Biomedical subjects

Ernesto Alfaro-Moreno

Publications and source records attributed to Ernesto Alfaro-Moreno.

4 recordsLinked to original sources

PubMed2006

Relations between PM10 composition and cell toxicity: a multivariate and graphical approach.

Previous studies have used particle mass and size as metrics to link airborne particles with deleterious health effects. Recent evidence suggests that particle composition can play an important role in PM-toxicity; however, little is known about the specific participation of components (individually or acting in groups) present in such a complex mixture that accounts for toxicity. This work explores relationships among PM(10) components in order to identify their covariant structure and how they vary in three sites in Mexico City. Relationships between PM(10) with cell toxicity and geographical location were also explored. PM(10) was analyzed for elemental composition, organic and elemental carbon, endotoxins and the induction of inhibition of cell proliferation, IL-6, TNFalpha and p53. PM(10) variables were evaluated with principal component analysis and one-way ANOVA. The inhibition of cell proliferation, IL-6 and TNFalpha were evaluated with factorial ANOVA and p53 with the Welch test. The results indicate that there is heterogeneity in particle mass, composition and toxicity in samples collected at different sites. Multivariate analysis identified three major groups: (1) S/K/Ca/Ti/Mn/Fe/Zn/Pb; (2) Cl/Cr/Ni/Cu; and (3) endotoxins, organic and elemental carbon. Groups 1 and 3 showed significant differences among sites. Factorial ANOVA modeling indicated that cell proliferation was affected by PM concentration; TNFalpha and IL-6 by the interaction of concentration and site, and p53 was different by site. Radial plots suggest the existence of complex interactions between components, resulting in characteristic patterns of toxicity by site. We conclude that interactions of PM(10) components determine specific cellular outcomes.

Air Pollutants↗

PubMed2006

E-Selectin expression in human endothelial cells exposed to PM10: the role of endotoxin and insoluble fraction.

Exposure to PM10 is associated with cardiovascular effects. We evaluated the effects of PM10 on E-Selectin expression and monocytic cell adhesion in human umbilical vein endothelial cells (HUVECs). HUVEC were exposed to PM10 (5-40 microg/cm2) for 6 h, following which surface E-Selectin expression was detected by fluorescence microscopy and flow cytometry. The effects of total particles, particles treated with polymixin-B to block the effects of endotoxin, and both soluble and insoluble fractions of particles, were assessed. Incubation with PM10 lead to a concentration-related increase of E-Selectin expression (>seven-fold increase at 40 microg/cm2). Particles pre-treated with polymixin-B inhibited E-Selectin expression to a level slightly higher than untreated particles. An increase in fluorescence was also observed with the insoluble fraction, while the soluble fraction had no significant effect. HUVEC exposed to PM10 were also evaluated for adhesivity of monocytic cells (U937). PM10 strongly increased the adhesion of U937 cells to HUVEC. In conclusion, PM10 induces endothelial cell activation, evidenced by enhanced E-Selectin expression. This activation is manifested functionally as an increase in monocytic cell adhesion. Insoluble components as well as endotoxins appear to be responsible for this activity.

Cell Adhesion↗

PubMed2003

Proinflammatory and cytotoxic effects of Mexico City air pollution particulate matter in vitro are dependent on particle size and composition.

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.

Air Pollutants↗

PubMed2002

Biologic effects induced in vitro by PM10 from three different zones of Mexico City.

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.

Air Pollutants↗