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 language | English (US) |
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Pages (from-to) | 282-286 |
Number of pages | 5 |
Journal | Journal of Leukocyte Biology |
Volume | 57 |
Issue number | 2 |
DOIs | |
State | Published - 1995 |
Externally published | Yes |
Keywords
- Degranulation
- Difluoromethylornithine
- Inflammation
- Neutrophil
- Ornithine decarboxylase
- Respiratory burst
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Cell Biology