Identification of 5-oxo-15-hydroxy-6,8,11,13-eicosatetraenoic acid as a novel and potent human eosinophil chemotactic eicosanoid.
Incubation of human eosinophils with arachidonic acid led to the formation of a novel and potent eosinophil chemotactic lipid (ECL) (Morita, E., Schröder, J.-M., and Christophers, E. (1990) J. Immunol. 144, 1893-1900). To test the working hypothesis of whether ECL could have been formed via eosinophil-arachidonic acid 15-lipoxygenase we investigated whether other arachidonic acid 15-lipoxygenases such as soybean lipoxygenase I catalyze formation of a similar ECL. In the presence of hemoproteins and soybean lipoxygenase I arachidonic acid is converted to an ECL, which has physicochemical properties similar to those found for the eosinophil-derived ECL. Purification of this ECL by high performance liquid chromatography revealed that ECL is structurally different from well known eosinophil chemotactic eicosanoids such as leukotriene B4, 5,15-(6E,8Z,11Z,13E)-dihydroxyeicosatetraenoic acid (5,15-diHETE), and (8S,15S)-(5Z,9E,11Z,13E)-dihydroxyeicosatetra eno ic acid ((8S,15S)-diHETE). UV spectra of this ECL with absorbance maxima at 230 and 278 nm revealed the presence of two independent chromophores such as a conjugated oxodiene and a conjugated diene. Catalytic hydrogenation of ECL methyl ester led to the formation of 5,15-dihydroxyarachidic acid methyl ester. Reduction of ECL with sodium borohydride produced a product which is identical with authentic (5S,15S)-(6E,8Z,11Z,13E)-diHETE. Formation of an ECL monomethoxime derivative supports the conclusion that this highly potent eosinophil chemotactic eicosanoid is structurally identical with 5-oxo-15-hydroxy-6,8,11,13-eicosatetraenoic acid.
Schwenk
U
U
Department of Dermatology, University of Kiel, Federal Republic of Germany.
Morita
E
E
Engel
R
R
Schröder
J M
JM
D016718:Arachidonic Acid / Q000378:metabolism; D002631:Chemotactic Factors, Eosinophil / Q000378:metabolism / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D008084:Lipoxygenase / Q000378:metabolism; D013058:Mass Spectrometry; D013056:Spectrophotometry, Ultraviolet
D002631:Chemotactic Factors, Eosinophil; D006893:Hydroxyeicosatetraenoic Acids; C075441:5-oxo-15-hydroxy-6,8,11,13-eicosatetraenoic acid; D016718:Arachidonic Acid; D008084:Lipoxygenase