Tumor necrosis factor (TNF)- is released from alveolar macrophages after phagocytosis of mineral fibers. To determine whether TNF- affects the binding of fibers to epithelial cells, we exposed rat tracheal explants to TNF- or to culture medium alone, followed by a suspension of amosite asbestos or fiberglass (MMVF10). Loosely adherent fibers were removed from the surface with a standardized washing technique, and the number of bound fibers was determined by scanning electron microscopy. Increasing doses of TNF- produced increases in fiber binding. This effect was abolished by an anti-TNF- antibody, the proteasome inhibitor MG-132, and the nuclear factor (NF)-B inhibitor pyrrolidine dithiocarbamate. Gel shift and Western blot analyses confirmed that TNF- activated NF-B and depleted IB in this system and that these effects were prevented by MG-132 and pyrrolidine dithiocarbamate. These observations indicate that TNF- increases epithelial fiber binding by a NF-B-dependent mechanism. They also suggest that mineral particles may cause pathological lesions via an autocrine-like process in which the response evoked by particles, for example, macrophage TNF- production, acts to enhance subsequent interactions of particles with tissue.