TNF-alpha increases tracheal epithelial asbestos and fiberglass binding via a NF-kappa B-dependent mechanism

Tumor necrosis factor (TNF)-alpha is released from alveolar macrophages aft er phagocytosis of mineral fibers. To determine whether TNF-alpha affects t he binding of fibers to epithelial cells, we exposed rat tracheal explants to TNF-alpha or to culture medium alone, followed by a suspension of amosit e asbestos or fiberglass (MMVF10). Loosely adherent fibers were removed fro m the surface with a standardized washing technique, and the number of boun d fibers was determined by scanning electron microscopy. Increasing doses o f TNF-alpha produced increases in fiber binding. This effect was abolished by an anti-TNF-alpha antibody, the proteasome inhibitor MG-132, and the nuc lear factor (NF)-kappa B inhibitor pyrrolidine dithiocarbamate. Gel shift a nd Western blot analyses confirmed that TNF-alpha activated NF-kappa B and depleted I kappa B in this system and that these effects were prevented by MG-132 and pyrrolidine dithiocarbamate. These observations indicate that TN F-alpha increases epithelial fiber binding by a NF-kappa B-dependent mechan ism. They also suggest that mineral particles may cause pathological lesion s via an autocrine-like process in which the response evoked by particles, for example, macrophage TNF-alpha production, acts to enhance subsequent in teractions of particles with tissue.