Leukotriene B4 augments and restores FcγRs-dependent phagocytosis in macrophages

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

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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
Volume285
Issue number52
DOIs
Publication statusPublished - Dec 24 2010

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Leukotriene B4
Macrophages
Phagocytosis
Leukotriene B4 Receptors
Immunoglobulin G
Immunoglobulin Fc Fragments
Chemotactic Factors
Pathogens
Phosphatidylinositol 3-Kinases
Innate Immunity
Arachidonic Acid
Dendritic Cells
Neutrophils
Lipids
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Leukotriene B4 augments and restores FcγRs-dependent phagocytosis in macrophages. / Okamoto, Fuyuki; Saeki, Kazuko; Sumimoto, Hideki; Yamasaki, Shou; Yokomizo, Takehiko.

In: Journal of Biological Chemistry, Vol. 285, No. 52, 24.12.2010, p. 41113-41121.

Research output: Contribution to journalArticle

Okamoto, Fuyuki ; Saeki, Kazuko ; Sumimoto, Hideki ; Yamasaki, Shou ; Yokomizo, Takehiko. / Leukotriene B4 augments and restores FcγRs-dependent phagocytosis in macrophages. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 52. pp. 41113-41121.
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