Disruption of protein tyrosine phosphate homeostasis in bronchial epithelial cells exposed to oil fly ash. Samet, James M., Jackie Stonehuerner, William Reed, Robert B. Devlin, Lisa A. Dailey, Thomas P. Kennedy, Philip A. Bromberg, and Andrew J. Ghio. Center for Environmental Medicine and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, and Human Studies Division, U.S. Environmental Protection Agency, Research Triangle Park, NC
APStracts 3:0192L, 1996.
Residual oil fly ash (ROFA) is a toxic air pollutant which we have previously shown induces inflammatory mediator expression in human bronchial epithelial cells. To identify intracellular signaling mechanisms activated by ROFA, we studied its effect on protein tyrosine phosphate metabolism in the human bronchial epithelial cell line BEAS. Non-cytotoxic levels of ROFA induced significant dose- and time-dependent increases in protein tyrosine phosphate levels in BEAS cells. ROFA-induced increases in protein phosphotyrosines was associated with its soluble fraction and was mimicked by vanadyl- (V(IV)) and vanadate (V(V))-containing solutions. Ferrous, ferric and nickel (II) ion solutions failed to increase phosphotyrosine levels. Tyrosine phosphatase activity, known to be inhibited by vanadium ions, was markedly diminished after ROFA treatment. Tyrosine kinase activity was unaffected. We conclude that ROFA exposure induces vanadium-ion mediated inhibition of tyrosine phosphatase activity, leading to accumulation of protein phosphotyrosines in BEAS cells. These findings demonstrate that ROFA exposure disrupts protein tyrosine phosphate homeostasis in BEAS cells and suggest a possible mechanism that leads to increased synthesis of pro-inflammatory proteins in airway epithelial cells exposed to PM10.

Received 30 July 1996; accepted in final form 9 October 1996.
APS Manuscript Number L242-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996