Platelet-neutrophil interactions. (12S)-hydroxyeicosatetraen-1,20-dioic acid

A new eicosanoid synthesized by unstimulated neutrophils from (12S)-20-dihydroxyeicosatetraenoic acid

A. J. Marcus, L. B. Safier, H. L. Ullman, N. Islam, M. J. Broekman, J R Falck, S. Fischer, C. Von Schacky

Research output: Contribution to journalArticle

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Abstract

In the course of a cell-cell interaction, 12-HETE (12-hydroxy-5,8,10,14-eicosatetraenoic acid), the arachidonic acid lipoxygenase product released from stimulated platelets, is metabolized by a cytochrome P-450 enzyme system in unstimulated neutrophils to 12,20-DiHETE (12,20-dihydroxy-5,8,10,14-eicosatetraenoic acid). This report describes time-dependent formation of a new eicosanoid by unstimulated neutrophils exposed to 12-HETE, which is more polar than 12,20-DiHETE (reversed-phase high performance liquid chromatography). Time course studies indicated that the precursor compound of this new eicosanoid was 12,20-DiHETE. This was determined by incubation of purified 12,20-DiHETE with neutrophils, which resulted in a progressive decrease in 12,20-DiHETE as formation of the polar metabolite increased. In the absence of neutrophils, 12,20-DiHETE was quantitatively unchanged. The new metabolite of 12,20-DiHETE was identified as 12-hydroxyeicosatetraen-1,20-dioic acid, based upon its UV spectrum, cochromatography with a chemically synthesized standard in both high performance liquid chromatography and thin layer chromatorgraphy systems, and gas chromatography-mass spectrometry. Formation of 12-HETE-1,20-dioic acid was partially inhibited by 20-hydroxy-LTB4. This indicated that the neutrophil dehydrogenase responsible for further metabolism of 12,20-DiHETE may also be involved in conversion of 20-hydroxy-LTB4 to 20-carboxy-LTB4. The 12,20-DiHETE dehydrogenase enzyme system specifically requires NAD as cofactor and has subcellular components in both cytosolic and microsomal fractions which are synergistic in their activity. These results provide additional evidence for the occurrence of multicellular metabolic events during hemostasis, thrombosis, and the inflammatory response.

Original languageEnglish (US)
Pages (from-to)2223-2229
Number of pages7
JournalJournal of Biological Chemistry
Volume263
Issue number5
StatePublished - 1988

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Eicosanoids
Platelets
Neutrophils
Blood Platelets
Acids
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Leukotriene B4
High performance liquid chromatography
Metabolites
Oxidoreductases
High Pressure Liquid Chromatography
Arachidonate Lipoxygenases
12,20-dihydroxy-5,8,10,14-eicosatetraenoic acid
Time and motion study
Reverse-Phase Chromatography
Hemostasis
Metabolism
Cell Communication
Gas chromatography
NAD

ASJC Scopus subject areas

  • Biochemistry

Cite this

Platelet-neutrophil interactions. (12S)-hydroxyeicosatetraen-1,20-dioic acid : A new eicosanoid synthesized by unstimulated neutrophils from (12S)-20-dihydroxyeicosatetraenoic acid. / Marcus, A. J.; Safier, L. B.; Ullman, H. L.; Islam, N.; Broekman, M. J.; Falck, J R; Fischer, S.; Von Schacky, C.

In: Journal of Biological Chemistry, Vol. 263, No. 5, 1988, p. 2223-2229.

