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Biomedical subjects

M Lundborg

Publications and source records attributed to M Lundborg.

At least 19 recordsLinked to original sources
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

Effects of low concentrations of 3-carene on alveolar macrophages in vitro.

Rat alveolar macrophages (AM) were incubated with the monoterpene 3-carene in vitro at the concentrations 0, 0.005, 0.05, 0.5 and 5.0 microM in culture medium for 75 min. A dose-dependent relationship was found between the cell viability and the 3-carene concentration. At 5.0 microM 3-carene, 98% of the AM were dead. The phagocytosis of heat-killed yeast particles was significantly decreased and the attachment of particles to the cell surface significantly increased at 0.5 microM 3-carene. Electron microscopy showed that about 50% of the AM lacked or had very few surface protrusions after incubation in 0.5 microM 3-carene. Thus, 3-carene seemed to affect mainly the engulfment of particles. Surfactant, 0.5 mg/ml as Curosurf, added to the incubation medium, did not affect the AM reaction to 3-carene exposure.

Animals↗
PubMed1997

Rapid diagnosis of respiratory Chlamydia pneumoniae infection by nested touchdown polymerase chain reaction compared with culture and antigen detection by EIA.

Chlamydia pneumoniae is a common cause of respiratory tract infection and community-acquired pneumonia. During an extensive outbreak of C. pneumoniae in northern Sweden, 319 respiratory samples from 129 persons were collected. Sputum, throat, and nasopharyngeal samples were obtained and analyzed by nested touchdown polymerase chain reaction (PCR), EIA, and culture in Hep-2 and McCoy cells. Serology was performed by complement fixation and microimmunofluorescence tests. By PCR, 30 patients were diagnosed with C. pneumoniae compared with 26 positive by EIA and 23 by culture. The finding of C. pneumoniae in the respiratory samples was accompanied by serology indicating acute infection in 26 (96%) of 27 patients for whom adequate sera were available. Nested PCR was sensitive and reliable for diagnosing acute respiratory C. pneumoniae infection. Sputum samples had the highest diagnostic efficacy, and the nested type of PCR was superior to one-step PCR. EIA and culture were less sensitive than nested PCR.

Acute Disease↗
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↗
PubMed1995

DNA damage in lung cells in vivo and in vitro by 1,3-butadiene and nitrogen dioxide and their photochemical reaction products.

A UV-irradiated mixture of 1,3-butadiene and nitrogen dioxide (NO2) was tested for its potency to induce DNA damage measured as single-strand breaks (SSB) in lungs of mice. Both gases were also tested separately. After 16 h exposure a UV-irradiated mixture of 40 ppm butadiene + 20 ppm NO2, but not 20 ppm butadiene + 10 ppm NO2 + UV, induced a significant increase in SSB as measured by the alkaline unwinding technique. There was no increase in the level of SSB using the alkaline elution technique during the same testing conditions. However, after 5 h exposure to 60 ppm butadiene + 30 ppm NO2 + UV both methods demonstrated a significant increase in SSB. Mice were also exposed to butadiene at 80 and 200 ppm for 16 h and at 500 ppm for 5 h. DNA damage was demonstrated in both liver and lung after 5 and 16 h (only at 200 ppm) of exposure using the unwinding technique. Using the alkaline elution assay, a significant increase in the level of SSB in lung and liver was found only after 5 h of exposure. When mice were exposed to 30 ppm NO2 for 16 h or 50 ppm for 5 h, a significant increase in SSB was found with the unwinding technique. Alveolar macrophages from mice were also exposed in vitro to the gas mixture and to butadiene and NO2 separately. In these experiments, the DNA damage was studied with the unwinding technique. A significant effect was demonstrated with 40 ppm butadiene + 20 ppm NO2 + UV. NO2 itself contributed to some extent to the increase. Reasons for the discrepancies between the unwinding and the alkaline elution techniques are discussed.

Air Pollutants↗
PubMed1995

Pulmonary macrophage function in systemic gadolinium chloride-pretreated rats.

The potential use of systemic gadolinium chloride pretreatment of rats as a tool to inhibit pulmonary macrophage function was studied by measurement of its effect on phagocytosis and nitroblue tetrazolium reduction by alveolar and interstitial macrophages. Gadolinium chloride solution was administered through the tail vein 48 h before the animals were killed. At 10 mg/kg, a dose which is generally used to inhibit Kupffer cell function, no effect on pulmonary macrophages was observed. Neither did a higher dose, 20 mg/kg, affect pulmonary macrophage function. It is concluded that gadolinium chloride pretreatment does not affect alveolar and interstitial macrophages upon systemic administration at doses and time after administration that generally depress Kupffer cell functioning.

