ISSN:0894-2684    

DOI:10.1089/jam.1990.3.Suppl_1.S-1

年代:1990

数据来源: MAL

ISSN:0894-2684    

DOI:10.1089/jam.1990.3.Suppl_1.S-3

年代:1990

数据来源: MAL

摘要:

ABSTRACTAlveolar macrophage (AM)-mediated particle clearance from the lung via the conducting airways is an important mechanism by which relatively insoluble particles are translocated from the alveolar region. Diminution in the kinetics of removal of particles from the lung following the deposition of excessive particulate lung burdens (particle "overload"), which can be functionally viewed as the emergence of a sequestration compartment(s), suggests AM-related bases inasmuch as these cells are usually the primary reservoirs of deposited particles. Specific details about the mechanisms involved in AM-mediated lung clearance or about processes that may favor particle retention in the lung have not been well delineated. In the present investigation, the retention kinetics of a low to a relatively high lung burden of uniform polystyrene microspheres was examined with the highest burden studied resulting in a condition of particle "overload". We also assessed the lung's free cell response to these burdens over a prolonged period following the intrapulmonary deposition of the particles as we concurrently investigated particle-AM relationships during the alveolar clearance of the different lung burdens. Evidence obtained suggests the particles were gradually redistributed among members of the lung's free cell population of phagocytes during alveolar clearance. Additionally, polymorphonuclear leukocytes and blood monocyte-, pulmonary interstitial macrophage-like cells became increasingly prominent in the lung's free cell population over time during a condition of particle overload with the polystyrene microspheres; such findings suggest that these cells may potentially play a pathogenic role when lung burdens are excessive. Electron microscopic analyses suggested that aggregates of particle-laden macrophages, particle-containing Type I pneumocytes, and particle-containing pulmonary interstitial macrophages represent particle sequestration sites that contribute to diminished lung clearance during particle overload. However, our analyses of particle-AM relationships during particle overload point to AM with paniculate volume loads equal to or in excess of 60% of their normal volumes as being the main sequestrating compartment to which diminished rates of lung clearance can be virtually totally attributed. Moreover, the size of the AM-particle sequestering compartment appeared to remain stable over a 5 month period after the particles were deposited in the lungs. This latter observation suggests that once developed, the AM-particle sequestration compartment is essentially irreversibly maintained.

ISSN:0894-2684    

DOI:10.1089/jam.1990.3.Suppl_1.S-9

年代:1990

数据来源: MAL

摘要:

ABSTRACTInstillation of carbon into mouse lung results in a rapid increase in cells recovered by bronchoalveolar lavage. Initially the increase is due to polymorphonuclear leukocytes (PMN), then after 12 hours, alveolar macrophage (AM) numbers increase and reach a maximum at 2-3 days. Whereas the initial increase in AM is due to migration of monocyte-derived cells, after 1 day AM numbers are maintained by proliferation and migration of interstitial cell precursors. In a particle overload situation, the number of AM recovered at 1 day peaked with a 1.0 mg dose and did not increase as the dose was raised though the duration of the maximal response was extended. At high levels, translocation of particles into lung parenchyma was seen and carbon was found in Type 1 epithelial cells, in interstitial macrophages (IM) and in hilar lymph nodes. An alveolar overload situation was induced by reducing phagocytosis and clearance. We instilled carbon to the lungs of mice depleted of leukocytes by whole body irradiation. The usual eflux of PMN and AM was delayed and reduced, leading to greater particle transfer to the interstitium and lymph nodes than after carbon alone. When silica was injected to irradiated mice, the increase in PMN and AM was reduced, and many particles reached the IM. At 16 weeks radiated mice that received silica had a higher weight of retained particles in the lungs, and collagen measurements were much higher than after silica or irradiation alone. The results suggest that alveolar overload greatly enhances particle translocation to the interstitium where secretion of any macrophage-derived factors is more likely to be effective in fibroblast stimulation.

ISSN:0894-2684    

DOI:10.1089/jam.1990.3.Suppl_1.S-31

年代:1990

数据来源: MAL

摘要:

Alveolar macrophages recovered by bronchoalveolar lavage from individuals with occupational inorganic dust exposure are laden with particles. We evaluated 42 non-smoking males with long-term exposure to asbestos (27), coal (7), or silica (8), and normals (8) to determine a particle burden per 106alveolar macrophages. Scanning/transmission electron microscopy and energy-dispersive x-ray analysis were utilized to evaluate the particles following bleach digestion of the cells, or of alveolar macrophage sections. There was a four-fold (p<0.01) increase in the number of particles in the dust-exposed. There was also a striking increase in silica particle number in the silica-exposed (p<0.02) but not in the other dust-exposed groups. One-third of the coal miner's cells contained silica particles predominantly<0.5 μm. In the asbestos-exposed, there was one chrysotile fiber per 35 cells, and one amosite fiber per 215 cells consistent with the known mixed exposure of workers exposed to insulation products in the United States. No crocidolite was observed in any of the cells and tremolite was identified in two controls and two workers. Computer-generated maps of elements comprising the particles demonstrated the in situ localization of the particles and identified many very small alumino-silicates, particularly in coal miners. Particle analysis is a useful technique to evaluate type and amount of exposure, to evaluate alveolar clearance, and may be useful to investigate macrophage activation

