Critical role of glass fiber length in TNF-α production and transcription factor activation in macrophages

Abstract

Recent studies have demonstrated that dielectrophoresis is an efficient method for the separation of fibers according to fiber length. This method allows the investigation of fiber-cell interactions with fiber samples of the same composition but of different lengths. In the present study, we analyzed the effects of length on the interaction between glass fibers and macrophages by focusing on production of the inflammatory cytokine tumor necrosis factor (TNF)-α in a mouse macrophage cell line (RAW 264.7). The underlying molecular mechanisms controlling TNF-α production were investigated at the gene transcription level. The results show that glass fibers induced TNF-α production in macrophages and that this induction was associated with activation of the gene promoter. Activation of the transcription factor nuclear factor (NF)-κB was responsible for this induced promoter activity. The inhibition of both TNF-α production and NF-κB activation by N-acetyl-l-cysteine, an antioxidant, indicates that generation of oxidants may contribute to the induction of this cytokine and activation of this transcription factor by glass fibers. Long fibers (17 μm) were significantly more potent than short fibers (7 μm) in inducing NF-κB activation, the gene promoter activity, and the production of TNF-α. This fiber length-dependent difference in the stimulatory potency correlated with the fact that macrophages were able to completely engulf short glass fibers, whereas phagocytosis of long glass fibers was incomplete. These results suggest that fiber length plays a critical role in the potential pathogenicity of glass fibers.

Length-Dependent Retention of Carbon Nanotubes in the Pleural Space of Mice Initiates Sustained Inflammation and Progressive Fibrosis on the Parietal Pleura

“…Length-dependent pathogenicity of asbestos and other fibers is one of the defining properties of the fiber pathogenicity paradigm 17 and has been documented in several models in vivo 9,22-25 and in vitro, [25][26][27] whereas frustrated or incomplete phagocytosis by macrophages has been implicated as a mechanism leading to inflammation with long fibers 26 and CNTs. 28 Length-related retention was first advanced by Kane et al 12 to explain length-dependent asbestos inflammation in the peritoneal cavity.…”

Measurement of Airborne Fibers: A Review.

“…597-611 Copyright (1992) with permission of Elsevier Science). assays 8,83) . It was also demonstrated that the dielectrophoresis classifier could be used to measure bivariate fiber distributions when combined with an aerodynamic sizing instrument such as the Aerosizer (TSI, Inc. Minneapolis) 84) .…”

Magnetometric Evaluation of the Effects of Man-Made Mineral Fibers on the Function of Macrophages Using the Macrophage Cell Line RAW 264.7

“…The number of AMs obtained from each rat is limited to several millions, therefore, many animals are needed to evaluate each substance. Recently the murine macrophage cell line RAW 264.7 became available and has been used as an in vitro model of AMs [14][15][16] . Cell magnetometry using RAW 264.7 cells may be useful.…”