Animals↗
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

Role of EDRF in the regulation of regional blood flow and vascular resistance at rest and during exercise in conscious dogs.

The contribution of endothelium-derived relaxing factor (EDRF) to the regulation of regional vascular resistance and tissue blood flow at rest and during acute moderate exercise was studied in chronically instrumented conscious dogs. Radioactive microspheres were injected before and during exercise to measure regional blood flow. An infusion of nitro-L-arginine (L-NA), an analogue of L-arginine, was used to inhibit the synthesis of EDRF and resulted in a significant increase in mean arterial pressure, associated with significantly elevated vascular resistance in heart, skeletal muscle, renal and splanchnic circulations and with decreases in tissue blood flow in those regions at rest. Acute exercise caused a typical redistribution of blood flow, in which there was vasodilation in heart and working skeletal muscles, accompanied by vasoconstriction in kidney and splanchnic circulations. L-NA resulted in significantly elevated vascular resistance during vasodilation in heart and working skeletal muscles and also significantly increased vasoconstriction in renal cortex, stomach, pancreas, liver, and colon during exercise. Blood flows during exercise were largely unaffected by L-NA treatment. Our results suggest that whereas EDRF functions to regulate basal vascular tone and vascular resistance during exercise, EDRF has a minor role in determining the pattern of the redistribution of tissue blood flow during exercise.

Acetylcholine↗
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↗
PubMed1992

Phagolysosomal pH and dissolution of cobalt oxide particles by alveolar macrophages.

We studied phagolysosomal pH in rabbit alveolar macrophages (AM) incubated with 0-15 microM chloroquine. There was a dose-related increase in pH with chloroquine concentration. Electron microscopy showed that chloroquine increased lysosomal size. In a second experiment we studied dissolution of radiolabeled cobalt oxide particles by rabbit AM, phagolysosomal pH, and lysosomal size. The cells were incubated for 2 days with 0, 2.5, and 10 microM chloroquine. Size and pH increased with chloroquine concentration. Dissolution of cobalt particles by the AM did not clearly change with pH. In a third experiment, dissolution of cobalt oxide particles in 0.1 M acetate buffer in saline with pH 4.0, 5.0, and 6.0 was studied. At the same pH, dissolution in acetate buffer was faster than in the AM, and the dissolution appeared to decrease faster with increasing pH than in the AM. A simple model for dissolution of a particle in a phagolysosome was proposed. This model predicts the types of differences in dissolution between AM and buffered saline.

Animals↗
PubMed1991

[Lysozyme--an enzyme of both historical and current interest as a therapeutical agent].

Lysozyme, a bacteriolytic protein discovered by Fleming in 1922 and found to be phylogenetically ancient and almost ubiquitous among living organisms, is probably the most studied enzyme in biology and medicine. Evidence of its involvement in resistance to bacterial infection is compelling but remains indirect. Muramyl peptides (fragments of bacterial cell wall peptidoglycan) exert many effects on the immune system and the CNS, and appear to contribute to non-specific resistance to infection, fever, fatigue, and the pathogenesis of bacterial infection. Synthetic muramyl peptide analogues are currently used as adjuvants in vaccine trials in humans. Several pathological conditions are associated with changes in lysozyme concentrations, and egg-white lysozyme treatment has been tried on a small scale. With the cloning of the human lysozyme gene in yeast cells the enzyme can now be produced on a large scale, which will enable its therapeutic applications to be evaluated.

Bacterial Infections↗
PubMed1988

Alveolar macrophages in rabbits after combined exposure to nickel and trivalent chromium.

Rabbits were exposed to a combination of 0.7 mg/m3 Ni2+ as NiCl2 and 1.2 mg/m3 of Cr3+ as Cr(NO3)3, to 0.6 mg/m3 of Ni2+ as NiCl2, or to filtered air for about 4 months, 5 days/week and 6 hr/day. Alveolar macrophages were recovered by lung lavage and studied by light and electron microscopy. Metabolic activity, phagocytic capacity and lysozyme activity in the macrophages were studied. After the combined exposure, the effects on lung weight, number of macrophages, and appearance of surface and number of intracellular laminated inclusions in these cells were more than additive. These effects might be explained by a combination of increased production by Ni2+ and impaired catabolism of surfactant by Cr3+. Because the metal concentrations used were not far above occupational threshold limit values, combined exposures to nickel and trivalent chromium should be considered more seriously.

