Macrophage Culture as a Suitable Paradigm for Evaluation of Synthetic Vitreous Fibers

Abstract

The ultimate goal of toxicologic investigation of synthetic vitreous fibers (SVFs) is to provide essential input for the assessment of human risk to their exposure. Toxicity of mineral fibers is usually evaluated by testing biopersistence in rodent model. However, a cellular model would be much appreciated in order to reduce, refine, and replace animal models. Pulmonary disorders triggered by inhalation of occupational or environmental mineral particulates can be the endpoints of a chronic inflammatory process in which alveolar macrophages (AMs) play a crucial role. Depending on the type of SVF involved, phagocytosis of fiber leads to activation of macrophages, resulting in release of fiber components and potent mediators, such as reactive oxygen or nitrogen species and cytokines. As a matter of fact, macrophages should be the cells of choice since SVF toxicity is the consequence of fibers and alveolar macrophages interaction. Today, monocytes and macrophages culture are firmly established as a paradigm in toxicology when several endpoints are assayed in macrophages: (1) fiber durability, (2) fiber surface changes, (3) oxidative stress and genotoxicity in macrophage, and (4) macrophage cell viability and apoptosis. This article is a review of up-to-date knowledge of in vitro studies involving macrophages, and assesses endpoints of macrophage toxicity with an emphasis on (1) dissolution, (2) scanning electron microscopy analysis, (3) cytotoxicity, and (4) gene expression.

Carbon nanotubes induce oxidative DNA damage in RAW 264.7 cells

“…Among the wide range of cell models available for in vitro toxicology studies of NP, we chose the RAW 264.7 cells, because macrophages are critical components of the innate immune response against microbial pathogens or inhaled particulate matter [Nguea et al, 2008]. Moreover, the role of macrophage lineages in ROS generation and induction of other biochemical effects following CNT exposure has been extensively studied, whereas few studies have considered that the possible consequences at a Environmental and Molecular Mutagenesis.…”

Biodurability of single-walled carbon nanotubes depends on surface functionalization

“…Dissolution and/or degradation alters the biological distribution and fate of foreign materials in the body [17], and for mineral fibers this biodurability is commonly assessed by measuring dissolution rates in macrophage cultures [18] or in cell-free chemical assays [19]. …”

Biochemistry in Assessing the Inflammatory Response of the Respiratory System Due to Experimental Exposure to Glass Fibres

“…The biopersistence of glass fibers refers to their ability to persist in the lung and represents a critical factor in assessing the effects of fibers on lung, by taking their different properties into account: solubility and physiological clearance at tissue level. Such properties of glass fibers as dose, size, chemical composition, electrical charge are other determinants of the ability of alveolar macrophages to engulf and remove efficiently fibers from the lungs, or to persist in the lungs and cause a chronic inflammatory response [29]. The design of a subchronic toxicity study requires three fundamental elements: the preparation and characterization of the fibers to be tested, the assessment of biopersistence in vivo and the determination of toxicological effects at gastrointestinal level [11,27,[30][31][32].…”