Ambient but not incremental oxidant generation effects intercellular adhesion molecule 1 induction by tumour necrosis factor alpha in endothelium.


Journal Article

Proinflammatory cytokines upregulate endothelial adhesion molecule expression, thereby initiating the microvascular inflammatory response. We re-evaluated the reported role of reactive oxygen metabolites (ROMs) in signalling upregulation of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells by tumour necrosis factor alpha (TNF-alpha) in vitro. TNF-alpha upregulation of endothelial-cell ICAM-1 expression was inhibited by the cell-permeable antioxidants, or by the adenovirus-mediated intracellular overexpression of Cu,Zn-superoxide dismutase, but not by the exogenous (extracellular) administration of the cell-impermeable antioxidants, superoxide dismutase and/or catalase. This ICAM-1 upregulation was also inhibited by inhibitors of NADH dehydrogenase, cytochrome bc1 complex and NADPH oxidase. However, a measurable increase in net cellular ROM generation in response to TNF-alpha was not seen using four disparate sensitive ROM assays. Moreover, the stimulation of exogenous or endogenous ROM generation did not upregulate ICAM-1, nor enhance ICAM-1 upregulation by TNF-alpha. These findings suggest that an ambient background flux of ROMs, generated intracellularly, but not their net incremental generation, is necessary for TNF-alpha to induce ICAM-1 expression in endothelium in vitro.

Full Text

Cited Authors

  • Arai, T; Kelly, SA; Brengman, ML; Takano, M; Smith, EH; Goldschmidt-Clermont, PJ; Bulkley, GB

Published Date

  • May 1998

Published In

Volume / Issue

  • 331 ( Pt 3) /

Start / End Page

  • 853 - 861

PubMed ID

  • 9560314

Pubmed Central ID

  • 9560314

Electronic International Standard Serial Number (EISSN)

  • 1470-8728

International Standard Serial Number (ISSN)

  • 0264-6021

Digital Object Identifier (DOI)

  • 10.1042/bj3310853


  • eng