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PMID: 8666921 Published · ppublish English Journal Article

5(S),15(S)-dihydroxyeicosatetraenoic acid and lipoxin generation in human polymorphonuclear cells: dual specificity of 5-lipoxygenase towards endogenous and exogenous precursors.

The Journal of experimental medicine ·Vol. 183 ·No. 4 ·1996-04-01 ·Pages 1633-43

Chavis C, Vachier I, Chanez P, Bousquet J, Godard P

Abstract

5-Lipoxygenase activation of human blood polymorphonuclear cells (PMN) from asthmatic patients (asthmatics) was studied to investigate whether differences may exist with healthy subjects (controls). The respective cell capacities to produce lipoxins (LXs), leukotrienes, and 5(S), 15(S)-dihydroxyeicosatetraenoic acid [5(S),15(S)-diHETE] were compared under in vitro stimulation by ionophore A23187, with or without exogenous 15(S)-hydroxyeicosatetraenoic acid [15(S)-diHETE]. Eicosanoids were analyzed by elution with an isocratic reverse-phase high performance liquid chromatography system, and their profiles, detected by simultaneous monitoring at 302, 280, and 246 nm, were evaluated on the basis of chromatographic behavior: UV spectral characteristics and coelution with synthetic standards. In the presence of exogenous 15(S)-HETE, human PMN were able to produce LXs and 5(S),15(S)-diHETE, PMN from asthmatics were able to produce 5(S), 5(S),15(S)-diHETE, and LXs from endogenous sources, whereas in the same experimental conditions, no detectable amounts of these compounds were released by PMN from controls. The levels of 5(S),15(S)-diHETE, and LXs biosynthesized from endogenous arachidonic acid were highly correlated. Two different LX patterns were observed involving two possible metabolic pathways: (a) via the intermediate 5,6-epoxytetraene alone for LXs generation from exogenous 15(S)-HETE; and (b) via 5,6- and/or 14,15-epoxytetraenes leading to the formation of an enzyme-bound delocalized carbocation for LXs generation from endogenous arachidonate, respectively. The enhanced 5-lipoxygenase activation of blood PMN from asthmatics and the metabolism of exogenous 15(S)-HETE may reflect a priming induced by various mediators released from environmental cells, and could be considered as a model of transcellular signalization between PMN and endothelial cells.

MeSH Terms
Arachidonate 5-Lipoxygenase/metabolism Arachidonic Acids/biosynthesis Asthma/metabolism Calcimycin/pharmacology Chromatography, High Pressure Liquid Female Humans Hydroxyeicosatetraenoic Acids/biosynthesis,metabolism,pharmacology Male Models, Biological Neutrophil Activation/drug effects,physiology Substrate Specificity
Chemicals
Arachidonic Acids Hydroxyeicosatetraenoic Acids Calcimycin 15-hydroxy-5,8,11,13-eicosatetraenoic acid 5,15-dihydroxy-6,8,11,13-eicosatetraenoic acid Arachidonate 5-Lipoxygenase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Chavis C
Clinique des Maladies Respiratoires, INSERM U 454, Montpellier, France.
Vachier I
Chanez P
Bousquet J
Godard P
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.183.4.1633
Published
1996-04-01
Pages
1633-43
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192510
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.183.4.1633 PMC Full Text View journal details
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