Single-walled carbon nanotubes activate RAW 264.7 macrophages: role in oxidative stress and inflammatory response.
Potapovich-AI; Osipov-AN; Kisin-ER; Schwegler-Berry-D; Shvedova-AA; Kagan-VE
Toxicologist 2005 Mar; 84(Suppl 1):468
Single-walled carbon nanotubes (SWCNT) are an important member of nanomaterials with potentially broad range of revolutionary applications. Unprocessed SWCNT could become airborne and potentially reach lungs. Yet their pulmonary toxicity remains poorly characterized. The most commonly used technology in the manufacturing of SWCNT is catalytic disproportionation of gaseous CO on catalytic iron particles. Thus, SWCNT usually contain significant amounts (up to 40 wt%) of iron that may act as a catalyst of oxidative stress. Because inflammation induced by SWCNT provides a redox environment in which iron can fully realize their pro-oxidant potential, a combination of inflammatory response with catalytically-competent iron-containing SWCNT may synergistically enhance damage to cells and tissue. The primary responder that initiates inflammatory reaction to particle challenge is the pulmonary macrophages. Therefore, we used RAW 264.7 macrophages as a cell culture model to characterize the ability of these cells to respond to SWCNT with different levels of iron. Using EPR spectroscopy we found that non-purified in contrast to purified SWCNT displayed a broad signal attributable to high spin Fe3+ in a distorted tetrahedral environment. Co-incubation of macrophages with SWCNT resulted in their engulfment detectable by TEM. Depletion of GSH and an increased number of apoptotic cells in response to SWCNT was observed. No intracellular production of superoxide (O2) or NO was triggered by SWCNT as evidenced by flow cytometry. Iron-rich (but not irondeplete) SWCNT effectively catalyzed conversion of extracellularly generated O2 into hydroxyl radicals after zymosan activation of macrophages or in the presence of xanthine oxidase/xanthine as documented by EPR. Both iron-rich and iron-deplete SWCNT stimulated release of pro-inflammatory and fibrogenic cytokines IL-6 and TGF-B, respectively.
Toxins; Toxic-effects; Oxidative-processes; Stress; Cell-damage; Cell-cultures; Models; Iron-oxides; Pulmonary-system-disorders; Lung-disorders; Respiratory-system-disorders; Aerosol-particles; Aerosols; Particulate-dust; Particulates; Nanotechnology
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
The Toxicologist. Society of Toxicology 44th Annual Meeting and ToxExpo, March 6-10, 2005, New Orleans, Louisiana