Human polymorphonuclear leukocytes express prostaglandin h synthase-2 when stimulated with lipopolysaccharide (LPS)

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Abstract

The synthesis of prostanoids is regulated by prostaglandin H synthases (PHS) (cyclooxy genäse), catalyzing the conversion of arachidonic acid to PGH2- PHS is the target of aspirin and other nonsteroidal anti-inflammatory agents. An inducible form, PHS-2, has recently been identified. It differs from Ihe constitutive form, PHS-1, in sequence, inhibition by anti-inflammatory agenis, cell distribution and other features. We report for the first time that human polymorphonuclear leukocytes (PMNs) express PHS-2 when stimulated by lipopolysaccharide (LPS). By Western analysis, PHS-2 was not detectable in freshly-isolated human PMNs. Levels of the protein increased in a time- and concentration-dependent fashion when PMNs were exposed to LPS. Expression of PHS-2 was paralleled by secretion of prostaglandin E2, suggesting that the enzyme influences the prostanoids produced by these cells. Human monocytes, monocytic cell lines, and human monocyte-derived macrophages also expressed PHS-2 when stimulated with LPS. The time course of LPS induced PHS-2 was different between freshly-isolated PMNs and mor/>,ytes: in PMNs, levels peaked !it 3 hr. and returned to baseline by 18 hr., whereas levels continuously increased in monocytes over a 24 hr. period. The time course in stimulated macrophages differed from that in both PMNs and monocytes, indicating that PHS-2 expression is differentially regulated in myeloid cells of different lineages and degrees of maturation. Consistent with this, interleukin (IL)-IO, which has been reponed to suppress LPS induced PHS-2 expression in monocytes, had no effect on LPS induced PHS-2 expression in PMNs. The level of PHS-2 in LPS-stimulated PMNs was enhanced by treatment of the cells wiih tumor necrosis factor-a, IL-8, and IL-1B, These experiments show that PMNs, a cell thought to have little or no protein synthetic potential until recently, express PHS-2, Thus, they may actively influence the eicosanoid composition of the acute inflammatory milieu.

Original languageEnglish (US)
JournalJournal of Investigative Medicine
Volume44
Issue number3
StatePublished - Jan 1 1996

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Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases
Lipopolysaccharides
Neutrophils
Monocytes
Macrophages
Interleukins
Prostaglandins
Cells
Prostaglandin H2
Cyclooxygenase 1
Eicosanoids
Non-Steroidal Anti-Inflammatory Agents
Cell Lineage
Myeloid Cells
Interleukin-8
Dinoprostone
Arachidonic Acid
Aspirin
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

@article{7f6cb8703e9743c1bd5969bb6dc485ae,
title = "Human polymorphonuclear leukocytes express prostaglandin h synthase-2 when stimulated with lipopolysaccharide (LPS)",
abstract = "The synthesis of prostanoids is regulated by prostaglandin H synthases (PHS) (cyclooxy gen{\"a}se), catalyzing the conversion of arachidonic acid to PGH2- PHS is the target of aspirin and other nonsteroidal anti-inflammatory agents. An inducible form, PHS-2, has recently been identified. It differs from Ihe constitutive form, PHS-1, in sequence, inhibition by anti-inflammatory agenis, cell distribution and other features. We report for the first time that human polymorphonuclear leukocytes (PMNs) express PHS-2 when stimulated by lipopolysaccharide (LPS). By Western analysis, PHS-2 was not detectable in freshly-isolated human PMNs. Levels of the protein increased in a time- and concentration-dependent fashion when PMNs were exposed to LPS. Expression of PHS-2 was paralleled by secretion of prostaglandin E2, suggesting that the enzyme influences the prostanoids produced by these cells. Human monocytes, monocytic cell lines, and human monocyte-derived macrophages also expressed PHS-2 when stimulated with LPS. The time course of LPS induced PHS-2 was different between freshly-isolated PMNs and mor/>,ytes: in PMNs, levels peaked !it 3 hr. and returned to baseline by 18 hr., whereas levels continuously increased in monocytes over a 24 hr. period. The time course in stimulated macrophages differed from that in both PMNs and monocytes, indicating that PHS-2 expression is differentially regulated in myeloid cells of different lineages and degrees of maturation. Consistent with this, interleukin (IL)-IO, which has been reponed to suppress LPS induced PHS-2 expression in monocytes, had no effect on LPS induced PHS-2 expression in PMNs. The level of PHS-2 in LPS-stimulated PMNs was enhanced by treatment of the cells wiih tumor necrosis factor-a, IL-8, and IL-1B, These experiments show that PMNs, a cell thought to have little or no protein synthetic potential until recently, express PHS-2, Thus, they may actively influence the eicosanoid composition of the acute inflammatory milieu.",
author = "Maloney, {Christopher G}",
year = "1996",
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day = "1",
language = "English (US)",
volume = "44",
journal = "Journal of Investigative Medicine",
issn = "1081-5589",
publisher = "Lippincott Williams and Wilkins",
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T1 - Human polymorphonuclear leukocytes express prostaglandin h synthase-2 when stimulated with lipopolysaccharide (LPS)

