12S,20-dihydroxyicosatetraenoic acid: a new icosanoid synthesized by neutrophils from 12S-hydroxyicosatetraenoic acid produced by thrombin- or collagen-stimulated platelets.

Marcus, Aaron J.; Safier, Lenore B.; Ullman, H L; Broekman, M. Johan; Islam, Naziba; Oglesby, Thomas D.; Gorman, Robert R.

doi:10.1073/pnas.81.3.903

Cited by 127 publications

(40 citation statements)

References 11 publications

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“…It was also demonstrated that PMNL stimulated with the ionophore A23187 in the presence of platelets transform platelet-derived 12S-hydroxy-5, 8,10,14-(Z,Z,E,Z)-eicosatetraenoic acid (12-HETE) into 5S,12S-dihydroxy-6,8,10,14(E,Z,E,Z)-eicosatetraenoic acid (5S, 12S-DiHETE) Marcus et al, 1982), and arachidonic acid into LTB4 (Marcus et al, 1982) via the 5-lipoxygenase pathway. In addition, 12-HETE synthesized in platelets is metabolized to 12S,8,10,14(Z,Z,E, by unstimulated neutrophils (Marcus et al, 1984). In previous studies we have also shown that incubation of PMNL with high concentration of exogenous arachidonic acid in the presence of platelelets results in increased synthesis of 5-lipoxygenase products.…”

Section: Introductionmentioning

confidence: 79%

“…Figure 1 shows that activated platelet and PMNL mixtures produced 55,12S-DiHETE, which is a product of the double dioxygenation of arachidonic acid by the 5-and 12-lipoxygenases Marcus et al, 1982). The product of the co-oxidation of the 5S,12S-DiHETE in the PMNL, the 5S,12S,20-TriHETE (Lindgren et al, 1981), was always formed in substantial amounts, while the 12-HETE metabolite, 12,20-DiHETE (Marcus et al, 1984) was also present but in smaller amounts. The mechanism of formation of these three products of platelet-PMNL interaction have been discussed previously (Lindgren et al, 1981;Marcus et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

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Thrombin‐activated platelets promote leukotriene B₄ synthesis in polymorphonuclear leucocytes stimulated by physiological agonists

Palmantier

Borgeat

1991

British J Pharmacology

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The addition of 2 × 108 human platelets to 8 × 106 polymorphonuclear leucocytes (PMNL) incubated in presence of 2.5 u ml−1 thrombin and 0.1 μm N‐formyl‐Met‐Leu‐Phe (FMLP) (or C5a or PAF) led to enhancement of leukotriene B4 (LTB4) synthesis by the PMNL (measured by h.p.l.c. as 20‐hydroxy‐ and 20‐carboxy‐LTB4) from 4 ± 1 pmol (in absence of platelets) to 26 ± 4 pmol (mean ± s.e.mean, n = 9). Platelets and thrombin were both essential for the enhancement of LTB4 synthesis. Platelets also caused enhancement of LTB4 synthesis from (30 ± 12 to 134 ± 25 pmol, n = 6) when PMNL pretreated with granulocyte‐macrophage colony‐stimulating factor were used in similar experiments. Enhancement of LTB4 synthesis was also observed (from 5 ± 1.5 to 26.5 ± 5 pmol, n = 9) when the supernatants of thrombin‐activated platelet suspensions were added to FMLP‐stimulated PMNL. Supernatants of platelet suspensions activated by thrombin in presence of cyclo‐oxygenase and 12‐lipoxygenase inhibitors led to greater enhancement (from 5 ± 3 to 153.5 ± 27.5 pmol, n = 3) of LTB4 synthesis by FMLP‐stimulated PMNL, suggesting that arachidonic acid itself, rather than its metabolites was responsible for the effects of platelets. Addition of arachidonic acid to FMLP‐stimulated PMNL at a concentration comparable to that measured in thrombin‐activated platelet supernatants (0.2 ± 0.025 μm, n = 6) mimicked the effect of platelets or platelet supernatants on LTB4 synthesis in FMLP‐activated PMNL. The present data indicate that under conditions of cell activation by physiological agonists, platelets can significantly increase the formation of the proinflammatory compound LTB4 in PMNL by providing arachidonic acid. These data lend support to the concept that platelet‐PMNL interactions could modulate the inflammatory process.

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Section: Introductionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Thrombin‐activated platelets promote leukotriene B₄ synthesis in polymorphonuclear leucocytes stimulated by physiological agonists

Palmantier

Borgeat

1991

British J Pharmacology

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“…Accordingly, it is likely that lipoxygenase metabolites are involved in plateletmediated leucopenia following antigen challenge. It has been established that platelets possess a lipoxygenase which transforms the unstable metabolite 12-hydroperoxy-eicosatbtraenoic acid (12-HPETE) into 12-hydroxyeicosatetraenoic acid (12-HETE), the latter being a chemotactic agent for neutrophils and eosinophils (Marcus et al, 1984). In addition, the coincubation of platelets and leucocytes in the presence of arachidonic acid induced the release of 12-HPETE from platelets which, in turn, activated the 5-lipoxygenase of leucocytes leading to the production of 5-HETE (Maclouf et al, 1982).…”

Section: Discussionmentioning

confidence: 99%

Antigen induces leucopenia in non‐immunised guinea‐pigs injected with platelets from actively sensitized animals