Research output: Contribution to journalArticle

Marcus, A. J. ; Safier, L. B. ; Ullman, H. L. ; Islam, N. ; Broekman, M. J. ; Falck, J R ; Fischer, S. ; Von Schacky, C. / Platelet-neutrophil interactions. (12S)-hydroxyeicosatetraen-1,20-dioic acid : A new eicosanoid synthesized by unstimulated neutrophils from (12S)-20-dihydroxyeicosatetraenoic acid. In: Journal of Biological Chemistry. 1988 ; Vol. 263, No. 5. pp. 2223-2229.
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abstract = "In the course of a cell-cell interaction, 12-HETE (12-hydroxy-5,8,10,14-eicosatetraenoic acid), the arachidonic acid lipoxygenase product released from stimulated platelets, is metabolized by a cytochrome P-450 enzyme system in unstimulated neutrophils to 12,20-DiHETE (12,20-dihydroxy-5,8,10,14-eicosatetraenoic acid). This report describes time-dependent formation of a new eicosanoid by unstimulated neutrophils exposed to 12-HETE, which is more polar than 12,20-DiHETE (reversed-phase high performance liquid chromatography). Time course studies indicated that the precursor compound of this new eicosanoid was 12,20-DiHETE. This was determined by incubation of purified 12,20-DiHETE with neutrophils, which resulted in a progressive decrease in 12,20-DiHETE as formation of the polar metabolite increased. In the absence of neutrophils, 12,20-DiHETE was quantitatively unchanged. The new metabolite of 12,20-DiHETE was identified as 12-hydroxyeicosatetraen-1,20-dioic acid, based upon its UV spectrum, cochromatography with a chemically synthesized standard in both high performance liquid chromatography and thin layer chromatorgraphy systems, and gas chromatography-mass spectrometry. Formation of 12-HETE-1,20-dioic acid was partially inhibited by 20-hydroxy-LTB4. This indicated that the neutrophil dehydrogenase responsible for further metabolism of 12,20-DiHETE may also be involved in conversion of 20-hydroxy-LTB4 to 20-carboxy-LTB4. The 12,20-DiHETE dehydrogenase enzyme system specifically requires NAD as cofactor and has subcellular components in both cytosolic and microsomal fractions which are synergistic in their activity. These results provide additional evidence for the occurrence of multicellular metabolic events during hemostasis, thrombosis, and the inflammatory response.",
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T1 - Platelet-neutrophil interactions. (12S)-hydroxyeicosatetraen-1,20-dioic acid

T2 - A new eicosanoid synthesized by unstimulated neutrophils from (12S)-20-dihydroxyeicosatetraenoic acid

AU - Marcus, A. J.

AU - Safier, L. B.

AU - Ullman, H. L.

AU - Islam, N.

AU - Broekman, M. J.

AU - Falck, J R

AU - Fischer, S.

AU - Von Schacky, C.

PY - 1988

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N2 - In the course of a cell-cell interaction, 12-HETE (12-hydroxy-5,8,10,14-eicosatetraenoic acid), the arachidonic acid lipoxygenase product released from stimulated platelets, is metabolized by a cytochrome P-450 enzyme system in unstimulated neutrophils to 12,20-DiHETE (12,20-dihydroxy-5,8,10,14-eicosatetraenoic acid). This report describes time-dependent formation of a new eicosanoid by unstimulated neutrophils exposed to 12-HETE, which is more polar than 12,20-DiHETE (reversed-phase high performance liquid chromatography). Time course studies indicated that the precursor compound of this new eicosanoid was 12,20-DiHETE. This was determined by incubation of purified 12,20-DiHETE with neutrophils, which resulted in a progressive decrease in 12,20-DiHETE as formation of the polar metabolite increased. In the absence of neutrophils, 12,20-DiHETE was quantitatively unchanged. The new metabolite of 12,20-DiHETE was identified as 12-hydroxyeicosatetraen-1,20-dioic acid, based upon its UV spectrum, cochromatography with a chemically synthesized standard in both high performance liquid chromatography and thin layer chromatorgraphy systems, and gas chromatography-mass spectrometry. Formation of 12-HETE-1,20-dioic acid was partially inhibited by 20-hydroxy-LTB4. This indicated that the neutrophil dehydrogenase responsible for further metabolism of 12,20-DiHETE may also be involved in conversion of 20-hydroxy-LTB4 to 20-carboxy-LTB4. The 12,20-DiHETE dehydrogenase enzyme system specifically requires NAD as cofactor and has subcellular components in both cytosolic and microsomal fractions which are synergistic in their activity. These results provide additional evidence for the occurrence of multicellular metabolic events during hemostasis, thrombosis, and the inflammatory response.

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