kaolinite and Pneumonia

Manufactured nanomaterials are projected to be used on a large scale in paints and lacquers. We selected seven commercially interesting materials: Three titanium dioxide-based (two coated rutile; one uncoated anatase), one carbon black (Flamrüss 101), one kaolinite clay, and two silica products, whereas carbon black, Printex 90, was used as reference material. DNA damaging activity and inflammogenicity (pulmonary cell composition and mRNAs) were determined 24 h after intratracheal instillation of a single dose of 54 μg in mice. Greatest inflammation was induced by Printex 90 and uncoated titanium dioxide. The inflammatory potency correlated with instilled surface area (R(2) = 0.94) but not with material volume (R(2) = 0.17). The coated titanium dioxides induced DNA damage in lung lining fluid cells. The uncoated titanium dioxide was not DNA damaging by the comet assay 24 h after exposure despite being highly inflammogenic. This suggests that inflammation is not a prerequisite to DNA damage in titanium dioxide-based products.

Topics: Administration, Inhalation; Analysis of Variance; Animals; Cell Survival; DNA Damage; Female; Kaolin; Mice; Mice, Inbred C57BL; Nanoparticles; Oxidative Stress; Paint; Pneumonia; Reactive Oxygen Species; Silicon Dioxide; Soot; Titanium

The respiratory health impact of Asian sand dust events originating in the deserts of China has become a concern within China and in its neighboring countries. We examined the effects of Asian sand dust particles (ASDPs) on gene expression in the murine lung using microarray analysis and elucidated the components responsible for lung inflammation. Male ICR mice were intratracheally administrated ASDPs, heat-treated ASDPs (ASDP-F, lipopolysaccaride [LPS], or beta-glucan free), or kaolin particles. We performed microarray analysis for murine lungs, the results of which were confirmed by quantitative reverse transcription-polymerase chain reaction (RT-PCR). We also assessed the protein expression and histologic changes. Exposure to ASDP, ASDP-F, or kaolin upregulated (>2-fold) 112, 36, or 9 genes, respectively, compared with vehicle exposure. In particular, ASDP exposure markedly enhanced inflammatory response-related genes, including chemokine (C-X-C motif) ligand 1/keratinocyte-derived chemokine, chemokine (C-X-C motif) ligand 2/macrophage inflammatory protein-2, chemokine (C-C motif) ligand 3/macrophage inflammatory protein-1alpha, and chemokine (C-X-C motif) ligand 10/interferon-gamma-inducible protein-10 (>6-fold). The results were correlated with those of the quantitative RT-PCR and the protein expression analyses in overall trend. In contrast, exposure to ASDP-F attenuated the enhanced expression of these proinflammatory molecules. Kaolin exposure increased the expression of genes and proteins for the chemokines. In histopathologic changes, exposure to ASDP prominently enhanced pulmonary neutrophilic inflammation, followed by kaolin and ASDP-F exposure in the order. Taken together, exposure to ASDP causes pulmonary inflammation via the expression of proinflammatory molecules, which can be attributed to LPS and beta-glucan absorbed in ASDPs. Furthermore, microarray analysis should be effective for identifying potentially novel genes, sensitive biomarkers, and pathways involved in the health effects of the exposure to environmental particles (e.g., ASDPs).

Topics: Animals; Chemokines; China; Desert Climate; Dust; Gene Expression Profiling; Gene Expression Regulation; Humans; Inflammation Mediators; Inhalation Exposure; Kaolin; Lipopolysaccharides; Lung; Male; Mice; Mice, Inbred ICR; Oligonucleotide Array Sequence Analysis; Pneumonia; Silicon Dioxide