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

John D. Walters, A. C. Cario, M. M. Danne, Phillip Marucha

Research output: Contribution to journalArticle

5 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Eflornithine
methionyl-leucyl-phenylalanine
Superoxides
Respiratory Burst
Neutrophils
Polyamines
Granulocyte-Macrophage Colony-Stimulating Factor
Lipopolysaccharides
Ornithine Decarboxylase
Granulocyte Colony-Stimulating Factor
Interleukin-1
Tumor Necrosis Factor-alpha
Messenger RNA
Ornithine Decarboxylase Inhibitors
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

An inhibitor of ornithine decarboxylase antagonizes superoxide generation by primed human polymorphonuclear leukocytes. / Walters, John D.; Cario, A. C.; Danne, M. M.; Marucha, Phillip.

In: Journal of Inflammation, Vol. 48, No. 1, 1998, p. 40-46.

Research output: Contribution to journalArticle

@article{b4386875f605492da676d8c5ea101669,
title = "An inhibitor of ornithine decarboxylase antagonizes superoxide generation by primed human polymorphonuclear leukocytes",
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.",
keywords = "Ca signaling, Difluoromethylornithine, G-CSF, GM-CSF, Inflammation, Lipopolysaccharide, Neutrophil, Polyamines, Respiratory burst, TNF-α",
author = "Walters, {John D.} and Cario, {A. C.} and Danne, {M. M.} and Phillip Marucha",
year = "1998",
language = "English (US)",
volume = "48",
pages = "40--46",
journal = "Journal of inflammation",
issn = "1078-7852",
publisher = "Springer Nature",
number = "1",

}

TY - JOUR

T1 - An inhibitor of ornithine decarboxylase antagonizes superoxide generation by primed human polymorphonuclear leukocytes

AU - Walters, John D.

AU - Cario, A. C.

AU - Danne, M. M.

AU - Marucha, Phillip

PY - 1998

Y1 - 1998

N2 - 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.

AB - 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.

KW - Ca signaling

KW - Difluoromethylornithine

KW - G-CSF

KW - GM-CSF

KW - Inflammation

KW - Lipopolysaccharide

KW - Neutrophil

KW - Polyamines

KW - Respiratory burst

KW - TNF-α

UR - http://www.scopus.com/inward/record.url?scp=0031986069&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031986069&partnerID=8YFLogxK

M3 - Article

VL - 48

SP - 40

EP - 46

JO - Journal of inflammation

JF - Journal of inflammation

SN - 1078-7852

IS - 1

ER -