20-Hydroxy- and 20-carboxy-leukotriene (LT) B4 downregulate LTB4-mediated responses of human neutrophils and eosinophils
| Autor: | Michel Laviolette, Marie-Chantal Larose, Anne-Sophie Archambault, Cyril Martin, Caroline Turcotte, Samuel J. Poirier, Julie-S Lefebvre, Véronique Provost, Philippe-Pierre Robichaud, Nicolas Flamand, Patrick P. McDonald, Luc H. Boudreau, Marc E. Surette |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Phagocyte Leukotriene B4 Immunology Pharmacology Granulocyte Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Immunology and Allergy Receptor Leukotriene Innate immune system Degranulation hemic and immune systems Chemotaxis Cell Biology respiratory system biological factors respiratory tract diseases 3. Good health 030104 developmental biology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis lipids (amino acids peptides and proteins) |
| Zdroj: | Journal of Leukocyte Biology. 105:1131-1142 |
| ISSN: | 1938-3673 0741-5400 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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