Differential activation of RAW 264.7 macrophages by size-segregated crystalline silica
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RESEARCH
Open Access
Differential activation of RAW 264.7 macrophages by size-segregated crystalline silica Steven E. Mischler1*, Emanuele G. Cauda1, Michelangelo Di Giuseppe2, Linda J. McWilliams1, Claudette St. Croix3, Ming Sun4, Jonathan Franks4 and Luis A. Ortiz2
Abstract Background: Occupational exposure to crystalline silica is a well-established occupational hazard. Once in the lung, crystalline silica particles can result in the activation of alveolar macrophages (AM), potentially leading to silicosis, a fibrotic lung disease. Because the activation of alveolar macrophages is the beginning step in a complicated inflammatory cascade, it is necessary to define the particle characteristics resulting in this activation. The aim of this research was to determine the effect of the size of crystalline silica particles on the activation of macrophages. Methods: RAW 264.7 macrophages were exposed to four different sizes of crystalline silica and their activation was measured using electron microscopy, reactive oxygen species (ROS) generation by mitochondria, and cytokine expression. Results: These data identified differences in particle uptake and formation of subcellular organelles based on particle size. In addition, these data show that the smallest particles, with a geometric mean of 0.3 μm, significantly increase the generation of mitochondrial ROS and the expression of cytokines when compared to larger crystalline silica particles, with a geometric mean of 4.1 μm. Conclusion: In summary, this study presents novel data showing that crystalline silica particles with a geometric mean of 0.3 μm 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) affects at least 1.7 million US workers [1] and is associated with the development of silicosis, a fibrotic lung disease which is one of the most important occupational diseases worldwide [2–4]. The National Institute for Occupational Safety and Health (NIOSH) reported that 300 silicosis-related deaths occurred each year in the United States between 1991 and 1995 [5]. During those same years China recorded 24,000 silicosis-related deaths per year [6]. These numbers indicate that silicosis remains a
* Correspondence: [email protected] 1 National Institute for Occupational Safety and Health, Office of Mine Safety and Health Research, 626 Cochrans Mill Road, Pittsburgh, PA 15236, USA Full list of author information is available at the end of the article
fundamental occupational exposure problem in both the developing and developed countries [7]. 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 [1]. In general, silica exposure will occur in any occupation that i
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