar macrophages and on the production of superoxide anions were investigated in vitro. Attachment and ingestion were evaluated separately by a fluorescent quenching technique. The nitroblue tetrazolium reduction test was used as an indirect measurement of superoxide anion production. Killing was assessed by a colony-forming assay. Surfactant induced increased ingestion of C. neoformans, unopsonized as well as opsonized with fresh serum or anticryptococcal polyclonal IgG. Surfactant had, however, no effect on the attachment or killing of unopsonized or opsonized C. neoformans by the alveolar macrophages. In addition, the enhancement of the oxidative metabolism of the macrophages after stimulation with opsonized yeast was impaired, although the killing was not affected. This study indicates that in vitro Curosurf can influence the alveolar macrophage defence against C. neoformans by enhancing its ingestion and by interacting with the superoxide anions release from alveolar macrophages stimulated with fresh serum or anticryptococcal polyclonal IgG opsonized yeast cells.

Animals↗

PubMedDate not supplied

Increased mucociliary transport by adrenergic stimulation.

Tracheobronchial clearance of inhaled 6mum Teflon particles (density 2 gm/cu cm) tagged with technetium 99m was studied in healthy subjects by external measurement of the radioactivity in the lungs for two hours. Clearance, salivary secretion, blood pressure, and heart rate were determined in eight subjects after double-blind, subcutaneous administration of 0.25 mg terbutaline sulfate, a beta-adrenoceptor stimulating compound and vehicle, respectively, in a crossover study. Terbutaline produced a marked increase in clearance and a slight increase in heart rate, but had no important effect on salivary secretion or blood pressure. The result indicates that the blood concentrations of catecholamines might be of importance for the regulation of the mucociliary transport rate.

Adrenergic beta-Agonists↗

PubMedDate not supplied

Lung clearance of 4-micron particles coated with silver, carbon, or beryllium.

Lung clearance in rabbits during the first week after inhalation of 4-micron teflon particles tagged with chromium-51 and coated with silver, carbon, or beryllium was studied by external measurements of the radioactivity in the lungs. Ten rabbits were exposed to silver- and carbon-coated particles on two separate occasions within 3 weeks. Clearances of the two types of particles were quite similar. Clearance in eight other rabbits that had inhaled silver-coated particles was quite similar to clearance in eight rabbits that had inhaled beryllium-coated particles. The result is regarded as evidence that alveolar macrophages do not play an active role in removing intact particles from the lung the first week after inhalation.

Animals↗

PubMedDate not supplied

Human alveolar deposition of 4 micron teflon particles.

On two occasions ten healthy men inhaled with maximally deep inhalations at 0.5 1/sec a test aerosol of 4 micron teflon particles tagged with 111In. Radioactivity in the lungs was measured a few min, 24 hr, and 2, 3, and 4 days after inhalation. Retention decreased greatly between the measurements performed a few min and 24 hr after inhalation, but was similar in measurements 1 to 4 days after inhalation. Among individuals, retention varied considerably 1 to 4 days after inhalation (by a factor of 2), but the retention in each individual subject was uniform. Measuring the retention of a radioactively tagged test aerosol 1 day after inhalation, and regarding this retention as alveolar deposition, might be of value in preventive measures against certain toxic dusts.

Adult↗

PubMedDate not supplied

Alveolar macrophage response to yeasts and inert particles.

Interactions between alveolar macrophages (AM) from rats and a yeast with relatively high pathogenicity (Candida albicans), a yeast with low pathogenicity (Saccharomyces cerevisiae) and an inert control particle (amorphous silica) of similar diameters, 3-4 microns, were studied. Both yeasts were phagocytized significantly faster by AM than were the control particles and C. albicans significantly faster than S. cerevisiae. Quantitative nitroblue tetrazolium reduction by AM reflecting their oxidative metabolism was markedly increased in response to both fungi during the period of phagocytosis as well as 24 h after the phagocytosis. Macrophages with silica particles also showed a moderate but significant increase in oxidative metabolism 24 h after phagocytosis. Phagolysosomal pH was significantly higher for S. cerevisiae than the control particles after 3 and 24 h. pH in phagolysosomes with C. albicans tended to be higher after 3 h but was significantly lower after 24 h than in the phagolysosomes with silica particles. Both yeasts showed a considerable number (around 10%) of phagolysosomes with high pH > or = 6.5 after 3 h and a smaller percentage after 24 h. No such fraction could be seen for the control particles. Electron microscopy showed narrow passages from AM cell surface to phagolysosomes with particles. These passages might be more frequent in AM containing the yeasts and could explain the phagolysosomes with high pH.

Animals↗

PubMedDate not supplied

Human tracheobronchial deposition and effect of two cholinergic aerosols.

