Human dendritic cells are a physiological source of the chemotactic arachidonic acid metabolite 5-oxo-eicosatetraenoic acid.
OBJECTIVE
The arachidonic acid metabolite, 5-oxo-eicosatetraenoic acid (5-oxo-ETE), is a potent chemotaxin for neutrophils and eosinophils. The aim of this study was to identify physiological conditions and stimulators of 5-oxo-ETE synthesis, because no such conditions have yet been identified.


METHODS
Human neutrophils and monocyte-derived dendritic cells were prepared and 5-oxo-ETE synthesis analyzed using precolumn/reversed-phase HPLC under different conditions and with several physiological and unphysiological stimuli.


RESULTS
Incubation of neutrophils with 5-hydroxyeicosatetraenoic acid (5-HETE) resulted in the synthesis of about 3.4 nM 5-oxo-ETE per 10(6) cells in 1 ml under optimal conditions. The synthesis was enhanced about 8-fold with the unphysiological stimuli calcium ionophore A23187 and phorbol 12-myristate 13-acetate (PMA). No significant effect was observed with different physiological activators. Under optimal conditions, human dendritic cells produced about 50 nM 5-oxo-ETE per 10(6) cells in 1 ml. The synthesis could be increased with PMA and A23187 by about 50%. Again, no effect could be observed with physiological agents for dendritic cells such as complement fragment C5a, platelet activating factor, N-formyl peptides and interleukin-5.


CONCLUSIONS
These data identified dendritic cells as the only yet known physiological source of relevant amounts of 5-oxo-ETE. This suggests a regulatory function of dendritic cells in the induction of inflammatory neutrophil and eosinophil infiltration caused by 5-oxo-eicosatetraenoic acid.
Zimpfer
U
U
Abteilung Experimentelle Dermatologie, University of Freiburg, Germany. zimpfer@haut-ukl.uni-freiburg-de
Dichmann
S
S
Termeer
C C
CC
Simon
J C
JC
Schröder
J M
JM
Norgauer
J
J
D001095:Arachidonic Acids / Q000096:biosynthesis*; D000001:Calcimycin / Q000494:pharmacology; D002630:Chemotactic Factors / Q000096:biosynthesis*; D002851:Chromatography, High Pressure Liquid; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001095:Arachidonic Acids; D002630:Chemotactic Factors; D006893:Hydroxyeicosatetraenoic Acids; D007476:Ionophores; C080828:5-oxo-6,8,11,14-eicosatetraenoic acid; D000001:Calcimycin; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D013755:Tetradecanoylphorbol Acetate