20-Hydroxy- and 20-carboxy-leukotriene (LT) B4 downregulate LTB4 -mediated responses of human neutrophils and eosinophils

J Leukoc Biol. 2019 Jun;105(6):1131-1142. doi: 10.1002/JLB.MA0718-306R. Epub 2019 Jan 24.


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.

Keywords: 5-oxo-ETE; eosinophils; host defense; leukotriene B4; lipoxin A4; neutrophils; resolvin E1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonic Acids / pharmacology
  • Benzopyrans / pharmacology
  • Carboxylic Acids / pharmacology
  • Eicosapentaenoic Acid / analogs & derivatives
  • Eicosapentaenoic Acid / pharmacology
  • Eosinophils / cytology
  • Eosinophils / immunology*
  • Humans
  • Leukotriene B4 / immunology*
  • Leukotriene B4 / pharmacology
  • Neutrophils / cytology
  • Neutrophils / immunology*
  • Receptors, Leukotriene B4 / antagonists & inhibitors
  • Receptors, Leukotriene B4 / immunology*


  • Arachidonic Acids
  • Benzopyrans
  • Carboxylic Acids
  • LTB4R protein, human
  • Receptors, Leukotriene B4
  • 5-oxo-6,8,11,14-eicosatetraenoic acid
  • Leukotriene B4
  • Eicosapentaenoic Acid
  • 5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid
  • CP 105696