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

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.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC5335579 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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

Zhang Yan Y Olson Rachel M RM Brown Charles R CR

Journal of lipid research 20170104 3

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 ...[more]

PMID: 28053185

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Project description:Low-dose alcohol possesses multiple bioactivities. Accordingly, we investigated the protective effect and related molecular mechanism of low-dose alcohol against acute stress- (AS-) induced renal injury. Herein, exhaustive swimming for 15 min combined with restraint stress for 3 h was performed to establish a rat acute stress model, which was verified by an open field test. Evaluation of renal function (blood creatinine and urea nitrogen), urine test (urine leukocyte esterase and urine occult blood), renal histopathology, oxidative stress, inflammation, and apoptosis was performed. The key indicators of the cytochrome P450 (CYP) 4A1/20-hydroxystilbenetetraenoic acid (20-HETE) pathway, cyclooxygenase (COX)/prostaglandin E2 (PGE2) pathway, and leukotriene B4 (LTB4)/leukotriene B4 receptor 1 (BLT1) pathway were measured by real-time PCR and ELISA. We found that low-dose alcohol (0.05 g/kg, i.p.) ameliorated AS-induced renal dysfunction and histological damage. Low-dose alcohol also attenuated AS-induced oxidative stress and inflammation, presenting as reduced malondialdehyde and hydrogen peroxide formation, increased superoxide dismutase and glutathione activity, and decreased myeloperoxidase, interleukin-6, interleukin-1β, and monocyte chemoattractant protein-1 levels (P < 0.05). Moreover, low-dose alcohol alleviated AS-induced apoptosis by downregulating Bax and cleaved caspase 3 protein expression and reduced numbers of terminal deoxynucleotidyl transferase-mediated dUTP nick-end label-positive cells (P < 0.01). Correlation analysis indicated that 20-HETE was strongly correlated with oxidative stress, while LTB4 was strongly correlated with inflammation. Low-dose alcohol inhibited AS-induced increases in CYP4A1, CYP4A2, CYP4A3, CYP4A8, and BLT1 mRNA levels and LTB4 and 20-HETE content (P < 0.01). Interestingly, low-dose alcohol had no effect on COX1 or COX2 mRNA expression or the concentration of PGE2. Furthermore, low-dose alcohol reduced calcium-independent phospholipase A2 mRNA expression, but did not affect secreted phospholipase A2 or cytosolic phospholipase A2 mRNA expression. Together, these results indicate that low-dose alcohol ameliorated AS-induced renal injury by inhibiting CYP4A/20-HETE and LTB4/BLT1 pathways, but not the COX/PGE2 pathway.

Dataset Information

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

Publications

Macrophage LTB<sub>4</sub> drives efficient phagocytosis of <i>Borrelia burgdorferi</i> via BLT1 or BLT2.

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