An inhibitor of polyamine biosynthesis impairs human polymorphonuclear leukocyte priming by tumor necrosis factor α

J. D. Walters, A. C. Cario, B. Leblebicioglu, M. C. Fernandez, Phillip Marucha

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

TNF primes polymorphonuclear leukocytes (PMNs) for enhanced oxidative and secretory activity and directly induces adhesion and IL-1β expression. Previous reports suggest that polyamine biosynthesis by ornithine decarboxylase (ODC) has an essential role in macrophage activation by TNF. In the current study, TNF induced rapid increases in the putrescine and spermine content of PMNs. Difluoromethylornithine (DFMO), a selective inhibitor of ODC, inhibited these increases and blunted the enhancement of superoxide generation and secondary granule release associated with priming by TNF. DFMO did not affect the expression of TNF receptors or block receptor-independent activation of the respiratory burst by phorbol esters. Moreover, DFMO did not antagonize induction of adhesion or IL-1β mRNA expression by TNF. Thus, polyamine biosynthesis plays an important role in priming by TNF, but is not involved in all PMN responses to this cytokine. This suggests that ODC is a potential target for selective chemotherapeutic modulation of the inflammatory response.

Original languageEnglish (US)
Pages (from-to)282-286
Number of pages5
JournalJournal of Leukocyte Biology
Volume57
Issue number2
StatePublished - 1995
Externally publishedYes

Fingerprint

Eflornithine
Polyamines
Neutrophils
Ornithine Decarboxylase
Tumor Necrosis Factor-alpha
Interleukin-1
Putrescine
Spermine
Respiratory Burst
Macrophage Activation
Tumor Necrosis Factor Receptors
Phorbol Esters
Superoxides
Cytokines
Messenger RNA

Keywords

  • Degranulation
  • Difluoromethylornithine
  • Inflammation
  • Neutrophil
  • Ornithine decarboxylase
  • Respiratory burst

ASJC Scopus subject areas

  • Cell Biology

Cite this

An inhibitor of polyamine biosynthesis impairs human polymorphonuclear leukocyte priming by tumor necrosis factor α. / Walters, J. D.; Cario, A. C.; Leblebicioglu, B.; Fernandez, M. C.; Marucha, Phillip.

In: Journal of Leukocyte Biology, Vol. 57, No. 2, 1995, p. 282-286.

Research output: Contribution to journalArticle

Walters, J. D. ; Cario, A. C. ; Leblebicioglu, B. ; Fernandez, M. C. ; Marucha, Phillip. / An inhibitor of polyamine biosynthesis impairs human polymorphonuclear leukocyte priming by tumor necrosis factor α. In: Journal of Leukocyte Biology. 1995 ; Vol. 57, No. 2. pp. 282-286.
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