Biomedical subjects

P Camner

Publications and source records attributed to P Camner.

At least 37 records · Page 2Linked to original sources

PubMed1999

Clearance in small ciliated airways in allergic asthmatics after bronchial allergen provocation.

BACKGROUND: Asthma tends to affect mucociliary clearance, as assessed from measurements in large airways. However, there is no knowledge about clearance in the smallest airways of the tracheobronchial region in acute exacerbation of asthma. OBJECTIVE: The aim of the study was to investigate clearance from the bronchiolar region in patients with allergic asthma in a situation resembling a mild acute exacerbation of the disease. We also aimed to compare clearance data with corresponding data found for healthy subjects and asthmatics on therapy. METHODS: Tracheobronchial clearance was studied twice in 9 patients with mild asthma of the allergic type after inhalation of 6 microm (aerodynamic diameter) monodisperse Teflon particles labelled with 111In. At one exposure, inhalation was performed 4 h after bronchial provocation with an allergen the patients were allergic to. The second exposure was a control measurement. The particles were inhaled at an extremely slow flow, 0.05 liter/s, which gives deposition mainly in the small ciliated airways (bronchioles). Lung retention was measured at 0, 24, 48 and 72 h. RESULTS: All patients demonstrated an early asthmatic reaction of varying degree after bronchial provocation. There was significant clearance of radioaerosol in each 24-hour period for both exposures, with the possible exception of the period between 24 and 48 h for the provocation exposure, with similar fractions of retained particles at all points of time. The retained fractions were significantly larger compared to a group of healthy subjects and asthmatics on regular treatment with anti-inflammatory drugs. CONCLUSIONS: Our results indicate that in allergic asthmatics a bronchial allergen provocation with an early asthmatic reaction does not significantly influence overall clearance from the bronchiolar region. However, in the present group of patients, retention in small ciliated airways was significantly higher compared to healthy subjects and asthmatics on regular treatment.

Adult↗

PubMed1999

Production of nitric oxide by rat alveolar macrophages stimulated by Cryptococcus neoformans or Aspergillus fumigatus.

Cryptococcus neoformans and Aspergillus fumigatus are airborne fungi and the alveolar macrophages (AM) constitute a first line of host defence against both pathogens. We investigated the ability of rat AM to produce nitric oxide (NO) when challenged in vitro with C. neoformans, A. fumigatus conidia or inert silica particles alone and together with interferon gamma (IFN-Gamma). The role of NO in the killing of C. neoformans as well as the relationship between phagocytosis of the yeast or A. fumigatus conidia and NO production by AM were studied. Both fungi, but not the inert particles induced a small but significant increase in NO production by AM. A synergistically enhanced NO production by AM was observed when each fungus, but not silica particles, were incubated together with IFN-Gamma. AM treated with IFN-Gamma and challenged with C. neoformans showed higher killing activity than untreated AM, a finding that correlated with increased NO production by AM. Both effects were reduced by an inhibitor of NO synthesis. Increased NO production by IFN-Gamma activated AM was found together with an increased accumulated attachment of A. fumigatus conidia and serum opsonized, but not unopsonized C. neoformans. The IFN-Gamma dependent increase in accumulated attachment of the fungi might be responsible for the synergistic effect of the fungi and IFN-Gamma on the NO production. Our data suggest that activated rat AM might efficiently use the antimicrobial nitric oxide system in the defence against these pathogens in the normal host.

Animals↗

PubMed1998

Does airway responsiveness increase after skin sensitisation to 3-carene: a study in isolated guinea pig lungs.

Guinea pigs were sensitised by dermal exposure to 3-carene according to the modified cumulative contact enhancement test (CCET) protocol. Lungs from sensitised and non-sensitised animals were then perfused with buffer and exposed for a period of 10 min to two different air concentrations of 3-carene, 600 and 3000 mg/m3. 3-Carene caused a statistically significant bronchoconstriction even at the relatively low concentration of 600 mg/m3 and the constriction was dose dependent. 600 mg/m3 of 3-carene caused a reduction of 19% in conductance capacity and 16% in compliance capacity. 3000 mg/m3 of 3-carene decreased lung compliance and conductance by 43 and 31%, respectively. The lungs from sensitised animals tended to show a greater response than lungs obtained from control animals. The lower concentration of 3-carene is close to and may even be below, occupational limit values in Sweden, Germany and USA.

