Lung mucin production is stimulated by the air pollutant residual oil fly ash

Human and animal exposure to particulate air pollution is correlated with a irway mucus hypersecretion and increased susceptibility to infection. Seeki ng clues to the mechanisms underlying this pathology, we examined the effec t of the particulate air pollutant residual oil fly ash (ROFA) on productio n of the major component of mucus, mucin, and the major antibacterial prote in of the respiratory tract, lysozyme. We found that following in vitro exp osure to ROFA, epithelial cells showed an increase in mucin (MUC5AC) and ly sozyme (LYS) steady state mRNA. This upregulation was controlled at least p artly at the level of transcription as shown by reporter assays. Experiment s testing the ability of the major components of ROFA to mimic these effect s showed that vanadium, a metal making up 18.8% by weight, accounted for th e bulk of the response. A screen of signaling inhibitors showed that MUC5AC and LYS induction by ROFA are mediated by dissimilar signaling pathways, b oth of which are, however, phosphotyrosine dependent. Recognizing that the ROFA constituent vanadium is a potent tyrosine phosphatase inhibitor and th at mucin induction by pathogens is phophotyrosine dependent, we suggest tha t vanadium-containing air pollutants trigger disease-like conditions by unm asking phosphorylation-dependent pathogen resistance pathways. (C) 2000 Aca demic Press.