RESUMEN
There is conflicting evidence in the literature as to the predominant mechanism and also the compositional element(s) that drives the pulmonary inflammatory response of ambient particulate matter (PM). We have investigated the inflammogenic potential of coarse (2.5-10 microm) and fine (<2.5 microm) PM from both a rural and an industrial location in Germany, using bronchoalveolar lavage (BAL) of rat lungs 18 h post intratracheal instillation with PM. Irrespective of the sampling location, the coarse fraction of PM(10) but not its fine counterpart caused neutrophilic inflammation in rat lungs, in the absence of any severe pulmonary toxicity as indicated by the lack of an increase in lavage protein and lactate dehydrogenase levels. The rural sample of coarse PM also caused a significant increase in the tumor necrosis factor alpha (TNFalpha) content as well as glutathione depletion in the BAL fluid. The contrasting inflammatory responses of the different samples could not be explained by differences in the concentrations of soluble Fe, Cu, V, Ni, Cr, or Al or by the.OH generating capacities of the PM suspensions. However, the effects of the different PM samples were clearly associated with their endotoxin content, as well as their ability to induce interleukin (IL)-8 and TNFalpha from whole blood in vitro. In conclusion, on an equal mass basis, coarse but not fine PM samples from our sampling campaign induced an inflammatory reaction in the lung in the absence of gross cellular lung damage, following intratracheal instillation. Our data also indicate, in accordance with previous independent in vitro observations, that endotoxin or related contaminants may play a role in these in vivo effects.
Asunto(s)
Contaminantes Atmosféricos/toxicidad , Pulmón/efectos de los fármacos , Neumonía/metabolismo , Contaminantes Atmosféricos/química , Animales , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Endotoxinas/aislamiento & purificación , Femenino , Alemania , Glutatión/análisis , Radical Hidroxilo/aislamiento & purificación , Instilación de Medicamentos , Interleucina-8/sangre , L-Lactato Deshidrogenasa/análisis , Recuento de Leucocitos , Pulmón/metabolismo , Metales Pesados/aislamiento & purificación , Neutrófilos/citología , Tamaño de la Partícula , Neumonía/sangre , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The adverse health effects of elevated exposures to PM(10) (particulate matter collected through a size selective inlet with an efficiency of 50% for particles with an aerodynamic diameter of 10 µm) in relation to morbidity and mortality, especially in susceptible individuals, are now well recognised. PM(10) consists of a variable cocktail of components differing in chemical composition and size. Epidemiological and toxicological data suggest that transition metals and ultrafine particles are both able to drive the cellular and molecular changes that underlie PM(10)-induced inflammation and so worsen disease status. Toxicological evidence also suggest roles for the biological components of PM(10) including volatile organic compounds (VOC's), allergens and bacterial-derived endotoxin. Many of these components, in particular transition metals, ultrafine particles, endotoxin and VOC's induce a cellular oxidative stress which initiates an intracellular signaling cascade involving the activation of phosphatase and kinase enzymes as well as transcription factors such as nuclear factor kappa B. Activation of these signaling mechanisms results in an increase in the expression of proinflammatory mediators, and hence enhanced inflammation. Given that many of the components of PM(10) stimulate similar or even identical intracellular signaling pathways, it is conceivable that this will result in synergistic or additive interactions so that the biological response induced by PM(10) exposure is a response to the composition rather than the mass alone. A small number of studies suggest that synergistic interactions occur between ultrafine particles and transition metals, between particles and allergens, and between particles and VOC's. Elucidation of the consequences of interaction between the components of PM(10) in relation to their biological activity implies huge consequences for the methods used to monitor and to legislate pollution exposure in the future, and may drive a move from mass based measurements to composition.
RESUMEN
Both the ultrafine particle and transition metal components of particulate air pollution (PM(10)) have been hypothesized to be important factors in determining toxicity and potential adverse health effects. In this study we aimed to investigate interactions between transition metal salts and a surrogate environmental particle-ultrafine carbon black (ufCB). In all experimental systems employed, the ufCB was found to be more reactive than its fine counterpart (CB). Incubation of ufCB with the reactive oxygen species (ROS)-sensitive probe dichlorofluorescin in the absence of cells generated significantly more ROS than CB. With addition of either cupric sulfate (CuSO(4)), ferrous sulfate (FeSO(4)), or ferric chloride (FeCl(3)), the ROS generation in the presence of ufCB was enhanced in a potentiative manner. In Mono Mac 6 macrophages, ufCB again produced more ROS than CB. However, addition of iron salts had no additive effect over and above that induced in the macrophages by ufCB. In the mouse macrophage cell line J774, ufCB decreased the cellular content of GSH and ATP. Addition of iron further decreased both GSH and ATP and a potentiative interaction between ufCB and FeSO(4) was observed, but only at the highest iron concentrations tested. A concentration-dependent increase in tumor necrosis factor-alpha production by J774 cells was also observed following exposure to ufCB, which was not further enhanced by the addition of iron. J774 cells were also found to sequester or chelate iron without inducing toxicity. In the rat lung ufCB induced a significant neutrophil influx and this inflammatory effect was potentiativelly enhanced by the addition of FeCl(3) (100 microM). These findings suggest that (1) ultrafine particles and metals interact by chemical potentiation in a cell-free environment to generate ROS, (2) potentiation between ultrafine particles and metal salts is not observed in the presence of macrophages as iron is sequestered or chelated by the cells, (3) in the lung, ultrafine particles and iron salts interact in a potentiative manner to generate inflammation.