Epidemiological and clinical studies have linked exposure to particulate matter (PM) to adverse health effects, which may be registered as increased mortality and morbidity from various cardiopulmonary diseases. Despite the evidence relating PM to health effects, the physiological, cellular, and molecular mechanisms causing such effects are still not fully characterized. Two main approaches are used to elucidate the mechanisms of toxicity. One is the use of in vivo experimental models, where various effects of PM on respiratory, cardiovascular, and nervous systems can be evaluated. To more closely examine the molecular and cellular mechanisms behind the different physiological effects, the use of various in vitro models has proven to be valuable. In the present review, we discuss the current advances on the toxicology of particulate matter and nanoparticles based on these techniques.

Exposure to urban airborne particulate matter (PM) is associated with adverse health effects. We previously reported that the cytotoxic and proinflammatory effects of Mexico City PM10 (less than or equal to 10 micro m mean aerodynamic diameter) are determined by transition metals and endotoxins associated with these particles. However, PM2.5 (less than or equal to 2.5 micro m mean aerodynamic diameter) could be more important as a human health risk because this smaller PM has the potential to reach the distal lung after inhalation. In this study, we compared the cytotoxic and proinflammatory effects of Mexico City PM10 with those of PM2.5 using the murine monocytic J774A.1 cell line in vitro. PMs were collected from the northern zone or the southeastern zone of Mexico City. Elemental composition and bacterial endotoxin on PMs were measured. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) production by J774A.1 cells was measured in the presence or absence of recombinant endotoxin-neutralizing protein (rENP). Both northern and southeastern PMs contained endotoxin and a variety of transition metals. Southeastern PM10 contained the highest endotoxin levels, 2-fold higher than that in northern PM10. Northern and southeastern PM2.5 contained the lowest endotoxin levels. Accordingly, southeastern PM10 was the most potent in causing secretion of the proinflammatory cytokines TNF-alpha and IL-6. All PM2.5 and PM10 samples caused cytotoxicity, but northern PMs were the most toxic. Cytokine secretion induced by southeastern PM10 was reduced 50-75% by rENP. These results indicate major differences in PM10 and PM2.5. PM2.5 induces cytotoxicity in vitro through an endotoxin-independent mechanism that is likely mediated by transition metals. In contrast, PM10 with relatively high levels of endotoxin induces proinflammatory cytokine release via an endotoxin-dependent mechanism.

Exposure to urban airborne particles is associated with an increase in morbidity and mortality. There is little experimental evidence of the mechanisms involved and the role of particle composition. We assessed cytotoxicity (crystal violet assay), apoptosis [terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) or annexin V assay], DNA breakage (comet assay), and production of proinflammatory mediators [tumor necrosis factor Alpha (TNF-Alpha), interleukin 6 (IL-6), prostaglandin E2 (PGE2)] (enzyme-linked immunosorbent assay), and E-selectin (flow cytometry) in cell lines exposed to particulate matter < 10 microm in size (PM10) obtained from the northern, central, and southern zones of Mexico City. Particle concentrations ranged from 2.5 to 160 microg/cm(2). We used epithelial, endothelial, fibroblastic, and monocytic cells and assessed DNA damage in Balb-c cells, TNF-Alpha and IL-6 production in mouse monocytes, and PGE2 in rat lung fibroblasts. We determined the expression of E-selectin in human endothelial cells and evaluated the cytotoxic potential of the PM10 samples in all cell types. PM10 from all three zones of Mexico City caused cell death, DNA breakage, and apoptosis, with particles from the north and central zones being the most toxic. All of these PM10 samples induced secretion of proinflammatory molecules, and particles from the central zone were the most potent. Endothelial cells exposed to PM10 from the three zones expressed similar E-selectin levels. Mexico City PM10 induced biologic effects dependent on the zone of origin, which could be caused by differences in the mixture or size distribution within particle samples. Our data suggest that particle composition as well as particle size should be considered in assessing the adverse effects of airborne particulate pollution.

There have been several studies of the relationships between environmental factors, particularly air pollution, and attacks of asthma. Most of these studies have ignored the potential confounding effects of aeroallergens such as pollens and fungal spores. We report a statistical analysis of the relationships between emergency admissions for asthma to a hospital in Mexico City and daily average airborne concentrations of pollen, fungal spores, air pollutants (O3, NO2, SO2, and particulates) and weather factors. Asthma admissions had a seasonal pattern with more during the wet season (May-October) than the dry season (November-April). There were few statistical associations between asthma admissions and air pollutants for the three age groups studied (children under 15 years, adults, and seniors [adults over 59 years]) in either season. Grass pollen was associated with child and adult admissions for both the wet and dry seasons, and fungal spores were associated with child admissions during both the wet and dry seasons. The analysis was done with environmental data averaged over the day of admission and the 2 previous days. Our results suggest that aeroallergens may be statistically associated more strongly with asthma hospital admissions than air pollutants and may act as confounding factors in epidemiologic studies.

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