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

Recent studies have demonstrated that dielectrophoresis is an efficient met hod for the separation of fibers according to fiber length. This method all ows the investigation of fiber-cell interactions with fiber samples of the same composition but of different lengths. In the present study, we analyze d the effects of length on the interaction between glass fibers and macroph ages by focusing on production of the inflammatory cytokine tumor necrosis factor (TNF)-alpha in a mouse macrophage cell line (RAW 264.7). The underly ing molecular mechanisms controlling TNF-alpha production were investigated at the gene transcription level. The results show that glass fibers induce d TNF-alpha production in macrophages and that this induction was associate d with activation of the gene promoter. Activation of the transcription fac tor nuclear factor (NF)-kappa B was responsible for this induced promoter a ctivity. The inhibition of both TNF-alpha production and NF-kappa B activat ion by N-acetyl-L-cysteine, an antioxidant. indicates that generation of ox idants mag contribute to the induction of this cytokine and activation of t his transcription factor by glass fibers. Long fibers (17 mu m) were signif icantly more potent than short fibers (7 mu m) in inducing NF-kappa B activ ation, the gene promoter activity, and the production of TNF-alpha. This fi ber 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 s uggest that fiber length plays a critical role in the potential pathogenici ty of glass fibers.