Allergens↗

PubMed1998

Differences between rat alveolar and interstitial macrophages 5 wk after quartz exposure.

Macrophages play an essential role in pulmonary host defense. We investigated differences between rat alveolar (AM) and interstitial (IM) macrophages after exposure in vivo to quartz, an inducer of intensive alveolitis. Rats were exposed to 0.5 ml of saline without (n = 8) or with (n = 8) 10 mg of quartz by intratracheal instillation. In a third group (n = 8), 10 mg of surfactant were added to the quartz mixture. Five weeks later, AM were recovered by bronchoalveolar lavage and IM by mechanical fragmentation of the lung, followed by enzymatic treatment. Contamination of AM to the IM fraction was calculated to be 12-15%. After quartz exposure, the expression of major histocompatibility complex class Ia was increased in both AM and IM fractions. The receptor corresponding to human complement receptor 3 increased in AM after quartz exposure, and AM from quartz-exposed animals had a lower metabolic activation. Our findings indicate that IM are immunocompetent cells and that differences between AM and IM fractions occur upon quartz-induced inflammation. This response is not affected by addition of surfactant.

Animals↗

PubMed1997

In vitro interaction of alveolar macrophages and Aspergillus fumigatus.

In vitro interaction of alveolar macrophages (AM) from rats with conidia from Aspergillus fumigatus and Aspergillus candidus as well as inert control particles (amorphous silica) of similar diameter (about 3 microns), was studied. Experimental observations showed that both kinds of conidia were phagocytized significantly faster by AM than were the control particles due to a faster rate of attachment, but even more so due to a faster rate of ingestion. Quantitative nitroblue tetrazolium reduction by AM reflecting their oxidative metabolism and oxygen radical release was increased in response to both kinds of conidia by a factor of 2-3 during the process of phagocytosis, as well as 24 hr after the onset of phagocytosis, compared to corresponding conditions with inert particles and to resting macrophages. The mean pH in phagolysosomes with each of the conidia tended to be higher after 3 hr but was significantly lower after 24 hr than in the phagolysosomes with the control particles. After 3 hr there was a considerable percentage (around 8%) of phagolysosomes with pH > or = 6.5 and after 24 hr there was still a small percentage (0.7%) of such phagolysosomes for each of the conidia. Such a fraction was not observed for the control particles. Electron microscopic studies showed passages between phagolysosomes and AM surface with both kinds of conidia. The occurrence of such unsealed phagolysosomes might explain the percentage of phagolysosomes with high pH. Hence, Aspergillus conidia in unsealed macrophage vacuoles mediate an increased oxygen radical release from the macrophages, a process which in the long run might cause lung damage.

Animals↗

PubMed1997

Reaction of human alveolar macrophages to exposure to Aspergillus fumigatus and inert particles.

In vitro interaction of human alveolar macrophages (AM) with heat-killed conidia from Aspergillus fumigatus and inert silica particles of similar size, about 3 microns, was studied. The conidia were phagocytized significantly faster by AM than were the control particles partly due to the faster rate of attachment but especially due to the faster rate of ingestion. Quantitative nitroblue tetrazolium (NBT) reduction by AM, reflecting their release of oxygen radicals, was increased by a factor of 2 to 3 in response to the conidia during phagocytosis. The silica particles induced a moderate but significant increase in NBT reduction. Conidia, but not silica particles, showed a considerable percentage (around 8%) of phagolysosomes with neutral pH after 3 h and a smaller percentage (around 1%) after 24 h of incubation. The pH of phagolysosomes with conidia tended to be higher after 3 h, but was significantly lower after 24 h than the pH of phagolysosomes with silica particles. Despite the markedly increased oxidative metabolism there was no increase in cytokine production [interleukins (IL) 6 and 8 and tumor necrosis factor alpha (TNF-alpha)] after exposure to conidia. The silica particles induced a significant decrease in IL-6 and IL-8 production and a tendency toward decreased production of TNF-alpha. The occurrence of phagolysosomes with neutral pH suggests unsealed phagolysosomes from which not only oxygen metabolites but also enzymes might escape from the cell. Lung damage may thus be the result of repeated or long-term exposure to Aspergillus conidia.

