An inhibitor of ornithine decarboxylase antagonizes superoxide generation by primed human polymorphonuclear leukocytes

John D. Walters, A. C. Cario, M. M. Danne, P. T. Marucha

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Tumor necrosis factor-α (TNF-α) induces a rapid increase in polymorphonuclear leukocyte (PMN) polyamine content which appears to be required for optimal priming of the respiratory burst. The objective of the present study was to determine whether inhibition of polyamine biosynthesis modifies PMN responses to lipopolysaccharide (LPS), granulocyte-macrophage colony-stimulating factor (GM-CSF), or granulocyte colony-stimulating factor (G-CSF). Treatment with α-difluoromethylornithine (DFMO), a selective inhibitor of the rate-limiting biosynthetic enzyme ornithine decarboxylase, produced dose-dependent inhibition of the respiratory burst in PMNs that were primed by these agents and subsequently activated by formyl-Met-Leu-Phe (fMLP). However, DFMO did not significantly inhibit fMLP-stimulated superoxide generation or alter the induction of PMN adhesion and interleukin- 1β (IL-1β) mRNA expression by LPS or GM-CSF. Antagonism of priming by DFMO correlated with a dose-dependent attenuation of fMLP-induced intracellular Ca2+ mobilization (r ≤ 0.96). Since Ca2+ plays an important role in modulating the respiratory burst in primed PMNs, this could, in part, account for the selective effects of DFMO.

Original languageEnglish (US)
Pages (from-to)40-46
Number of pages7
JournalJournal of Inflammation
Volume48
Issue number1
StatePublished - 1998

Keywords

  • Ca signaling
  • Difluoromethylornithine
  • G-CSF
  • GM-CSF
  • Inflammation
  • Lipopolysaccharide
  • Neutrophil
  • Polyamines
  • Respiratory burst
  • TNF-α

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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