20-Hydroxy- and 20-carboxy-leukotriene (LT) B downregulate LTB -mediated responses of human neutrophils and eosinophils.

Title20-Hydroxy- and 20-carboxy-leukotriene (LT) B downregulate LTB -mediated responses of human neutrophils and eosinophils.
Publication TypeJournal Article
Year of Publication2019
AuthorsArchambault, A-S, Poirier, S, Lefebvre, J-S, Robichaud, P-P, Larose, M-C, Turcotte, C, Martin, C, Provost, V, Boudreau, LH, McDonald, PP, Laviolette, M, Surette, ME, Flamand, N
JournalJ Leukoc Biol
Date Published2019 Jun

Leukotriene B (LTB ) 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 has a short half-life and is rapidly metabolized by leukocytes, notably into 20-OH- and 20-COOH-LTB by neutrophils. Although these LTB metabolites bind to the BLT receptor with high affinity, they activate neutrophils to a much lower extent than LTB . We thus postulated that LTB metabolites could dampen BLT -mediated responses, therefore limiting the impact of LTB on human neutrophil functions. We found that 20-OH-LTB and 20-COOH-LTB inhibited all of the LTB -mediated neutrophil responses we tested (migration, degranulation, leukotriene biosynthesis). The potencies of the different compounds at inhibiting LTB -mediated responses were 20-OH-LTB  = CP 105,696 (BLT antagonist) > > 20-COOH-LTB ≥ resolvin E (RVE ). In contrast, the fMLP- and IL-8-mediated responses we tested were not affected by the LTB metabolites or RVE . 20-OH-LTB and 20-COOH-LTB also inhibited the LTB -mediated migration of human eosinophils but not that induced by 5-KETE. Moreover, using 20-COOH-LTB , LTB , and LTB -alkyne, we show that LTB is a chemotactic, rather than a chemokinetic factor for both human neutrophils and eosinophils. In conclusion, our data indicate that LTB metabolites and RVE act as natural inhibitors of LTB -mediated responses. Thus, preventing LTB ω-oxidation might result in increased innate immunity and granulocyte functions.

Alternate JournalJ. Leukoc. Biol.
PubMed ID30676680
Grant List / / Natural Sciences and Engineering Research Council of Canada /
/ / JD-Bégin-CRIUCPQ Foundation /
/ / Merck Merck Sharpe & Dohme - Université Laval /