ISSN:0894-2684    

DOI:10.1089/jam.1990.3.Suppl_1.S-43

年代:1990

数据来源: MAL

ISSN:0894-2684    

DOI:10.1089/jam.1990.3.Suppl_1.S-57

年代:1990

数据来源: MAL

ISSN:0894-2684    

DOI:10.1089/jam.1990.3.Suppl_1.S-61

年代:1990

数据来源: MAL

摘要:

ABSTRACTSeveral studies suggest that active oxygen species (AOS) are involved in the development of asbestos-induced lung diseases. Experiments in this laboratory have focused on antioxidant enzymes as preventive agents of asbestosinduced cell injury when added to cultures of alveolar macrophages (AMs), tracheobronchial epithelial cells, the progenitor cells of lung cancer (bronchogenic carcinoma), and lung fibroblasts, a cell type affected in asbestosis. Most recently, lung injury, inflammation, and pulmonary fibrosis have been ameliorated in an inhalation model of asbestosis using administration of antioxidant enzymes to rats during their exposure to asbestos. Current studies are focusing on the patterns and mechanisms of induction of antioxidant enzymes in the lung after inhalation of asbestos. These studies indicate that levels of antioxidant enzymes [total Superoxide dlsmutase (SOD), glutathione peroxidase (GPX), catalase] are increased in lungs within days after the initiation of exposure to high airborne concentrations (~ 7 mg/m3air) of crocidolite asbestos. Use of cDNA probes for CuZn and Mn-containing SODs indicates that steady-state mRNA levels of Mn-SOD are increased in the lungs of asbestos-exposed animals, while CuZn-SOD expression is unchanged. Results suggest that inhalation of crocidolite asbestos induces increased expression of an antioxidant enzyme in lung which is induced by cytokines such as interleukin-1 (IL-1) and tumor necrosis factor α (TNF) in a variety of cell types

ISSN:0894-2684    

DOI:10.1089/jam.1990.3.Suppl_1.S-75

年代:1990

数据来源: MAL

摘要:

ABSTRACTThis report summarizes recent findings on the relationships among overloaded lung clearance, activation of alveolar macrophages (AM) release of inflammatory mediators and the development of fibrosis using Ti02 as a model nuisance type dust. Briefly rats were intratracheally instilled with 2-100 mg Ti02/kg body weight and AM tumor necrosis factor or fibronectin release determinedex vivo1, 7, 14 and 28 days after exposure. Lung dust burdens were determined 1 and 28 days after exposure. Histopathology was assessed 28 and 90 days after exposure. Intratracheal instillation of ≥50 mg/kg Ti02 resulted in overloaded lung clearance. Ti02 doses ≥50 mg/kg stimulated transient increases in AM TNF release and a persistent increase in AM fibronectin secretion. Histopathology demonstrated dose-related interstitial inflammation with fibrosis developing only after treatment with ≥50 mg/kg Ti02. Results from these studies suggest activation of AM secretory activity may play a key role in adverse pulmonary responses to high dust burdens of relatively innocuous materials. Studies investigatingin vitroresponses of AM to dust indicated that direct Ti02:AM interaction does not stimulate release of TNF or fibronectin, however, pre-exposure to γ-interferon can render AM responsive to Ti02 with respect to increased TNF r

ISSN:0894-2684    

DOI:10.1089/jam.1990.3.Suppl_1.S-83

年代:1990

数据来源: MAL

摘要:

ABSTRACTLung clearance studies after the inhalation of monodisperse, radiolabelled test particles including lung retention measurements and excretion analysis allow for estimates of the kinetics of long-term particle transport out of the thorax into the gastro-intestinal tract. Data of several interspecies comparisons using either radiolabelled fused aluminosilicate particles or57C03O4particles were reviewed and compared. Species included were: man, baboon, beagle dog, guinea pig, HMT rat, F-344 rat, Long-Evans rat, hamster, mouse.Particle transport M(t) after the first days after inhalation is a slow clearance mechanism which is independent of the particle material and size used (0.5 - 4 pirn geom. diameter). M(t) was reproducible in the experimental species studied. In man, baboon, and dog the initial daily fraction M0of the contemporary lung burden transported out of the thorax is 0.001 d-1which is an order of magnitude less than the initial rates in rodents. Particle transport rate decreases rapidly from its initial value in all species studied. The decay of particle transport varies considerably between the species and strains. The half-life of the decreasing transport rate is slower in man, dog, F-344 rat, hamster and mouse (100 - 200 days) than in baboon, HMT rat and Long-Evans rat (<50 days). From these studies estimates of lung retention during chronic aerosol exposure showed no equilibrium value indicating that long-term particle transport is not a sufficiently effective clearance mechanism to keep the lung burden from continuousy increasing during chronic exposure.

ISSN:0894-2684    

DOI:10.1089/jam.1990.3.Suppl_1.S-93

年代:1990

数据来源: MAL