Animals↗
PubMed1987

Dissolution of two arsenic compounds by rabbit alveolar macrophages in vitro.

The ability of rabbit alveolar macrophages to dissolve two arsenic compounds, 74As-labeled lead arsenate and arsenic trisulfide, was studied in vitro. The solubilities in water of these two compounds are related differently to pH. The solubility of lead arsenate increases and that of arsenic trisulfide decreases with decreasing pH. The radiolabeled particles were incubated with and without macrophages for up to 3 days, whereafter the amount of 74As in soluble form and the amount in particle form and/or bound to macrophages were determined. The results strongly support the hypothesis that the dissolution of particles by macrophages is influenced by the acid milieu in the phagosomes. About 14% of the 74As-labeled lead arsenate particles incubated for 3 days with the macrophages was released into the culture medium, compared with about 2% of the particles incubated with the culture medium without macrophages. With the arsenic trisulfide particles, less soluble 74As was released into the medium in samples with macrophages than in samples without macrophages, although the solubility in all incubations was considerably greater than that for lead arsenate. The results indicate that dissolution in the phagosomes of the macrophages may be of great importance for the clearance of particles such as lead arsenate, which are more soluble at pH 4 than at pH 7.

Animals↗
PubMed1987

Fibronectin concentrations in lung lavage fluid after inhalation exposure to low levels of metals.

Groups of rabbits were exposed by inhalation to chlorides of cobalt, nickel, and manganese as well as to tri- and hexavalent chromium at metal concentrations ranging from 0.4 to 3.9 mg/m3 for 1-4 months (5 days/week, 6 hr/day). Fibronectin content and lysozyme (muramidase) activity in lavage fluid were measured after all treatments and in alveolar macrophages after treatment with nickel chloride. In the lavage fluid no marked changes were seen in fibronectin content and lysozyme activity after exposure to tri- or hexavalent chromium or manganese. Nickel exposure significantly decreased the lysozyme activity in the lavage fluid and in the macrophages whereas the fibronectin content was unchanged in the lavage fluid and significantly increased in the macrophages. Both fibronectin content and lysozyme activity were increased markedly in the lavage fluid after cobalt exposure.

Administration, Inhalation↗
PubMed1987

Lysozyme activity in ultrastructurally defined fractions of alveolar macrophages after inhalation exposure to nickel.

Rabbits were exposed to 0.6 mg/m3 of nickel as NiCl2 for about one month. After exposure, alveolar macrophages were lavaged from the lung and divided into three fractions by elutriation. Laminated structures in the macrophages were related to fraction number so that the fractions with the largest cells contained the highest number of structures. The lysozyme activity decreased in unfractionated as well as in fractionated macrophages from nickel exposed rabbits. The decrease was most pronounced in the fraction with the smallest macrophages and smallest number of laminated structures. Therefore the pronounced decrease in lysozyme activity seen in this and earlier studies is not caused by the increased amount of surfactant material. Increased amount of surfactant is a hallmark of nickel inhalation exposure and the surfactant material is responsible for the morphological and metabolic effects of the macrophages. The decreased lysozyme activity is probably a direct effect of nickel on the macrophages.

Animals↗
PubMed1986

Rabbit alveolar macrophages after long-term inhalation of soluble cobalt.

Rabbits were exposed to 2 or 0.4 mg/m3 of cobalt as CoCl2 for 14-16 weeks (5 days/week and 6 hr/day). More macrophages were lavaged from the lungs of rabbits exposed to the higher Co2+ concentration, and the diameter and variation of the diameter of the macrophages were significantly larger than in controls. The activity of lysozyme in the lavage fluid and in the macrophages was increased in the two exposed groups. Some macrophages in the exposed animals were large and engorged with intracellular lamellar inclusions and lipid droplets. Most of these cells had a smooth surface. The oxidative metabolic activity measured by reduction of nitroblue tetrazolium was increased in the exposed groups. The number of yeast cell particles attached to the surface of the macrophages was increased in the group exposed to the high concentration, but the number of ingested particles was not affected by cobalt exposure. Apart from the fact cobalt increased lysozyme activity whereas nickel decreased it, cobalt produced the same type of effects on macrophages as nickel did in earlier studies. Cobalt affected only a minor proportion whereas nickel affected most macrophages. This can be explained by the fact nickel produced a general increase in the volume density of the type II cells while cobalt affected the type II cells only in some areas of the lungs.

Administration, Inhalation↗