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J Lipid Res. 2017 Mar;58(3):494-503. doi: 10.1194/jlr.M068882. Epub 2017 Jan 4.

Macrophage LTB4 drives efficient phagocytosis of Borrelia burgdorferi via BLT1 or BLT2.

Author information

1
Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO 65211.
2
Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO 65211 brownchar@missouri.edu.

Abstract

Unresolved experimental Lyme arthritis in C3H 5-lipoxygenase (5-LOX)-/- mice is associated with impaired macrophage phagocytosis of Borrelia burgdorferi In the present study, we further investigated the effects of the 5-LOX metabolite, leukotriene (LT)B4 on phagocytosis of B. burgdorferi Bone marrow-derived macrophages (BMDMs) from 5-LOX-/- mice were defective in the uptake and killing of B. burgdorferi from the earliest stages of spirochete internalization. BMDMs from mice deficient for the LTB4 high-affinity receptor (BLT1-/-) were also unable to efficiently phagocytose B. burgdorferi Addition of exogenous LTB4 augmented the phagocytic capability of BMDMs from both 5-LOX-/- and BLT1-/- mice, suggesting that the low-affinity LTB4 receptor, BLT2, might be involved. Blocking BLT2 activity with the specific antagonist, LY255283, inhibited phagocytosis in LTB4-stimulated BLT1-/- BMDMs, demonstrating a role for BLT2. However, the lack of a phagocytic defect in BLT2-/- BMDMs suggested that this was a compensatory effect. In contrast, 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid, a natural BLT2-specific high-affinity ligand, and resolvin E1, a BLT1 agonist, were both unable to boost phagocytosis in BMDMs from either 5-LOX-/- or BLT1-/- mice, suggesting a specific role for LTB4 in mediating phagocytosis in murine macrophages. This study demonstrates that LTB4 promotes macrophage phagocytosis of bacteria via BLT1, and that BLT2 can fulfill this role in the absence of BLT1.

KEYWORDS:

bacteria; bone marrow-derived macrophage; eicosanoids; immunology; leukotriene B4; leukotriene B4 receptor 1; leukotriene B4 receptor 2; leukotrienes; phagocytosis; receptors

PMID:
28053185
PMCID:
PMC5335579
DOI:
10.1194/jlr.M068882
[Indexed for MEDLINE]
Free PMC Article

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