Silica binding and toxicity in alveolar macrophages

Abstract

Inhalation of the crystalline form of silica is associated with a variety of pathologies from acute lung inflammation to silicosis, in addition to autoimmune disorders and cancer. Basic science researchers looking at the mechanisms involved with the earliest initiators of disease are focused on how the alveolar macrophage (AM) interacts with the inhaled silica particle and the consequences of silicainduced toxicity on the cellular level. Based on experimental results, several rationales have been developed on exactly how crystalline silica particles are toxic to the macrophage cell that is functionally responsible for clearance of the foreign particle. For example, silica is capable of producing reactive oxygen species (ROS) either directly (on the particle surface) or indirectly (produced by the cell as a response to silica) triggering cell-signaling pathways initiating cytokine release and apoptosis. With murine macrophages, reactive nitrogen species (RNS) are produced in the initial respiratory burst in addition to ROS. An alternative explanation for silica toxicity includes lysosomal permeability, where silica disrupts the normal internalization process leading to cytokine release and cell death. Still other research has focused on the cell surface receptors (collectively known as scavenger receptors) involved in silica binding and internalization. The silica-induced cytokine release and apoptosis is described as the function of receptor-mediated signaling rather than free radical damage. Current research ideas on silica toxicity and binding in the alveolar macrophage are reviewed and discussed.

Cytotoxicity and DNA Damage Induced by Magnetic Nanoparticle Silica in L5178Y Cell

“…As confocal microscope fi ndings showed that MNP@SiO 2 could enter the cell after treatment, irrespective of size, it may be owing to early cellular entry of MNP@SiO 2 . Base on recent reports that toxicity of silica nanoparticles was mediated through oxidant generation (Akhtar et al, 2010), and treatment of silica nanoparticles induced infl ammation (Hamilton et al, 2008) and enhanced infl ammatory cytokines (Nishimori et al, 2009), they could induce cellular toxicity even in larger size as well as small size.…”

Dispersion medium modulates oxidative stress response of human lung epithelial cells upon exposure to carbon nanomaterial samples

“…DPPC, the major component of lung surfactant, dispersed in physiological saline, has been used as simple model of lung surfactant in particle toxicity studies [Foucaud et al, 2007;Porter et al, 2008;Sager et al, 2007;Wallace et al, 1992;Wallace et al, 2007b]. In the case of silica toxicity, DPPC has been used as protective agent, inhibiting toxicity by particle coating [Hamilton et al, 2008;Patzold et al, 1993;Schimmelpfeng et al, 1992;Wallace et al, 1992]. However, it did not have a protective effect on chrysotile asbestos toxicity [Schimmelpfeng et al, 1992].…”

“…In addition, DPPC can affect particle toxicity by altering their surface chemistry and ultimately changing their toxicity [Buford et al, 2007;Hamilton et al, 2008;Wallace et al, 2007a;Wallace et al, 2007b]. Any potential contribution to the observed effects can be established by investigations which are currently underway.…”

The Nalp3 inflammasome is essential for the development of silicosis

“…It has been shown that treatment of macrophages with silica is cytotoxic (19). To determine whether silica-induced cytotoxicity was associated with Nalp3, we assessed the degree of cell death in WT and Nalp3-deficient macrophages after silica treatment.…”