The inhalation of airborne pollutants, such as asbestos or silica, is linked to inflammation of the lung, fibrosis, and lung cancer. How the presence of pathogenic dust is recognized and how chronic inflammatory diseases are triggered are poorly understood. Here, we show that asbestos and silica are sensed by the Nalp3 inflammasome, whose subsequent activation leads to interleukin 1β secretion. Inflammasome activation is triggered by reactive oxygen species, which are generated by a NADPH oxidase upon particle phagocytosis (NADPH is the reduced form of nicotinamide adenine dinucleotide phosphate). In a model of asbestos inhalation, Nalp3 −/− mice showed diminished recruitment of inflammatory cells to the lungs, paralleled by lower cytokine production. Our findings implicate the Nalp3 inflammasome in particulate matter-related pulmonary diseases and support its role as a major proinflammatory "danger" receptor.
Asbestos is a commercial term for a group of fibrous minerals often associated with the development of pulmonary interstitial fibrosis (asbestosis), lung cancer, and malignant mesothelioma in occupationally exposed individuals. The pathogenicity of different forms of asbestos varies--long, thin amphibole fibers are most pathogenic, particularly in the induction of mesothelioma. Available data do not support the concept that low-level exposure to asbestos is a health hazard in buildings and schools. The concentration of asbestos fibers in air, type of asbestos, and size of fibers must be considered in evaluation of potential health risks.
Asbestos is a ubiquitous, naturally occurring fiber that has been linked to the development of malignant and fibrotic diseases of the lung and pleura. These diseases may be initiated by injury to epithelial cells and mesothelial cells by asbestos fibers through the formation of reactive oxygen intermediates. Elaboration of oxidants are also a consequence of inflammation, a hallmark of exposure to asbestos after inhalation or injection of asbestos fibers into animals. The type, size, and durability of asbestos fibers may be important in toxicity and pathogenicity of asbestos types. This review discusses the pathways of oxidant generation by asbestos fibers, cell-cell interaction that may initiate and perpetuate inflammation, cytokine release and proliferative responses to asbestos, and cell signaling pathways implicated in these events.
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