Adolescent↗

PubMed1997

In vivo interaction between alveolar macrophages and Cryptococcus neoformans.

In vivo interactions of rabbit alveolar macrophages (AM) and Cryptococcus neoformans, a yeast pathogenic for humans, were studied. As a control, inert silica particles of a similar diameter (5-6 microns) were used. Of 16 rabbits, 6 were instilled intratracheally with fluorescein-labelled heat-killed C. neoformans, 6 with fluorescein-labelled silica particles and 4 with saline only. After 24 h, the AM were collected by lung lavage, and phagocytosis, oxidative metabolism, phagolysosomal pH and morphology were studied. The accumulated number of yeasts attached to the AM was almost the same for C. neoformans as for the silica particles. The ingested fraction of C. neoformans was even higher than that of the silica particles. Quantitative NBT reduction by the AM, reflecting their oxidative metabolism, was markedly increased by exposure to C. neoformans for 24 h. The phagolysosomal pH was on the average lower in phagolysosomes with C. neoformans than with the silica particles, although approximately 2% of the phagolysosomes with C. neoformans had neutral pH. Phagolysosomes with neutral pH was not observed for silica particles. Electron microscopy showed presence of C. neoformans in phagolysosomes of AM. The conclusion of this study is that the phagocytic activity, oxidative metabolism and phagolysosomal pH AM against C. neoformans are significant 24 h after the exposure.

Animals↗

PubMed1997

Alveolar macrophage reaction to Candida species.

Candida species are increasingly important fungal pathogens. The reaction of rat alveolar macrophages (AM) to Candida albicans was compared with that to C. glabrata and C. krusei. Phagocytosis of C. glabrata was similar to that of C. albicans, but significantly slower for C. krusei due to reduced attachment. After opsonization, attachment of C. albicans and C. krusei to AM was significantly increased and there was no significant difference between the two species. The oxidative metabolism of AM with candida species was two to three times higher than that of the resting AM both during and 24 h after the phagocytosis. All three species showed a considerable fraction (5-10%) of phagolysosomes with pH > or = 6.5 after 3 h and a smaller percentage (1%) after 24 h.

Animals↗

PubMed1997

Functional, morphological, and phenotypical differences between rat alveolar and interstitial macrophages.

Alveolar macrophages (AM) and interstitial macrophages (IM) from rat lungs were characterized with respect to morphology, phagocytosis, adhesion properties, and phenotype. AM were recovered by lung lavage and IM by treatment of the lung tissue with DNAse and collagenase. The AM were enzyme treated in the same way as the IM. The IM were smaller than AM and had a higher nuclear to cytoplasm ratio. They had markedly lower phagocytic capacity. The attachment of particles to the cell surface was significantly lower in IM than in AM, but the capacity to ingest the particles was the same. Adherence to vitronectin- as well as fibronectin-coated surfaces was significantly higher in AM. The phagolysosomal pH was similar in IM and AM, around pH 5, indicating that dissolution of inorganic particles can take place effectively also in IM. Five surface receptors were studied, and the expression differed significantly in all five between AM and IM. The expression of OX-1 (CD 45), a common leukocyte antigen, was significantly higher on AM as was the expression of CD 71 (transferrin receptor). The receptor density for OX-42 was higher on a fraction of IM. This might be compatible with a stronger interaction between these cells and, for example, matrix components. IM had more surface antigen expressing MHC class Ia (OX-6) and CD 54. Both receptors are important for the antigen presentation capacity of macrophages. These findings show profound differences in phenotype between AM and IM and indicate that IM is a highly immunocompetent cell and should not be regarded only as a precursor to AM.

