RESUMO
Vanadium (V) is a transition metal found in air adsorbed onto suspended particles. As a result, urban populations are often exposed to this element as a constituent of particulate matter (PM). One aspect of the myriad toxicities that might arise from these exposures is altered immune responses. Previous reports from the laboratory reported modifications in splenic architecture - with germinal center hyperplasia and a suppressed humoral immune response - in mice that had been exposed to vanadium agents via inhalation. This paper reports a decrease in the presence of the CD11c surface marker on mouse thymic dendritic cells (DC) as a result of host exposure to vanadium (here, in the form of vanadium pentoxide; V(2)O(5)) over a period of 4 weeks. All results were obtained using immunohistochemistry and flow cytometry. It is surmised that this decrease might induce a dysfunction, including possible negative selection of T-cells, which could increase the presence of autoreactive clones in the exposed host. Such an outcome could, in turn, increase the risk for development of autoimmune reactions in different organs specifically, and of autoimmune diseases in general in these V-exposed hosts.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Doenças Autoimunes/etiologia , Antígeno CD11c/imunologia , Células Dendríticas/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Timo/efeitos dos fármacos , Vanádio/efeitos adversos , Animais , Doenças Autoimunes/imunologia , Separação Celular , Células Cultivadas , Células Dendríticas/imunologia , Regulação para Baixo , Citometria de Fluxo , Inalação , Masculino , Camundongos , Camundongos Endogâmicos , Timo/imunologiaRESUMO
Vanadium, an important air pollutant derived from fuel product combustion, aggravates respiratory diseases and impairs cardiovascular function. In contrast, its effects on immune response are conflicting. The aim of our work was to determine if spleens of vanadium-exposed CD1 mice showed histological lesions that might result in immune response malfunction. One hundred and twelve CD-1 male mice were placed in an acrylic box and inhaled 0.02 M vanadium pentoxide (V2O5); actual concentration in chamber approximately 1.4 mg V2O5/m(3)) for 1 hr/d, twice a week, for 12 wk. Control mice inhaled only vehicle. Eight mice were sacrificed prior to the exposures. Eight control and eight V2O5-exposed mice were sacrificed 24 hr after the second exposure of each week until the 12-wk study was over. Another 8 mice that completed the 12-wk regimen were immunized with recombinant Hepatitis B surface antigen (HBsAg; three times over an 8-wk period) before sacrifice and analyses of their levels of anti-HBsAg antibody (HBSAb) using ELISA. In all studies, at sacrifice, blood samples were obtained by direct heart puncture and the spleen was removed, weighed and processed for H-E staining and quantitation of CD19 cells. The results indicated that the spleen weight of V2O5-exposed animals peaked at 9 wk (546 +/- 45 vs. 274 +/- 27 mg, p < 0.0001) and thereafter progressively decreased (321 +/- 39 mg at 12 wk, p < 0.001; control spleen = 298 +/- 35 mg). Spleens of V2O5-exposed animals showed an increased number of very large and non-clearly delimited germinal centers (that contained more lymphocytes and megakaryocytes) compared to those of control mice. In addition, their red pulp was poorly delimited and had an increase in CD19+ cells within hyperplasic germinal nodes. The mean HBsAb levels in immunized control mice were greater than that in the exposed hosts (i.e., OD = 0.39 +/- 0.03 vs. 0.11 +/- 0.05, p < 0.01). HBsAb avidity dropped to a value of 40 in V2O5-exposed animals vs. 86 in controls (p < 0.0001). We conclude that the chronic inhalation of V2O5, a frequent particle (PM(2.5)) component, induces histological changes and functional damage to the spleen, each of which appear to result in severe effects on the humoral immune response.
Assuntos
Poluentes Atmosféricos/toxicidade , Formação de Anticorpos/efeitos dos fármacos , Centro Germinativo/imunologia , Exposição por Inalação/efeitos adversos , Baço/imunologia , Compostos de Vanádio/toxicidade , Animais , Formação de Anticorpos/imunologia , Antígenos CD19/imunologia , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/patologia , Centro Germinativo/patologia , Anticorpos Anti-Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/administração & dosagem , Hiperplasia/induzido quimicamente , Hiperplasia/imunologia , Hiperplasia/patologia , Imunização , Linfócitos/imunologia , Linfócitos/patologia , Masculino , Megacariócitos/imunologia , Megacariócitos/patologia , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Tamanho do Órgão/imunologia , Doenças Respiratórias/induzido quimicamente , Doenças Respiratórias/imunologia , Doenças Respiratórias/patologia , Baço/patologia , Fatores de TempoRESUMO
Vanadium (V) derivatives are well-known environmental pollutants and its toxicity has been related with oxidative stress. Toxicity after vanadium inhalation on the substantia nigra, corpus striatum, hippocampus and ependymal epithelium was reported previously. The purpose of this study was to analyse the role of matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9) in the changes observed in brain tissue after chronic V inhalation. Mice were exposed to vaporized, vanadium pentoxide 0.02 m in deionized water for 1 h twice a week, and killed at 1 h, 1, 2 and 4 weeks after exposure. The brain was removed and the olfactory bulb, prefrontal cortex, striatum and hippocampus were dissected and the MMP content was obtained by zymography. The results showed that MMP-9 increased in all the structures at the end of the exposure, although in the hippocampus this increment was evident after 1 week of exposure. When MMP-2 was analysed in the olfactory bulb and prefrontal cortex it remained unchanged throughout the whole exposure, while in the hippocampus it increased at week 4, while in the striatum MMP-2 increased from the second week only, through the whole experiment. These results demonstrate that V increased MMPs in different structures of the CNS and this change might be associated with the previously reported modifications, such as dendritic spine loss and neuronal cell death. The modifications in MMPs could be related with blood-brain barrier (BBB) disruption which was reported previously. Oxidative stress might also be involved in the activation of these gelatinases as part of the different mechanisms which take place in V toxicity in the CNS.