Nanoscience and nanotechnology: environmental and health impacts. Grassian VH ed., Hoboken, NJ: John Wiley & Sons, 2008 Oct; :287-318
In this chapter, we have summarized results of our studies that suggest a contributing role for surface Fenton-reactive metal ion in particulate-mediated inflammatory activation of macrophages and the consequent endothelial inflammatory activation by macrophage-elaborated soluble factors. Specifically. we have demonstrated that pure carbon particulates show little or no Fenton reactivity with H202 as indicated by ESR of DMPO- OH adducts, and induce little if any TNF-a production by exposed macrophages. In contrast. equivalent doses of carbon-iron (C-Fe) particulates generate strong ESR DMPO-OH signals following reaction with H202 and induce high levels of TNF-a production by exposed macrophages in a dose-dependent manner. Furthermore, clarified culture supernatants recovered from C- Fe-treated macrophages raise vascular endothelial cells to an activated state as indicated by the induction of endothelial- leukocyte adhesion molecules ICAM-1, VCAM-1, and E-selectin. Finally, our observation that 100 nm particulates elicit much stronger responses than an equivalent mass of their 1-um counterparts argues in favor of a role for surface chemistry in particulate-induced inflammation. Various types of particulates have been demonstrated to induce the expression of a number of additional proinflammatory cytokines, chemokines, and receptors in exposed cultured cells, including interleukin (IL)-1B, IL-6, macrophage inflammatory protein-2 (MIP-2), histamine HI receptor (HIR), IL-8, granulocyte macrophagecolony stimulating factor (GM-CSF), and monocyte chemoattractant protein-1 (MCP- 1), effects which in some cases can be inhibited by antioxidants. Macrophages exposed to high concentrations (200 ug/mL) of ultrafine carbon black (14 nm) have been shown to produce a modest level ofTNF-a, which can be blocked by introduction of the calcium channel blocker verapimil. It has been proposed that production of ROS leads to the oxidation of calcium pumps in the endoplasmic reticulum. The role of free radicals and reactive oxygen species created upon ultrafine particle inhalation in causing inflammation is being recognized for different types of particulates. Iron can lead to the formation of hydroxyl radicals through the Fenton mechanism. Iron-containing particles have been proposed as a mechanism of introducing unregulated iron into cells, and soluble iron has been shown to induce the expression ofTNF-a in Kupffer cells, which was preceded by an increase in hydroxyl radicals. Collectively, these findings suggest oxidative stress, induced by particulates in alveolar macrophages and possibly alveolar epithelia, as a potential contributing factor in the pathogenesis of pulmonary disease or exacerbation of existing disease associated with exposure to airborne particulates. Oxidative stress, in turn, triggers an inflammatory response in macrophages, which act as both phagocytes and sentinels in the lung and other tissues, resulting in their elaboration of TNF-a and other proinflammatory cytokines and chemokines. TNF-a then induces the expression of leukocyte adhesion molecules upon proximal septal capillary endothelium resulting in the recruitment of inflammatory leukocytes to the site. While in the case of acute injury or infection, inflammation is a beneficial response, required to clear pathogens or toxins and to initiate wound healing. chronic nonresolving inflammation, as would be expected under conditions of protracted inhalation exposure to airborne particulates. can lead to pennanent tissue remodeling and fibrosis , as has been observed in individuals following long-term exposure. Carbon-based nanomaterials including carbon nanoparticles are being considered for many applications, including optical devices, electronic applications, and biomedical use, for example, drug delivery. However, potential hazards stemming from exposure to carbon particulates are still being debated. In the context of the studies described here, as particles decrease in size with manifestation of novel properties. both the increased surface area and the functionality on the surface will play important roles in their biological activity.
Nanotechnology; Epidemiology; Biological-factors; Biological-material; Biological-effects; Mineral-dusts; Minerals; Fiber-deposition; Fibrous-dusts; Particulates; Particulate-dust; Metal-compounds; Metal-dusts; Metallic-ions; Toxins; Toxic-materials; Toxic-effects; Surface-properties; Chemical-composition; Chemical-properties; Chemical-reactions; Cell-damage; Cell-function; Cellular-reactions; Cell-biology; Exposure-levels; Lung-disease; Respiratory-system-disorders; Pulmonary-system-disorders; Pulmonary-system; Pulmonary-function; Pulmonary-disorders