PMID- 8691070
OWN - NLM
STAT- MEDLINE
DCOM- 19960829
LR  - 20190516
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 59
IP  - 6
DP  - 1996 Jun
TI  - Synthesis of 5-oxo-6,8,11,14-eicosatetraenoic acid by human monocytes and 
      lymphocytes.
PG  - 847-54
AB  - We recently demonstrated that the arachidonate metabolite 
      5(S)-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) is converted by a highly 
      specific dehydrogenase in human neutrophils to 5-oxo-6,8,11,14-eicosatetraenoic 
      acid (5-oxo-ETE), which is a potent stimulator of these cells. The objective of 
      this study was to determine whether 5-oxo-ETE is also formed by monocytes and 
      lymphocytes. Human monocytes (74 +/- 2% pure) and lymphocytes (86 +/- 1% pure) 
      were prepared by successive centrifugations of leukocytes over Ficoll-Paque and 
      Percoll. Both cell types converted 5-HETE to a single major product, which was 
      identified as 5-oxo-ETE. The formation of 5-oxo-ETE was stimulated about twofold 
      by phorbol myristate acetate (PMA; 30 nM). Dehydrogenase activity in monocyte 
      fractions did not appear to be due to platelet contamination, since depletion of 
      platelets did not reduce enzyme activity. The dehydrogenase was localized in 
      membrane fractions from monocytes and required NADP+ as a cofactor. It was 
      specific for eicosanoids containing a 5S-hydroxyl group followed by a 6-trans 
      double bond. We also investigated the formation of 5-oxo-ETE from endogenous 
      arachidonic acid by monocytes. 5-Oxo-ETE, 5-HETE, and leukotriene B4 (LTB4) were 
      present in comparable amounts after incubation of these cells with A23187. PMA 
      (EC50 approximately 4 nM) stimulated the formation of 5-oxo-ETE and 5-HETE and, 
      to a lesser extent, LTB4. Although monocytes released considerably less 5-HETE 
      and LTB4 than neutrophils, they released comparable amounts of 5-oxo-ETE. Unlike 
      neutrophils, monocytes did not convert any of these substances to detectable 
      amounts of omega-oxidation products. Although lymphocytes were capable of 
      converting 5-HETE to 5-oxo-ETE, they released little or no 5-lipoxygenase 
      products in response to A23187. We conclude that monocytes have a high capacity 
      to synthesize 5-oxo-ETE and that its formation is stimulated by activation of 
      protein kinase C.
FAU - Zhang, Y
AU  - Zhang Y
AD  - Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
FAU - Styhler, A
AU  - Styhler A
FAU - Powell, W S
AU  - Powell WS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Hydroxyeicosatetraenoic Acids)
RN  - 37H9VM9WZL (Calcimycin)
RN  - 467RNW8T91 (5-hydroxy-6,8,11,14-eicosatetraenoic acid)
RN  - EC 1.1.- (Alcohol Oxidoreductases)
RN  - EC 1.1.1.- (5-hydroxyeicosanoid dehydrogenase)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Alcohol Oxidoreductases/metabolism
MH  - Calcimycin/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Hydroxyeicosatetraenoic Acids/*biosynthesis
MH  - Lymphocytes/*metabolism
MH  - Monocytes/*metabolism
MH  - Neutrophils/enzymology
MH  - Tetradecanoylphorbol Acetate/pharmacology
EDAT- 1996/06/01 00:00
MHDA- 1996/06/01 00:01
CRDT- 1996/06/01 00:00
PHST- 1996/06/01 00:00 [pubmed]
PHST- 1996/06/01 00:01 [medline]
PHST- 1996/06/01 00:00 [entrez]
AID - 10.1002/jlb.59.6.847 [doi]
PST - ppublish
SO  - J Leukoc Biol. 1996 Jun;59(6):847-54. doi: 10.1002/jlb.59.6.847.