Pretolani¹,

Randon

Vargaftig

1990

British J Pharmacology

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Ovalbumin administration to animals injected with 0.5–5 × 106 washed platelets μl−1 from actively sensitized animals induced a marked decrease (maximum of around 50% at 60 min) in the number of circulating leucocytes, whereas platelet counts were unaffected. The intensity of the decrease in leucocyte counts was dependent upon the concentration of the injected platelets. No drop in leucocyte counts was measured upon antigen challenge of guinea‐pigs injected with platelets from non‐sensitized animals. This phenomenon was unaffected by pretreatment of the recipient animals with a platelet‐activating factor (PAF) antagonist WEB 2086 (3 mg kg−1 i.v.) but was markedly reduced (around 50% inhibition) by the anti‐allergic drug nedocromil sodium (100 mg kg−1 i.v.). By contrast, indomethacin (5 mg kg−1 i.v.) caused a significant (P < 0.01) enhancement of the antigen‐induced leucopenia, whereas the mixed cyclooxygenase and lipoxygenase inhibitor, BW 755C (10 mg kg−1 i.v.) suppressed the drop in leucocyte counts evoked by ovalbumin administration. These results indicate that platelets from actively sensitized guinea‐pigs transferred to normal animals still responds to the specific antigen with the activation of circulating leucocytes. This phenomenon appears to be independent of the production of PAF and of cyclo‐oxygenase metabolites. By contrast, the production of the metabolites of the lipoxygenase pathway by platelets could account for the marked leucopenia observed following the immunological stimulation.

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“…3A). These reactions will generate chain-shortened metabolites, such as tetranor-12(R)-HETE [8(R)-HHxTrE], or -hydroxylated metabolites such as 12(R), 20-DiHETE, respectively (Marcus et al, 1984;Gordon et al, 1989). An additional metabolic pathway involving oxidation of 12-HETE to a keto intermediate (12-oxo-ETE) followed by keto-reduction to 12(R)-HETrE, a 12(S)HETE analog, has been described in porcine neutrophil and bovine corneal epithelial microsomes (Yamamoto et al, 1994).…”

Section: Metabolites Of 12(r)-hete Fail To Activate Ahrmentioning

confidence: 99%

12(R)-Hydroxy-5(Z),8(Z),10(E),14(Z)-eicosatetraenoic Acid [12(R)-HETE], an Arachidonic Acid Derivative, Is an Activator of the Aryl Hydrocarbon Receptor

Chiaro¹,

Patel²,

Perdew³

2008

Mol Pharmacol

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The aryl hydrocarbon receptor (AHR) is a ligand-regulated transcription factor that can be activated by structurally diverse chemicals, ranging from environmental carcinogens to dietary metabolites. Evidence supporting a necessary role for the AHR in normal biology has been established; however, identification of key endogenous ligand/activator remains to be established. Here, we report the ability of 12(R)-hydroxy-5(Z),8(Z),10(E), 14(Z)-eicosatetraenoic acid [12(R)-HETE], an arachidonic acid metabolite produced by either a lipoxygenase or cytochrome P-450 pathway, to act as a potent indirect modulator of the AHR pathway. In contrast, structurally similar HETE isomers failed to demonstrate significant activation of the AHR. Electrophoretic mobility shift assays, together with ligand competition binding experiments, have demonstrated the inability of 12(R)-HETE to directly bind or directly activate the AHR to a DNA binding species in vitro. However, cell-based xenobioticresponsive element-driven luciferase reporter assays indicate the ability of 12(R)-HETE to modulate AHR activity, and quantitation of induction of an AHR target gene confirmed 12(R)-HETE's ability to activate AHR-mediated transcription, even at high nanomolar concentrations in human hepatoma (HepG2)-and keratinocyte (HaCaT)-derived cell lines. One explanation for these results is that a metabolite of 12(R)-HETE is acting as a direct ligand for the AHR. However, several known metabolites failed to exhibit AHR activity. The ability of 12(R)-HETE to activate AHR target genes required receptor expression. These results indicate that 12(R)-HETE can serve as a potent activator of AHR activity and suggest that in normal and inflammatory disease conditions in skin, 12(R)-HETE is produced, perhaps leading to AHR activation.

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12S,20-dihydroxyicosatetraenoic acid: a new icosanoid synthesized by neutrophils from 12S-hydroxyicosatetraenoic acid produced by thrombin- or collagen-stimulated platelets.

Cited by 127 publications

References 11 publications

Thrombin‐activated platelets promote leukotriene B₄ synthesis in polymorphonuclear leucocytes stimulated by physiological agonists

Thrombin‐activated platelets promote leukotriene B₄ synthesis in polymorphonuclear leucocytes stimulated by physiological agonists

Antigen induces leucopenia in non‐immunised guinea‐pigs injected with platelets from actively sensitized animals

12(R)-Hydroxy-5(Z),8(Z),10(E),14(Z)-eicosatetraenoic Acid [12(R)-HETE], an Arachidonic Acid Derivative, Is an Activator of the Aryl Hydrocarbon Receptor

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12S,20-dihydroxyicosatetraenoic acid: a new icosanoid synthesized by neutrophils from 12S-hydroxyicosatetraenoic acid produced by thrombin- or collagen-stimulated platelets.

Cited by 127 publications

References 11 publications

Thrombin‐activated platelets promote leukotriene B4 synthesis in polymorphonuclear leucocytes stimulated by physiological agonists

Thrombin‐activated platelets promote leukotriene B4 synthesis in polymorphonuclear leucocytes stimulated by physiological agonists

Antigen induces leucopenia in non‐immunised guinea‐pigs injected with platelets from actively sensitized animals

12(R)-Hydroxy-5(Z),8(Z),10(E),14(Z)-eicosatetraenoic Acid [12(R)-HETE], an Arachidonic Acid Derivative, Is an Activator of the Aryl Hydrocarbon Receptor

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Thrombin‐activated platelets promote leukotriene B₄ synthesis in polymorphonuclear leucocytes stimulated by physiological agonists

Thrombin‐activated platelets promote leukotriene B₄ synthesis in polymorphonuclear leucocytes stimulated by physiological agonists