Rapid upregulation of endothelial P-selectin expression via reactive oxygen species generation

Manabu Takano, Avedis Meneshian, Emran Sheikh, Yasuhiko Yamakawa, Kirsten Bass Wilkins, Elise A. Hopkins, Gregory B. Bulkley

Research output: Contribution to journalArticlepeer-review

Abstract

Endothelial cell ICAM-1 upregulation in response to TNF-α is mediated in part by reactive oxygen species (ROS) generated by the endothelial membrane-associated NADPH oxidase and occurs maximally after 4 h as the synthesis of new protein is required. However, thrombin-stimulated P-selectin upregulation is bimodal, the first peak occurring within minutes. We hypothesize that this early peak, which results from the release of preformed P-selectin from within Weibel-Palade bodies, is mediated in part by ROS generated from the endothelial membrane-associated xanthine oxidase. We found that this rapid expression of P-selectin on the surface of endothelial cells was accompanied by qualitatively parallel increases in ROS generation. Both P-selectin expression and ROS generation were inhibited, dose dependently, by the exogenous administration of disparate cell-permeable antioxidants and also by the inhibition of either of the known membrane-associated ROS-generating enzymes NADPH oxidase or xanthine oxidase. This rapid, posttranslational cell signaling response, mediated by ROS generated not only by the classical NADPH oxidase but also by xanthine oxidase, may well represent an important physiological trigger of the microvascular inflammatory response.

Original languageEnglish (US)
Pages (from-to)H2054-H2061
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume283
Issue number5 52-5
DOIs
StatePublished - Nov 1 2002

Keywords

  • NADPH oxidase
  • Oxidant signaling
  • Signal transduction
  • Xanthine oxidase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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