The Effect of Atmospheric Pollution on the Thymus

Air pollution is a high-risk factor in megacities’ dwellers because of its effects on health. One of the most important components of the pollution is particulate matter (PM) on which metals are adhered. One element adhered to its surfaces is vanadium (V), and through this route, PM reaches the respiratory system, then the systemic circulation and the rest of the organs. Vanadium is released in the atmosphere as a consequence of the combustion of fossil fuels. Vanadium pentoxide is the compound liberated after the combustion and adhered into PM. Previous studies from our group have reported effects on diverse systems in a mouse model. Besides the morphological changes in the spleen and the decreased function of the immune humoral response, the thymus was also affected. Vanadium inhalation diminished thymic dendritic cells (DCs) and the biomarkers: CD11c and MHCII; in addition, thymic cytoarchitecture changed, demonstrated by cytokeratin-5, and also, modification in the expression of 3-nitrotyrosine was observed. Our findings suggest that autoreactive T cells could be released into the systemic circulation and favor the increase in autoimmune diseases in cities with high concentrations of PM

Jak3 Is Involved in Dendritic Cell Maturation and CCR7-Dependent Migration

BACKGROUND: CCR7-mediated signalling is important for dendritic cell maturation and homing to the lymph nodes. We have previously demonstrated that Jak3 participates in the signalling pathway of CCR7 in T lymphocytes. METHODOLOGY AND PRINCIPAL FINDINGS: Here, we used Jak3(-/-) mice to analyze the role of Jak3 in CCR7-mediated dendritic cells migration and function. First, we found no differences in the generation of DCs from Jak3(-/-) bone marrow progenitors, when compared to wild type cells. However, phenotypic analysis of the bone marrow derived DCs obtained from Jak3(-/-) mice showed reduced expression of co-stimulatory molecules compared to wild type (Jak3(+/+)). In addition, when we analyzed the migration of Jak3(-/-) and Jak3(+/+) mature DCs in response to CCL19 and CCL21 chemokines, we found that the absence of Jak3 results in impaired chemotactic responses both in vitro and in vivo. Moreover, lymphocyte proliferation and contact hypersensitivity experiments showed that DC-mediated T lymphocyte activation is reduced in the absence of Jak3. CONCLUSION/SIGNIFICANCE: Altogether, our data provide strong evidence that Jak3 is important for DC maturation, migration and function, through a CCR7-mediated signalling pathway

Visualization and 3D Reconstruction of Flame Cells of Taenia solium (Cestoda)

BACKGROUND: Flame cells are the terminal cells of protonephridial systems, which are part of the excretory systems of invertebrates. Although the knowledge of their biological role is incomplete, there is a consensus that these cells perform excretion/secretion activities. It has been suggested that the flame cells participate in the maintenance of the osmotic environment that the cestodes require to live inside their hosts. In live Platyhelminthes, by light microscopy, the cells appear beating their flames rapidly and, at the ultrastructural, the cells have a large body enclosing a tuft of cilia. Few studies have been performed to define the localization of the cytoskeletal proteins of these cells, and it is unclear how these proteins are involved in cell function. METHODOLOGY/PRINCIPAL FINDINGS: Parasites of two different developmental stages of T. solium were used: cysticerci recovered from naturally infected pigs and intestinal adults obtained from immunosuppressed and experimentally infected golden hamsters. Hamsters were fed viable cysticerci to recover adult parasites after one month of infection. In the present studies focusing on flame cells of cysticerci tissues was performed. Using several methods such as video, confocal and electron microscopy, in addition to computational analysis for reconstruction and modeling, we have provided a 3D visual rendition of the cytoskeletal architecture of Taenia solium flame cells. CONCLUSIONS/SIGNIFICANCE: We consider that visual representations of cells open a new way for understanding the role of these cells in the excretory systems of Platyhelminths. After reconstruction, the observation of high resolution 3D images allowed for virtual observation of the interior composition of cells. A combination of microscopic images, computational reconstructions and 3D modeling of cells appears to be useful for inferring the cellular dynamics of the flame cell cytoskeleton

Ultrastructural glomerular changes in experimental infection with the classical swine fever virus

Ultrastructural studies of glomerular changes were performed on 16 pigs experimentally infected with a highly virulent strain of the classical swine fever virus. Our observations revealed the thickening of glomerular basement membranes, swelling of endothelial cells and cytoplasmic vacuolization within podocytes containing abundant viral particles. An early viral infection of podocytes was suggested as the cause of selective swelling of the foot processes of these cells with the consequent obliteration of the glomerular urinary spaces. To our knowledge this is the first report of ultrastructural evidence of classical swine fever virions infecting glomerular podocytes.Évolution de l'ultrastructure des glomérules rénaux lors d'une infection expérimentale par le virus de la peste porcine classique. Une étude en microscopie électronique des glomérules rénaux a été réalisée afin de mieux appréhender l'évolution de leur ultrastructure lors de l'atteinte rénale associée à la peste porcine classique. Les prélèvements ont été réalisés sur 16 porcelets infectés expérimentalement par une souche très virulente du virus de la fièvre porcine classique. Nos observations ont montré un épaississement de la membrane basale, une tuméfaction des cellules endothéliales associée à la présence de vacuoles dans le cytoplasme des podocytes. De nombreuses particules virales ont été observées dans le cytoplasme des podocytes. Une infection virale précoce des podocytes semble probable, et pourrait expliquer la tuméfaction spécifique de la protubérance podale de ces cellules, et par voie de conséquence, l'obstruction de l'espace urinaire glomérulaire. Actuellement, cette étude est la première à mettre en évidence par ultrastructure des particules virales de la peste porcine classique dans les podocytes glomérulaires

