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