Background Occupational exposure to crystalline silica is a well-established occupational hazard.
Background Occupational exposure to crystalline silica is a well-established occupational hazard. particles with a geometric mean of 0.3?m enhance the activation of AM when compared to larger silica particles usually represented in in vitro and in vivo research. Keywords: Ultrafine crystalline silica, Alveolar macrophage activation, Size segregation, Occupational aerosols Background Occupational exposure to crystalline silica (CS) 336113-53-2 affects at least 1.7 million US workers  and is associated with the development of silicosis, a fibrotic lung disease which is one of the most important occupational diseases worldwide [2C4]. The National Institute for Occupational Security and Health (NIOSH) reported that 300 silicosis-related deaths occurred each year in the United States between 1991 and 1995 . During those same years China recorded 24,000 silicosis-related deaths per year . These figures show that silicosis remains a fundamental occupational exposure problem in both the developing and developed countries . Exposure to CS occurs in many occupations and industries. The United States Occupational Safety and Health Administration (OSHA) measured detectable levels of respirable CS in samples collected in 255 different industries . In general, silica exposure will occur in any occupation that includes grinding or mechanically breaking material made up of silica (mining, construction) or handling fine particles containing silica, such as silica sand (fracking) [4, 8C12]. Although occupational exposure to CS and the related health effects have been well documented in the scientific literature, many uncertainties still exist including the effect of the crystals surface characteristics, including particle size, around the development of disease [8, 13C18]. Most atmospheric studies suggest that the concentration of smaller particles correlates better with adverse health effects 336113-53-2 than the concentration of larger particles [16, 19C22]; however, there is little size-dependent toxicity data concerning CS. One difficulty in completing size-dependent toxicity studies with CS is the difficulty in separating the occupational aerosol into distinct size ranges and in necessary quantities for toxicological studies. Recently our group published research on a novel multi-cyclone sampling array which enables the separation of occupational aerosols into distinct size ranges and in quantities needed for toxicological research . Because smaller particles have a higher surface area per unit mass when compared to larger particles, smaller particles may more readily initiate potential unfavorable biological reactions, such as inflammation . Chronic inflammation has been implicated in the pathogenesis of silicosis. In this scenario, the immune cells (alveolar macrophages, epithelial cells, and fibroblasts) are activated and release a host of inflammatory cytokines and generate reactive oxygen species (ROS), resulting in the recruitment of additional inflammatory cells, predominantly alveolar macrophages. The influx of additional inflammatory cells and release of ROS damages pulmonary architecture, causing accumulation of connective tissue products [7, 14, 25C27]. Knowledge of the degree to which particle size affects the activation of macrophages and the resulting ROS generation and inflammatory response is necessary for fully elucidating the mechanisms leading to silicosis from occupational exposure to crystalline silica. In the present in vitro study, the macrophage response to different-sized crystalline silica particles was evaluated in a well-established murine model [28, 29] using the mouse monocyte-macrophage RAW 264.7 cell line. Airborne CS particles were separated into four distinct size ranges using 336113-53-2 the multi-cyclone sampling array. The RAW 264.7 macrophages (AM) were exposed to four different sizes of 336113-53-2 CS and their activation was measured using electron Rabbit Polyclonal to NOC3L microscopy, mitochondrial ROS (mROS) generation, and cytokine expression. Methods Particles used for method evaluation The crystalline silica (SiO2 quartz, 99.9%, 1?m, Stock #: 4807YL) used in this study was purchased from Nanostructured & Amorphous Materials, Inc. (Houston, TX). Before particles were used in the experiment they were baked at 220?C for 24?h to destroy potential contaminating endotoxins. Particle separation The CS.