PMID- 9368191
OWN - NLM
STAT- MEDLINE
DCOM- 19971219
LR  - 20141120
IS  - 1078-7852 (Print)
IS  - 1078-7852 (Linking)
VI  - 48
IP  - 1
DP  - 1998
TI  - An inhibitor of ornithine decarboxylase antagonizes superoxide generation by 
      primed human polymorphonuclear leukocytes.
PG  - 40-6
AB  - Tumor necrosis factor-alpha (TNF-alpha) 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 
      alpha-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-1 beta (IL-1 beta) 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 > or = 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.
FAU - Walters, J D
AU  - Walters JD
AD  - Section of Periodontology, College of Dentistry, Ohio State University Health 
      Sciences Center, Columbus 43210, USA. jwalters@postbox.acs.ohio-state.edu
FAU - Cario, A C
AU  - Cario AC
FAU - Danne, M M
AU  - Danne MM
FAU - Marucha, P T
AU  - Marucha PT
LA  - eng
GR  - K04 DE00338/DE/NIDCR NIH HHS/United States
GR  - R01 DE09851/DE/NIDCR NIH HHS/United States
GR  - R01 DE11014/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Inflamm
JT  - Journal of inflammation
JID - 9511967
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Ornithine Decarboxylase Inhibitors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11062-77-4 (Superoxides)
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - SY7Q814VUP (Calcium)
RN  - ZQN1G5V6SR (Eflornithine)
SB  - IM
MH  - Calcium/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Eflornithine/administration & dosage/*pharmacology
MH  - Enzyme Inhibitors/*pharmacology
MH  - Granulocyte Colony-Stimulating Factor/pharmacology
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology
MH  - Humans
MH  - Lipopolysaccharides/pharmacology
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/*drug effects/*metabolism
MH  - *Ornithine Decarboxylase Inhibitors
MH  - Respiratory Burst/drug effects
MH  - Superoxides/*blood
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 1997/11/22 00:00
MHDA- 1997/11/22 00:01
CRDT- 1997/11/22 00:00
PHST- 1997/11/22 00:00 [pubmed]
PHST- 1997/11/22 00:01 [medline]
PHST- 1997/11/22 00:00 [entrez]
PST - ppublish
SO  - J Inflamm. 1998;48(1):40-6.