Animals↗

PubMed1996

Anticryptococcal activity by alveolar macrophages from rats treated with cortisone acetate during different periods of time.

The effect of cortisone acetate (CA) treatment on the anticryptococcal activity by rat alveolar macrophages (AM) was investigated. The animals received a weekly dose of 5 mg CA during 1, 2, 3 or 4 weeks. Following the final dose the AM were collected by lung lavage and challenged with Cryptococcus neoformans. Parallel experiments with silica particles of a similar size were performed. The phagocytic function was assessed using a fluorescence method that distinguishes between attached and ingested particles. The oxidative metabolism was studied by the nitroblue tetrazolium (NBT) reduction test. The accumulated attachment (a measure of the attachment process) of cryptococci and silica particles per AM was significantly depressed after the third and fourth week of CA treatment. The ingested fraction (a measure of the ingestion process) of cryptococci but not of silica particles showed a small but significant decrease after the fourth week. The NBT reduction of the unstimulated AM and those stimulated with either the cryptococci or silica particles for 24 h was significantly reduced after the fourth week of treatment. In conclusion, these results demonstrate that high dose CA treatment primarily affects the attachment of the cryptococci to the AM and to a lesser extent also the ingestion process. In addition, it decreases the NBT reduction by AM in response to the yeast. The impairment of the AM anticryptococcal activity by high doses of CA constitutes a risk of dissemination of C. neoformans from the lungs.

Animals↗

PubMed1996

Tracheobronchial deposition and clearance in small airways in asthmatic subjects.

Asthma tends to impair mucociliary clearance, as assessed from measurements in large airways. However, very little is known about clearance in the smallest airways of the tracheobronchial region. Deposition and clearance was estimated in 11 subjects with stable asymptomatic asthma and 10 healthy subjects after inhalation of 6 microns (aerodynamic diameter) monodisperse Teflon particles labelled with 111In. The particles were inhaled at an extremely slow flow, 0.05 L.s-1. Theoretical calculations and experimental data in healthy subjects using this slow flow support an enhanced deposition in the tracheobronchial region, in particular in the small ciliated airways (bronchioles). Lung retention was measured at 0, 24, 48 and 72 h. Clearance was significant every 24 h both for asthmatic and healthy subjects, with similar fractions of retained particles at all time-points. The fractions of tracheobronchially-deposited particles were on average 41 and 47% for asthmatic and healthy subjects, respectively, as compared to a maximal deposition of 30% using a normal inhalation flow (0.5 L.s-1). No significant correlation was found between lung retention and lung function, either in asthmatics or in healthy subjects. Our results indicate that particles clear equally well from small ciliated airways in asthmatic and healthy subjects, maybe as a consequence of an optimal asthma therapy. Furthermore, our results show that it is possible to enhance tracheobronchial deposition both in healthy and asthmatic subjects, i.e. practically independent of airway dimensions, by inhaling rather large aerosol particles extremely slowly. This may be a useful therapeutic approach.

Administration, Inhalation↗

PubMed1996

Oropharyngeal deposition of 3.5 microns particles inhaled through an elongated mouthpiece.

We previously studied the deposition of inhaled particles in the oropharynx of asthmatic patients, and found that a pharyngeal narrowing during inhalation seems to be one reason for high oropharyngeal deposition. In the present study, we investigated whether by-passing a larger part of the oral cavity by using an elongated mouthpiece would reduce deposition in the oropharynx, and increase deposition in the lungs. Deposition in the oropharynx and in the lungs was estimated in nine patients with obstructive airway diseases. In earlier investigations, three of these patients had repeatedly shown extremely high oropharyngeal deposition (> 70%). In the present study, the patients inhaled 3.5 microns (aerodynamic diameter) radiolabelled Teflon particles at 0.5 L.s-1, with and without an individually adapted elongated mouthpiece. Radioactivity was measured using a profile scanner. On average, oropharyngeal deposition was 27% (range 12-45%) and 30% (range 11-77%) of the total amount of particles deposited in the body, with and without elongated mouthpiece, respectively. There was no significant difference between these values (p > 0.05), nor between the values of lung deposition. However, oropharyngeal deposition was markedly reduced, with a corresponding increase in lung deposition, by the elongated mouthpiece in the one and only patient who still showed extremely high oropharyngeal deposition (> 70%). Our study shows that lengthening of the mouthpiece is not sufficient to reduce average deposition of aerosol particles in the oropharynx in patients with comparatively normal deposition values. This result, however, does not exclude a beneficial effect in patients with extremely high oropharyngeal deposition.