The Effect of Vanadium Inhalation on the Tumor Progression of Urethane-Induced Lung Adenomas in a Mice Model

Lung cancer has the highest death rates. Aerosol drug delivery has been used for other lung diseases. The use of inhaled vanadium (V) as an option for lung cancer treatment is explored. Four groups of mice were studied: (1) Saline inhalation alone, (2) Single intraperitoneal (i.p.) dose of urethane, (3) V nebulization twice a week (Wk) for 8 Wk, and (4) A single dose of urethane and V nebulization for 8 Wk. Mice were sacrificed at the end of the experiment. Number and size of tumors, PCNA (proliferating cell nuclear antigen) and TUNEL (terminal deoxynucleotidyl tranferase dUTP nick-end labeling) immunohistochemistry were evaluated and compared within groups. Results: The size and number of tumors decreased in mice exposed to V-urethane and the TUNEL increased in this group; differences in the PCNA were not observed. Conclusions: Aerosol V delivery increased apoptosis and possibly the growth arrest of the tumors with no respiratory clinical changes in the mice

Air Pollution and Retained Particles in the Lung

Epidemiologic evidence associates particulate air pollution with cardiopulmonary morbidity and mortality. The biological mechanisms underlying these associations and the relationship between ambient levels and retained particles in the lung remain uncertain. We examined the parenchymal particle content of 11 autopsy lungs from never-smoking female residents of Mexico City, a region with high ambient particle levels [3-year mean PM₁₀ (particulate matter ≤ 10 μm in aerodynamic diameter)= 66 μg/m³], and 11 control residents of Vancouver, British Columbia, Canada, a region with relatively low levels (3-year mean PM₁₀ = 14 μg/m³). Autopsy lungs were dissolved in bleach and particles were identified and counted by analytical electron microscopy. Total particle concentrations in the Mexico City lungs were significantly higher [geometric mean = 2,055 (geometric SD = 3.9) × 10⁶ particles/g dry lung vs. 279 (1.8) × 10⁶ particles/g dry lung] than in lungs from Vancouver residents. Lungs from Mexico City contained numerous chain aggregated masses of ultrafine carbonaceous spheres, some of which contained sulfur, and aggregates of ultrafine aluminum silicate. These aggregates made up an average of 25% of the total particles by count in the lungs from Mexico City, but were only rarely seen in lungs from Vancouver. These observations indicate for the first time that residence in a region with high levels of ambient particles results in pulmonary retention of large quantities of fine and ultrafine particle aggregates, some of which appear to be combustion products.Medicine, Department ofMedicine, Faculty ofOccupational and Environmental Hygiene, School ofPathology and Laboratory Medicine, Department ofNon UBCReviewedFacult

Thymic cytoarchitecture changes in mice exposed to vanadium

The thymus is a vital immune system organ wherein selection of T-lymphocytes occurs in a process regulated by dendritic and epithelial thymic cells. Previously, we have reported that in a mouse model of vanadium inhalation, a decrease in CD11c dendritic cells was observed. In the present study, we report on a thymic cortex–medulla distribution distortion in these hosts due to apparent effects of the inhaled vanadium on cytokeratin-5 (K5+) epithelial cells in the same mouse model – after 1, 2, and 4 weeks of exposure – by immunohistochemistry. These cells – together with dendritic cells – eliminate autoreactive T-cell clones and regulate the production of regulatory T-cells in situ. Because both cell types are involved in the negative selection of autoreactive clones, a potential for an increase in development of autoimmune conditions could be a possible consequence among individuals who might be exposed often to vanadium in air pollution, including dwellers of highly polluted cities with elevated levels of particulate matter onto which vanadium is often adsorbed

Chronic Exposure to High Levels of Particulate Air Pollution and Small Airway Remodeling

Recent evidence suggests that chronic exposure to high levels of ambient particulate matter (PM) is associated with decreased pulmonary function and the development of chronic airflow obstruction. To investigate the possible role of PM-induced abnormalities in the small airways in these functional changes, we examined histologic sections from the lungs of 20 women from Mexico City, a high PM locale. All subjects were lifelong residents of Mexico City, were never-smokers, never had occupational dust exposure, and never used biomass fuel for cooking. Twenty neversmoking, non–dust-exposed subjects from Vancouver, British Columbia, Canada, a low PM region, were used as a control. By light microscopy, abnormal small airways with fibrotic walls and excess muscle, many containing visible dust, were present in the Mexico City lungs. Formal grading analysis confirmed the presence of significantly greater amounts of fibrous tissue and muscle in the walls of the airways in the Mexico City compared with the Vancouver lungs. Electron microscopic particle burden measurements on four cases from Mexico City showed that carbonaceous aggregates of ultrafine particles, aggregates likely to be combustion products, were present in the airway mucosa. We conclude that PM penetrates into and is retained in the walls of small airways, and that, even in nonsmokers, long-term exposure to high levels of ambient particulate pollutants is associated with small airway remodeling. This process may produce chronic airflow obstruction.Occupational and Environmental Hygiene, School ofPathology and Laboratory Medicine, Department ofPopulation and Public Health (SPPH), School ofNon UBCMedicine, Faculty ofReviewedFacult