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20‐Hydroxy‐ and 20‐carboxy‐leukotriene (LT) B 4 downregulate LTB 4 ‐mediated responses of human neutrophils and eosinophils
Author(s) -
Archambault AnneSophie,
Poirier Samuel,
Lefebvre JulieS,
Robichaud PhilippePierre,
Larose MarieChantal,
Turcotte Caroline,
Martin Cyril,
Provost Véronique,
Boudreau Luc H.,
McDonald Patrick P.,
Laviolette Michel,
Surette Marc E.,
Flamand Nicolas
Publication year - 2019
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.ma0718-306r
Subject(s) - leukotriene b4 , biology , leukotriene , downregulation and upregulation , immunology , neutrophile , microbiology and biotechnology , inflammation , biochemistry , asthma , gene
Leukotriene B 4 (LTB 4 ) 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, LTB 4 has a short half‐life and is rapidly metabolized by leukocytes, notably into 20‐OH‐ and 20‐COOH‐LTB 4 by neutrophils. Although these LTB 4 metabolites bind to the BLT 1 receptor with high affinity, they activate neutrophils to a much lower extent than LTB 4 . We thus postulated that LTB 4 metabolites could dampen BLT 1 ‐mediated responses, therefore limiting the impact of LTB 4 on human neutrophil functions. We found that 20‐OH‐LTB 4 and 20‐COOH‐LTB 4 inhibited all of the LTB 4 ‐mediated neutrophil responses we tested (migration, degranulation, leukotriene biosynthesis). The potencies of the different compounds at inhibiting LTB 4 ‐mediated responses were 20‐OH‐LTB 4 = CP 105,696 (BLT 1 antagonist) > > 20‐COOH‐LTB 4 ≥ resolvin E 1 (RVE 1 ). In contrast, the fMLP‐ and IL‐8‐mediated responses we tested were not affected by the LTB 4 metabolites or RVE 1 . 20‐OH‐LTB 4 and 20‐COOH‐LTB 4 also inhibited the LTB 4 ‐mediated migration of human eosinophils but not that induced by 5‐KETE. Moreover, using 20‐COOH‐LTB 4 , LTB 4 , and LTB 4 ‐alkyne, we show that LTB 4 is a chemotactic, rather than a chemokinetic factor for both human neutrophils and eosinophils. In conclusion, our data indicate that LTB 4 metabolites and RVE 1 act as natural inhibitors of LTB 4 ‐mediated responses. Thus, preventing LTB 4 ω‐oxidation might result in increased innate immunity and granulocyte functions.