Administration, Inhalation↗

PubMed1995

Added external resistance reduces oropharyngeal deposition and increases lung deposition of aerosol particles in asthmatics.

Mouth and throat, and regional lung deposition was estimated in fifteen asthmatic subjects for 3.6-microns (aerodynamic diameter) radiolabeled polytetrafluoroethylene (Teflon) particles inhaled at 0.5 L/s with and without added external resistance. Radioactivity was measured by a profile scanner. Behavior of the pharynx and larynx was assessed by fiberoptic laryngoscopy. Mean mouth and throat deposition was 22% (range, 13 to 47%) and 33% (range, 12 to 84%) with and without resistance (p < 0.05), respectively. A marked reduction in mouth and throat deposition (range, 20 to 44%), with a corresponding increase in lung deposition, was observed especially in the six subjects with mouth and throat deposition values > 30% at inhalation without resistance. Furthermore, a small (mean 8%) but significant (p < 0.05) increase in peripheral lung deposition, estimated as retention at 24 h, was found at inhalation with increased resistance. The fiberoptic examination showed wide intersubject variability in the pharynx and larynx, with tendencies toward higher mouth and throat deposition with pharyngeal narrowing, and significantly (p < 0.05) lower lung retention with laryngeal narrowing. Our results show that an external resistance reduces mouth and throat deposition and increases deposition and retention of aerosol particles in the lungs in asthmatic individuals.

Adult↗

PubMed1995

Repeatability of airway deposition and tracheobronchial clearance rate over three days in chronic bronchitis.

Previous investigations on tracheobronchial clearance in chronic bronchitis or chronic obstructive pulmonary disease (COPD) have usually referred to measurements during a short time-period, i.e. a few hours. The purpose of this study, therefore, was to study regional particle deposition and tracheobronchial clearance during 72 h. In 14 patients with chronic bronchitis clearance of 111In-labelled 3.6 micrograms Teflon particles and lung function were measured on two occasions, with an interval of 2 weeks. Lung retention of test particles was measured at 0, 24, 48 and 72 h using a profile scanner. The weight of expectorated sputum samples was measured after the two clearance measurements. The particle retentions at all time-points were reproducible, as seen from the two measurements ( r > 0.90). The fast clearance phase was completed within 72 h. No correlation between sputum volume and clearance was seen. There was a significant negative correlation between airway resistance and the 72 h retention (r= -0.66), and an even better correlation between specific airway resistance and the 72 h retention (r = -0.82), indicating more central deposition in obstructed airways. There was no significant correlation between lung function tests reflecting smaller airways and the 72 h retentions. Deposition data agreed well with theoretical calculations and experimental data in healthy subjects. In spite of earlier findings that mucociliary transport is usually severely impaired in chronic bronchitis and COPD, the present results indicate that overall tracheobronchial mucus clearance in these patients is fairly effective, probably due to a productive cough. Alveolar deposition may be estimated by measurements of the 72 h retention in subjects with chronic obstructive pulmonary disease. The 72 h retention is dependent mainly on the calibre of larger airways. The present method of studying airway clearance during 3 days is highly reproducible.

Adult↗

PubMed1994

Effects of spermidine on function and ultrastructure of alveolar macrophages.

