Iron release and ROS generation from mineral particles are not related to cytokine release or apoptosis in exposed A549 cells.

The generation of reactive oxygen species (ROS) by mineral particles is believed to be central to their toxicity and their ability to induce inflammation. Surface bound or soluble iron may contribute to the particle-effects by enhancing the ROS generation through the Fenton reaction. Nevertheless, the importance of ROS and transition metals to mineral particle-induced effects is still unclear and further investigations are needed. In the present study we have investigated different mineral particles for their total iron content, amount of soluble iron at pH 7.0 and 4.0, their ability to generate ROS in a cell-free environment, and their ability to induce cytokine release and apoptosis in a human alveolar epithelial cell line (A549). All the investigated parameters varied considerably between the different particles, with the exception of ability to induce apoptosis. Total iron content did not reflect the amount of soluble iron, and neither total nor soluble iron was correlated with ROS generation. Moreover, iron content and ROS was not correlated with the ability of particles to induce cytokine release or apoptosis. The present results suggest that there is no clear relationship between the particles iron content and ability to generate ROS. Moreover, neither iron content nor the ability to induce ROS generation appears to be a prerequisite for the inflammatory potential or cytotoxicity of mineral particles.

Mineral and/or metal content as critical determinants of particle-induced release of IL-6 and IL-8 from A549 cells.

Mineral particles in occupational exposure and ambient air particles may cause adverse health effects in humans. In this study the ability of different stone quarry particles to induce release of the proinflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) from human epithelial lung cells (A549) was investigated. Size distribution within the PM10 fractions was quite similar for all particle samples, whereas mineral content and metal composition differed. Particles, containing minerals such as quartz, amphibole, chlorite, and epidote, induced a marked increase in IL-6 and IL-8 release. Particles composed mainly of plagioclase were much less effective. The most potent particle samples exhibited a relatively high content of transition metals such as iron. Exposure to identical masses or surface areas resulted in the same order of potency among the different particle samples. Significant cytotoxicity was observed only at higher concentrations of particle exposure. Thus, mineral composition and/or metal contents of particles from different stone quarries were critical determinants for the marked differences in potency to induce cytokine responses in human epithelial lung cells.

Silica-induced cytokine release from A549 cells: importance of surface area versus size.

Physical and chemical properties such as structure, composition and surface reactivity determine the biological activity of mineral particles. Long-term exposure to crystalline silica is known to cause persistent pulmonary inflammation leading to adverse health effects. There is less information about the potential health effects of amorphous (noncrystalline) silica. In this study, the inflammatory and cytotoxic potency of crystalline and amorphous silica in relation to particle size and surface area was assessed. Human epithelial lung cells (A549) were exposed to different size fractions of quartz ( aerodynamic diameter 0.5, 2 and 10 microm) and amorphous silica (diameter 0.3 microm). All particles induced increased release of the proinflammatory cytokines interleukin (IL)-6 and IL-8. When cells were exposed to equal masses of quartz, the smallest size fraction was the most potent. These differences, however, disappeared when cytokine release was related to equal surface areas. When amorphous silica and quartz were compared, the amorphous silica was most potent to induce IL - 6 regardless of how exposure was expressed, whereas the smallest size fraction of quartz was the most potent inducer of IL-8. Thus, the surface area seems to be the critical determinant when potency of different sizes of quartz is compared.

Wear of teeth due to occupational exposure to airborne olivine dust.

OBJECTIVES: To clarify whether high tooth wear of employees in a mining industry that extracts the mineral olivine could be associated with airborne dust exposure in their working environment. METHOD: The cumulative exposure to airborne mineral dust for the workers in the company was calculated on the basis of their period of employment multiplied by the airborne olivine-dust concentrations, which have been monitored continuously during the past 20 years for all divisions of the company. After invitation, 85% of the employees (n = 191) were examined clinically and their dentitions were photographed and duplicated in plaster casts. Four clinicians, working independently, examined the sets of casts/photographs for tooth wear and ranked these from most to least. Two groups of employees were compared with regard to tooth wear, i.e. the 30% with the highest (case) and the lowest (control) estimated dust exposure levels. Tooth wear in the case and control groups was compared using a non-parametric test based on rankings (Mann-Whitney test). RESULTS: Tooth wear differed significantly between the workers in the low and the high mineral dust exposure groups (p < 0.001). The differences were also apparent within three age subsets, although statistical significance was reached only in the 34-44 years subset (p = 0.002). Considerable individual variation was noted within the three exposure groups. CONCLUSION: Workers with high exposure to airborne olivine dust may contract considerable tooth wear.

Mineral particles of varying composition induce differential chemokine release from epithelial lung cells: importance of physico-chemical characteristics.

Presently, little is known about the potential health effects of mineral particles other than asbestos and quartz. In this study, a human epithelial lung cell line (A549), primary human small airway epithelial cells (SAECs) and primary rat type 2 (T2) cells were exposed to stone quarry particles of two size fractions (<10 and <2.5 microm) from nine different rock samples. The ability to induce the release of chemokines from lung cells was investigated and compared with the particles' mineral and element composition and the amount of soluble elements. The stone particles induced the release of only low levels of interleukin (IL)-8 from A549 cells. In contrast, some of the other particles induced the release of high levels of macrophage inflammatory protein (MIP)-2 from T2 cells, and high levels of IL-8 from SAECs. Differences in particle surface area could account for differences in activity between the <10 and <2.5 microm fractions of six out of the nine rock samples. For two samples the <2.5 microm fraction was most active and for one sample the <10 microm fraction was most active. Content of the mineral plagioclase displayed a strong, negative correlation with the potential to induce MIP-2, whereas the mineral pyroxene was positively correlated with MIP-2 induction. However, neither plagioclase nor pyroxene content was sufficient to explain differences in bioactivity between the particles. No statistically significant correlation was found between the amounts of total or soluble elements and MIP-2 release. In conclusion, the results suggest that mineral particles with a high content of plagioclase have a low potential to induce a pro-inflammatory response. However, a particular mineral or element responsible for eliciting strong increases in chemokine release could not be identified. Thus, at present it appears that analysing mineral and element content is insufficient to predict stone particle bioactivity, and that biological testing is a necessity.