Leukotriene B4 augments and restores FcγRs-dependent phagocytosis in macrophages

Fuyuki Okamoto, Kazuko Saeki, Hideki Sumimoto, Sho Yamasaki, Takehiko Yokomizo

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    49 Citations (Scopus)


    Phagocytosis by macrophages is essential for host defense, i.e. preventing invasion of pathogens and foreign materials. Macrophages engulf immunoglobulin G (IgG)-opsonized particles through the action of the receptors for the Fc of IgG (FcγRs). Leukotriene B4 (LTB4) is a classical lipid chemoattractant derived from arachidonic acid. Leukotriene B4 receptor 1 (BLT1), a high affinity LTB4 receptor, is expressed in a variety of immune cells such as neutrophils, macrophages, and dendritic cells. Although LTB4 has been shown to enhance macrophage phagocytosis, few studies have investigated the intracellular mechanisms involved in this in detail. Furthermore, there have been no reports of the direct cross-talk between LTB4-BLT1 and IgG-FcγRs signaling. Here, we show that FcγRs-dependent phagocytosis was attenuated in BLT1-deficient macrophages as compared with wild-type (WT) cells. Moreover, cross-talk between LTB 4-BLT1 and IgG-FcγRs signaling was identified at the level of phosphatidylinositol 3-OH kinase (PI3K) and Rac, downstream of Syk. In addition, the trimeric Gi protein (Gi) was found to be essential for BLT1-dependent phagocytosis. Surprisingly, we found that LTB 4-BLT1 signaling restores phagocytosis in the absence of FcγRs signaling. These data indicate that LTB4-BLT1 signaling plays a pivotal role in macrophage phagocytosis and innate immunity.

    Original languageEnglish
    Pages (from-to)41113-41121
    Number of pages9
    JournalJournal of Biological Chemistry
    Issue number52
    Publication statusPublished - Dec 24 2010

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Molecular Biology
    • Cell Biology


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