Human dendritic cells are a physiological source of the chemotactic arachidonic acid metabolite 5-oxo-eicosatetraenoic acid

• Published in: Inflammation research Vol. 49; no. 11; pp. 633 - 638
• Main Authors: Zimpfer, U, Dichmann, S, Termeer, C C, Simon, J C, Schröder, J M, Norgauer, J
• Format: Journal Article
• Language: English
• Published: Switzerland 01-11-2000
• Subjects: 5-hydroxyeicosatetraenoic acid; 5-oxo-eicosatetraenoic acid; arachidonic acid; Arachidonic Acids - biosynthesis; Calcimycin - pharmacology; Chemotactic Factors - biosynthesis; Chromatography, High Pressure Liquid; complement component C5a; Dendritic Cells - drug effects; Dendritic Cells - metabolism; Humans; Hydroxyeicosatetraenoic Acids - metabolism; Ionophores - pharmacology; Neutrophils - drug effects; Neutrophils - metabolism; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s000110050641

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.
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.
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.
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.