AU - Maloney, Christopher G

PY - 1996/1/1

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N2 - The synthesis of prostanoids is regulated by prostaglandin H synthases (PHS) (cyclooxy genäse), catalyzing the conversion of arachidonic acid to PGH2- PHS is the target of aspirin and other nonsteroidal anti-inflammatory agents. An inducible form, PHS-2, has recently been identified. It differs from Ihe constitutive form, PHS-1, in sequence, inhibition by anti-inflammatory agenis, cell distribution and other features. We report for the first time that human polymorphonuclear leukocytes (PMNs) express PHS-2 when stimulated by lipopolysaccharide (LPS). By Western analysis, PHS-2 was not detectable in freshly-isolated human PMNs. Levels of the protein increased in a time- and concentration-dependent fashion when PMNs were exposed to LPS. Expression of PHS-2 was paralleled by secretion of prostaglandin E2, suggesting that the enzyme influences the prostanoids produced by these cells. Human monocytes, monocytic cell lines, and human monocyte-derived macrophages also expressed PHS-2 when stimulated with LPS. The time course of LPS induced PHS-2 was different between freshly-isolated PMNs and mor/>,ytes: in PMNs, levels peaked !it 3 hr. and returned to baseline by 18 hr., whereas levels continuously increased in monocytes over a 24 hr. period. The time course in stimulated macrophages differed from that in both PMNs and monocytes, indicating that PHS-2 expression is differentially regulated in myeloid cells of different lineages and degrees of maturation. Consistent with this, interleukin (IL)-IO, which has been reponed to suppress LPS induced PHS-2 expression in monocytes, had no effect on LPS induced PHS-2 expression in PMNs. The level of PHS-2 in LPS-stimulated PMNs was enhanced by treatment of the cells wiih tumor necrosis factor-a, IL-8, and IL-1B, These experiments show that PMNs, a cell thought to have little or no protein synthetic potential until recently, express PHS-2, Thus, they may actively influence the eicosanoid composition of the acute inflammatory milieu.

AB - The synthesis of prostanoids is regulated by prostaglandin H synthases (PHS) (cyclooxy genäse), catalyzing the conversion of arachidonic acid to PGH2- PHS is the target of aspirin and other nonsteroidal anti-inflammatory agents. An inducible form, PHS-2, has recently been identified. It differs from Ihe constitutive form, PHS-1, in sequence, inhibition by anti-inflammatory agenis, cell distribution and other features. We report for the first time that human polymorphonuclear leukocytes (PMNs) express PHS-2 when stimulated by lipopolysaccharide (LPS). By Western analysis, PHS-2 was not detectable in freshly-isolated human PMNs. Levels of the protein increased in a time- and concentration-dependent fashion when PMNs were exposed to LPS. Expression of PHS-2 was paralleled by secretion of prostaglandin E2, suggesting that the enzyme influences the prostanoids produced by these cells. Human monocytes, monocytic cell lines, and human monocyte-derived macrophages also expressed PHS-2 when stimulated with LPS. The time course of LPS induced PHS-2 was different between freshly-isolated PMNs and mor/>,ytes: in PMNs, levels peaked !it 3 hr. and returned to baseline by 18 hr., whereas levels continuously increased in monocytes over a 24 hr. period. The time course in stimulated macrophages differed from that in both PMNs and monocytes, indicating that PHS-2 expression is differentially regulated in myeloid cells of different lineages and degrees of maturation. Consistent with this, interleukin (IL)-IO, which has been reponed to suppress LPS induced PHS-2 expression in monocytes, had no effect on LPS induced PHS-2 expression in PMNs. The level of PHS-2 in LPS-stimulated PMNs was enhanced by treatment of the cells wiih tumor necrosis factor-a, IL-8, and IL-1B, These experiments show that PMNs, a cell thought to have little or no protein synthetic potential until recently, express PHS-2, Thus, they may actively influence the eicosanoid composition of the acute inflammatory milieu.

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