The effects of two methacholine aerosols with mass median diameters congruent to 7 and 3 microns were measured in 10 healthy subjects. The concentrations of the two aerosols were increased until forced expiratory volume in 1 s (FEV1) decreased with about 20%. Pulmonary fraction (FEV1, FVC, FEV25-75%, FEF75-85%, R(aw), and phase III of single breath O2 test) and deposition of 3.6-microns radiolabeled Teflon particles were studied before and after bronchial challenge with the two aerosols. Output from the nebulizers and size distribution were measured and from these data and from data on deposition of Teflon particles from this and seven earlier studies the doses of the two methacholine aerosols to the tracheobronchial region were calculated. The changes in all pulmonary function parameters and deposition of 3.6-microns particles were similar for the two aerosols. The calculated dose for the aerosol with the large particles was 3-4 times higher than that with the smaller particles. The results indicate greater effect of a certain dose to the tracheobronchial part of the lung if the mass is spread on many small particles than on fewer large ones.

Adult↗

PubMedDate not supplied

Phagolysosomal morphology and dissolution of cobalt oxide particles by human and rabbit alveolar macrophages.

The effect of phagolysosomal size on dissolution of cobalt oxide particles was evaluated in two different macrophage systems: alveolar macrophages (AM) of human smokers with phagolysosomes enlarged by ingested cigarette smoke products, and rabbit AM incubated in vitro with sucrose, which causes swelling of the phagolysosomes by osmosis. Human AM from smokers and nonsmokers were studied in vitro. There was no significant difference in particle dissolution between AM obtained from smokers and nonsmokers, although there was a clear difference in the morphological appearance of AM, including significantly larger phagolysosomes in smokers. Rabbit AM were incubated for 24 or 72 h with or without 80 mM sucrose in the medium. The sucrose-treated cells had 3-4 times larger phagolysosomes than untreated cells, with no major change in phagolysosomal pH. The increased size of the phagolysosomes did not affect the ability of the AM to dissolve cobalt oxide particles. Furthermore, rabbit AM showed the same ability as human AM to dissolve the cobalt oxide particles, in spite of the fact that they had markedly smaller phagolysosomes. Another difference between human and rabbit AM was that phagolysosomes in human AMs increased in size with time in culture, while rabbit AM phagolysosomes decreased in size.

Adult↗

PubMedDate not supplied

Human deposition and clearance of 6-micron particles inhaled with an extremely low flow rate.

In human experimental data, tracheobronchial deposition reaches its maximum for particles of about 6 microns inhaled at 0.5 L/s. The purpose of the present study was to investigate if tracheobronchial deposition of 6-microns particles could be increased, especially in the smaller bronchi, using an extremely slow inhalation rate. Six healthy nonsmokers inhaled monodisperse 6-microns (aerodynamic diameter) Teflon particles labeled with 111In at 0.04 L/s. Radioactivity in mouth and throat, lung, and stomach was measured immediately after inhalation by profile scanning and in the lung also after 24, 48, 72, and 96 h. There was a substantial clearance between 24 and 72 h; around 20% of the total clearance occurred between 24 and 72 h. This is in contrast to earlier studies in which only around 1% of 6-microns particles inhaled at 0.5 L/s cleared between 24 and 72 h. This indicates a markedly higher deposition in the smaller bronchi at 0.04 L/s than at 0.5 L/s. The total tracheobronchial deposition was 50%, compared to about 30% when particles were inhaled at 0.5 L/s. These findings could be therapeutic use. They also implicate the possibility of developing a diagnostic model that can separate between bronchial reactivity in large and small bronchi.

Adult↗

PubMedDate not supplied

Retention of particles inhaled in boli with and without induced bronchoconstriction.

Large lung retentions (up to 50%) of particles < or = 4 microns inhaled with a bolus technique at a penetration depth less than dead space have been reported to occur after 24 h. This retention may be due to retarded clearance of particles deposited in the airways of the tracheobronchial tract; an alternative explanation could be that particles are deposited in the alveolar region. The purpose of the present study was to confirm the occurrence of retained fractions and to study the influence of a cholinergic drug, which is assumed to give a more central particle deposition, on these retentions in human lungs after shallow aerosol bolus inhalation. Twelve healthy subjects inhaled, with a bolus technique, monodisperse Teflon particles (2.4 microns geometric diameter, 3.5 microns aerodynamic diameter), labeled with 111In. The volumetric lung depth of the inspired bolus was around 60 mL and flow rate was about 300 mL/s. Six subjects inhaled the test particles after a provocation with a cholinergic aerosol, which induced a threefold increase in airway resistance. The other six subjects inhaled a cholinergic aerosol after inhalation of the test particles or inhaled no cholinergic aerosol at all. Radioactivity in the body was measured after 0.5, 24, 48, and 72 h with a whole-body scanner with three 127 x 101-mm Nal detectors. The investigation confirmed results obtained earlier by a group in Frankfurt claiming that great retentions occur after 24 h. The retentions tended to be lower in the group receiving a bronchoconstricting drug before the bolus inhalations. There was a significant lung clearance of particles between 24 and 72 h, in contrast to the findings in earlier studies in healthy subjects and asthmatics who inhaled Teflon particles in large volumes. On the other hand, the clearance agreed well with the clearance in healthy subjects with extensive deposition of Teflon particles in the small ciliated airways, obtained by means of an extremely low inhalation flow rate. The results suggest that a considerable fraction of the particles in the bolus inhalation have been deposited in small ciliated airways in which the mucociliary transport is less efficient or in the alveolar region.

Administration, Inhalation↗