20-Hydroxy- and 20-carboxy-leukotriene (LT) B4 downregulate LTB4 -mediated responses of human neutrophils and eosinophils
©2019 Society for Leukocyte Biology..
Leukotriene B4 (LTB4 ) plays a prominent role in innate immunity as it induces phagocyte recruitment, the release of antimicrobial effectors, and as it potentiates the ingestion and killing of pathogens. In humans, LTB4 has a short half-life and is rapidly metabolized by leukocytes, notably into 20-OH- and 20-COOH-LTB4 by neutrophils. Although these LTB4 metabolites bind to the BLT1 receptor with high affinity, they activate neutrophils to a much lower extent than LTB4 . We thus postulated that LTB4 metabolites could dampen BLT1 -mediated responses, therefore limiting the impact of LTB4 on human neutrophil functions. We found that 20-OH-LTB4 and 20-COOH-LTB4 inhibited all of the LTB4 -mediated neutrophil responses we tested (migration, degranulation, leukotriene biosynthesis). The potencies of the different compounds at inhibiting LTB4 -mediated responses were 20-OH-LTB4 = CP 105,696 (BLT1 antagonist) > > 20-COOH-LTB4 ≥ resolvin E1 (RVE1 ). In contrast, the fMLP- and IL-8-mediated responses we tested were not affected by the LTB4 metabolites or RVE1 . 20-OH-LTB4 and 20-COOH-LTB4 also inhibited the LTB4 -mediated migration of human eosinophils but not that induced by 5-KETE. Moreover, using 20-COOH-LTB4 , LTB4 , and LTB4 -alkyne, we show that LTB4 is a chemotactic, rather than a chemokinetic factor for both human neutrophils and eosinophils. In conclusion, our data indicate that LTB4 metabolites and RVE1 act as natural inhibitors of LTB4 -mediated responses. Thus, preventing LTB4 ω-oxidation might result in increased innate immunity and granulocyte functions.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:105 |
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| Enthalten in: |
Journal of leukocyte biology - 105(2019), 6 vom: 14. Juni, Seite 1131-1142 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Archambault, Anne-Sophie [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.05.2020 Date Revised 05.05.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/JLB.MA0718-306R |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM293041202 |
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| 100 | 1 | |a Archambault, Anne-Sophie |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a 20-Hydroxy- and 20-carboxy-leukotriene (LT) B4 downregulate LTB4 -mediated responses of human neutrophils and eosinophils |
| 264 | 1 | |c 2019 | |
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| 500 | |a Date Revised 05.05.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a ©2019 Society for Leukocyte Biology. | ||
| 520 | |a Leukotriene B4 (LTB4 ) plays a prominent role in innate immunity as it induces phagocyte recruitment, the release of antimicrobial effectors, and as it potentiates the ingestion and killing of pathogens. In humans, LTB4 has a short half-life and is rapidly metabolized by leukocytes, notably into 20-OH- and 20-COOH-LTB4 by neutrophils. Although these LTB4 metabolites bind to the BLT1 receptor with high affinity, they activate neutrophils to a much lower extent than LTB4 . We thus postulated that LTB4 metabolites could dampen BLT1 -mediated responses, therefore limiting the impact of LTB4 on human neutrophil functions. We found that 20-OH-LTB4 and 20-COOH-LTB4 inhibited all of the LTB4 -mediated neutrophil responses we tested (migration, degranulation, leukotriene biosynthesis). The potencies of the different compounds at inhibiting LTB4 -mediated responses were 20-OH-LTB4 = CP 105,696 (BLT1 antagonist) > > 20-COOH-LTB4 ≥ resolvin E1 (RVE1 ). In contrast, the fMLP- and IL-8-mediated responses we tested were not affected by the LTB4 metabolites or RVE1 . 20-OH-LTB4 and 20-COOH-LTB4 also inhibited the LTB4 -mediated migration of human eosinophils but not that induced by 5-KETE. Moreover, using 20-COOH-LTB4 , LTB4 , and LTB4 -alkyne, we show that LTB4 is a chemotactic, rather than a chemokinetic factor for both human neutrophils and eosinophils. In conclusion, our data indicate that LTB4 metabolites and RVE1 act as natural inhibitors of LTB4 -mediated responses. Thus, preventing LTB4 ω-oxidation might result in increased innate immunity and granulocyte functions | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Poirier, Samuel |e verfasserin |4 aut | |
| 700 | 1 | |a Lefebvre, Julie-S |e verfasserin |4 aut | |
| 700 | 1 | |a Robichaud, Philippe-Pierre |e verfasserin |4 aut | |
| 700 | 1 | |a Larose, Marie-Chantal |e verfasserin |4 aut | |
| 700 | 1 | |a Turcotte, Caroline |e verfasserin |4 aut | |
| 700 | 1 | |a Martin, Cyril |e verfasserin |4 aut | |
| 700 | 1 | |a Provost, Véronique |e verfasserin |4 aut | |
| 700 | 1 | |a Boudreau, Luc H |e verfasserin |4 aut | |
| 700 | 1 | |a McDonald, Patrick P |e verfasserin |4 aut | |
| 700 | 1 | |a Laviolette, Michel |e verfasserin |4 aut | |
| 700 | 1 | |a Surette, Marc E |e verfasserin |4 aut | |
| 700 | 1 | |a Flamand, Nicolas |e verfasserin |4 aut | |
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