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)- in a mouse macrophage cell line (RAW 264.7). The underlying molecular mechanisms controlling TNF- production were investigated at the gene transcription level. The results show that glass fibers induced TNF- production in macrophages and that this induction was associated with activation of the gene promoter. Activation of the transcription factor nuclear factor (NF)-B was responsible for this induced promoter activity. The inhibition of both TNF- production and NF-B 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-B activation, the gene promoter activity, and the production of TNF-. 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.

nuclear factor-B; free radicals; tumor necrosis factor-

This article has been cited by other articles:

				C. Xie, A. Reusse, J. Dai, K. Zay, J. Harnett, and A. Churg TNF-alpha increases tracheal epithelial asbestos and fiberglass binding via a NF-kappa B-dependent mechanism Am J Physiol Lung Cell Mol Physiol, September 1, 2000; 279(3): L608 - L614. [Abstract] [Full Text] [PDF]

				J. Ye, P. Zeidler, S.-h. Young, A. Martinez, V. A Robinson, W. Jones, P. Baron, X. Shi, and V. Castranova Activation of Mitogen-activated Protein Kinase p38 and Extracellular Signal-regulated Kinase Is Involved in Glass Fiber-induced Tumor Necrosis Factor-alpha Production in Macrophages J. Biol. Chem., February 9, 2001; 276(7): 5360 - 5367. [Abstract] [Full Text] [PDF]

				Q. Ma and K. Kinneer Chemoprotection by Phenolic Antioxidants. INHIBITION OF TUMOR NECROSIS FACTOR alpha INDUCTION IN MACROPHAGES J. Biol. Chem., January 18, 2002; 277(4): 2477 - 2484. [Abstract] [Full Text] [PDF]