Activation of EGF receptors mediates pulmonary vasoconstriction induced by residual oil fly ash.

Published

Journal Article

Residual oil fly ash (ROFA) is a constituent of pollutant particles that can produce lung injury and activate protein tyrosine phosphorylation cascade. In this study, we determined whether or not protein tyrosine phosphorylation caused lung injury, and if so, identified critical tyrosinephosphorylated proteins that mediated the injury. ROFA was instilled intratracheally into perfused rabbit lungs and injury responses, including increase in pulmonary artery pressure (Ppa), lung weight gain, as well as release of interleukin (IL)-1beta, IL-6, IL-8, and nitrite/nitrate were measured. ROFA increased Ppa and IL-1beta, but inhibited nitrite/nitrate accumulation. Vanadyl sulfate at concentration equivalent to the amount of vanadium detected in the perfusate of ROFA-treated lungs induced similar changes. ROFA enhanced tyrosine phosphorylation of lung proteins, including a 170-kDa protein, likely the epidermal growth factor (EGF) receptor as shown by immunoprecipitation. Pretreatment with genistein, a tyrosine kinase inhibitor, blocked the increase in Ppa and tyrosine phosphorylation of the 170-kDa protein. Intravascular administration of human EGF increased Ppa, and pretreatment with PD153035, an EGF receptor-specific tyrosine kinase inhibitor, attenuated ROFA-induced pulmonary vasoconstriction. These results indicate that tyrosine phosphorylation of EGF receptors in the lung, possibly as a result of inhibition of protein tyrosine phosphatases, mediates constriction of pulmonary vessels induced by ROFA.

Full Text

Duke Authors

Cited Authors

  • Huang, Y-CT; Wu, W; Ghio, AJ; Carter, JD; Silbajoris, R; Devlin, RB; Samet, JM

Published Date

  • January 2002

Published In

Volume / Issue

  • 28 / 1

Start / End Page

  • 19 - 38

PubMed ID

  • 11792073

Pubmed Central ID

  • 11792073

Electronic International Standard Serial Number (EISSN)

  • 1521-0499

International Standard Serial Number (ISSN)

  • 0190-2148

Digital Object Identifier (DOI)

  • 10.1080/019021402753355517

Language

  • eng