文章基本信息

标题：Macrophage LTB4 drives efficient phagocytosis of Borrelia burgdorferi via BLT1 or BLT2
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作者：Yan Zhang ; Rachel M. Olson ; Charles R. Brown 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2017
卷号：58
期号：3
页码：494-503
DOI：10.1194/jlr.M068882
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：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.
关键词：eicosanoids ; immunology ; leukotrienes ; receptors ; phagocytosis ; bacteria ; leukotriene B₄ ; bone marrow-derived macrophage ; leukotriene B4 receptor 1 ; leukotriene B4 receptor 2