It is known that spermidine and other naturally occurring polyamines accumulate in rat lung slices by an energy-dependent uptake process and that alveolar macrophages (AM) have a greater rate of uptake than has the total lung cell population. In the present study rat AMs were incubated with spermidine, which resulted in a marked and significant (P < 0.002) decrease in phagocytosis of heat-killed yeast cells at concentrations 0.2 and 0.5 mM and a tendency to decrease at 0.05 mM. The number of microtubules surrounding the centrioles was measured using electron microscopy and appeared to be decreased at concentrations 0.2 and 0.5 mM. There was no affect on phagolysosomal pH. The results suggest that spermidine might affect the defense against inhaled pollutants and microbes, especially when spermidine levels are increased, as they are under conditions with high mitotic activity, e.g., in tumors.

Animals↗

PubMed1994

Phagolysosomal pH in alveolar macrophages from smokers and non-smokers.

1. Alveolar macrophages efficiently phagocytize particles deposited in the alveolar part of the lung. Phagolysosomal pH in alveolar macrophages from rabbits, dogs, baboons and guinea pigs is around 5 pH units. A low pH is of importance for clearance of inorganic particles and probably also for defence against bacteria and fungi. 2. Phagolysosomal pH in alveolar macrophages from smokers and non-smokers was measured using fluorescein-conjugated amorphous silica particles as a probe. pH was the same in both groups and similar to earlier studies on alveolar macrophages from animals. 3. The morphological picture between alveolar macrophages from smokers and non-smokers differed clearly with a high number of dense inclusions of great variation in size and shape in macrophages from smokers. Ingested test particles were located in all types of inclusions. 4. We conclude that phagolysosomal pH in human alveolar macrophages is similar to that in several animal species and that it is rather insensitive to influence from the environment.

Adult↗

PubMed1994

Deposition of inhaled particles in the mouth and throat of asthmatic subjects.

We previously studied the deposition of inhaled particles in the mouth and throat of asthmatic patients, and found large, reproducible differences among subjects. In the present study, we examined whether anatomical and/or functional differences in the pharynx and larynx could underlie this interindividual variation. Deposition in the mouth and throat, and in the lung was estimated in 16 asthmatic subjects after inhalation of 3.6 microns (aerodynamic diameter) monodisperse Teflon particles labelled with 111In. The particles were inhaled at a flow rate of 0.5 l.s-1 with maximally deep breaths. Radioactivity was measured by external scanning over head and neck, lungs and stomach, immediately after the inhalation. Radioactivity in the lungs was also measured 24 h later. A measure of the total amount of particles deposited in the mouth and throat was obtained from the added activities in mouthwash, head and neck, and stomach, immediately after the inhalation of the test particles. Pharynx and larynx function was examined by fibreoptic laryngoscopy performed during a corresponding inhalation procedure. Deposition in the mouth and throat varied widely among the subjects, ranging 9-76% (median 12%). We found two subpopulations, 13 subjects in the range 9-34%, and 3 subjects with > 70% deposition. Deviations in pharyngeal configuration during inhalation were significantly related to high mouth and throat deposition, whereas functional differences in the larynx were not. Our study shows that mouth and throat deposition may be extremely high in some asthmatics, and that pharyngeal configuration affects deposition of particles in the mouth and throat.

Adult↗

PubMed1993

Inhalation of cobalt by sensitised guinea pigs: effects on the lungs.

Two groups, each of six guinea pigs, were sensitised by the application of cobalt chloride (CoCl2) on the skin on day 0, 2, 7, and 9 and the establishment of contact allergy was confirmed by patch testing on day 21. A further six animals were not sensitised. Starting on day 42 one sensitised group and the non-sensitised group were exposed by inhalation to 2.4 (0.8) mg (mean (SD)) Co in the form of CoCl2 for six hours a day for two weeks. After exposure the lungs were lavaged and the cells obtained were studied by light and electron microscopy. In the sensitised exposed group much more lavage liquid was retained in the lungs than in the other two groups; although more liquid was instilled in the lungs of this group, on average only 5 (range 2.5-10) ml were recovered compared with 10 ml in all animals in the other two groups. In the sensitised exposed group, the percentage of neutrophils and eosinophils tended to be higher than in the non-sensitised exposed group. The results indicate that the lungs of guinea pigs allergic to contact with Co react differently to inhaled Co compared with those of non-sensitised ones.

Administration, Inhalation↗