PMID- 8196365
OWN - NLM
STAT- MEDLINE
DCOM- 19940627
LR  - 20131121
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 70
IP  - 5
DP  - 1994 May
TI  - Priming for the synthesis of 5-lipoxygenase products in human blood ex vivo by 
      human granulocyte-macrophage colony-stimulating factor and tumor necrosis 
      factor-alpha.
PG  - 696-704
AB  - BACKGROUND: Previous studies reported the priming effects of 
      granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis 
      factor-alpha (TNF alpha) on leukotriene synthesis by isolated polymorphonuclear 
      leukocytes; however, little is known as of yet of these biologic effects of the 
      two cytokines in a physiologic environment. EXPERIMENTAL DESIGN: In this study, 
      we investigate the effects of GM-CSF and TNF alpha on the synthesis of 
      5-lipoxygenase (5-LO) products in heparinized blood stimulated ex vivo, using 
      reverse phase high performance liquid chromatography analysis of deproteinized 
      plasma samples. RESULTS: Stimulation of blood with f-Met-Leu-Phe resulted in the 
      accumulation of up to 30 pmol of 5-LO products/ml of plasma. Preincubation of 
      blood with 100 pM GM-CSF or 1.2 nM (200 units/ml) TNF alpha for 30 minutes at 37 
      degrees C before stimulation with f-Met-Leu-Phe resulted in a marked enhancement 
      (> 5-fold) of the synthesis of leukotriene B4 and 5(S)-hydroxyeicosatetraenoic 
      acid, which were formed in equivalent amounts. GM-CSF and TNF alpha priming 
      activities were detectable at concentrations as low as 3 pM and 6 pM (1 unit/ml), 
      respectively. The preincubation times required for optimal priming by GM-CSF and 
      TNF alpha were different (40 and 10 minutes, respectively), and the effects of 
      the two cytokines on leukotriene B4 and 5(S)-hydroxyeicosatetraenoic acid 
      synthesis were additive, suggesting different priming mechanisms. The synthesis 
      of 5-LO products in primed blood was also induced by platelet-activating factor, 
      the complement fragment C5a, the particulate stimulus zymosan, and the ionophore 
      A23187, but not by interleukin-8. Polymorphonuclear leukocytes and mononuclear 
      cells accounted for 80% and 20% of the synthesis of 5-LO products, respectively. 
      CONCLUSIONS: These data demonstrate that GM-CSF and TNF alpha exert very potent 
      priming effects on the biosynthesis of 5-LO products in whole blood stimulated by 
      various stimuli and strongly support that these cytokines could be important 
      modulators of lipid mediator synthesis in physiologic and pathophysiologic 
      conditions.
FAU - Palmantier, R
AU  - Palmantier R
AD  - Centre de Recherche en Inflammation, Immunologie et Rhumatologie, Centre 
      Hospitalier, Universite Laval, Quebec, Canada.
FAU - Surette, M E
AU  - Surette ME
FAU - Sanchez, A
AU  - Sanchez A
FAU - Braquet, P
AU  - Braquet P
FAU - Borgeat, P
AU  - Borgeat P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Interleukin-8)
RN  - 0 (Platelet Activating Factor)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 37H9VM9WZL (Calcimycin)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 80295-54-1 (Complement C5a)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - 9010-72-4 (Zymosan)
RN  - EC 1.13.11.34 (Arachidonate 5-Lipoxygenase)
SB  - IM
MH  - Arachidonate 5-Lipoxygenase/*blood
MH  - Calcimycin/pharmacology
MH  - Complement C5a/pharmacology
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/*pharmacology
MH  - Humans
MH  - Interleukin-8/pharmacology
MH  - Kinetics
MH  - Monocytes/drug effects/enzymology/*metabolism
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/drug effects/enzymology/*metabolism
MH  - Platelet Activating Factor/pharmacology
MH  - Recombinant Proteins/pharmacology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Zymosan/pharmacology
EDAT- 1994/05/01 00:00
MHDA- 1994/05/01 00:01
CRDT- 1994/05/01 00:00
PHST- 1994/05/01 00:00 [pubmed]
PHST- 1994/05/01 00:01 [medline]
PHST- 1994/05/01 00:00 [entrez]
PST - ppublish
SO  - Lab Invest. 1994 May;70(5):696-704.