PMID- 28053185 OWN - NLM STAT- MEDLINE DCOM- 20170828 LR - 20210217 IS - 1539-7262 (Electronic) IS - 0022-2275 (Print) IS - 0022-2275 (Linking) VI - 58 IP - 3 DP - 2017 Mar TI - Macrophage LTB(4) drives efficient phagocytosis of Borrelia burgdorferi via BLT1 or BLT2. PG - 494-503 LID - 10.1194/jlr.M068882 [doi] AB - 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)B(4) 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 LTB(4) high-affinity receptor (BLT1(-/-)) were also unable to efficiently phagocytose B. burgdorferi Addition of exogenous LTB(4) augmented the phagocytic capability of BMDMs from both 5-LOX(-/-) and BLT1(-/-) mice, suggesting that the low-affinity LTB(4) receptor, BLT2, might be involved. Blocking BLT2 activity with the specific antagonist, LY255283, inhibited phagocytosis in LTB(4)-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 LTB(4) in mediating phagocytosis in murine macrophages. This study demonstrates that LTB(4) promotes macrophage phagocytosis of bacteria via BLT1, and that BLT2 can fulfill this role in the absence of BLT1. CI - Copyright (c) 2017 by the American Society for Biochemistry and Molecular Biology, Inc. FAU - Zhang, Yan AU - Zhang Y AD - Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO 65211. FAU - Olson, Rachel M AU - Olson RM AD - Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO 65211. FAU - Brown, Charles R AU - Brown CR AD - Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO 65211 brownchar@missouri.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170104 PL - United States TA - J Lipid Res JT - Journal of lipid research JID - 0376606 RN - 0 (Ltb4r1 protein, mouse) RN - 0 (Ltb4r2 protein, mouse) RN - 0 (Receptors, Leukotriene B4) RN - 0 (Tetrazoles) RN - 1HGW4DR56D (Leukotriene B4) RN - EC 1.13.11.34 (Arachidonate 5-Lipoxygenase) RN - H037W1I5AL (LY 255283) SB - IM MH - Animals MH - Arachidonate 5-Lipoxygenase/*genetics/metabolism MH - Borrelia burgdorferi/genetics/pathogenicity MH - Disease Models, Animal MH - Humans MH - Leukotriene B4/administration & dosage/genetics/metabolism MH - Lyme Disease/*genetics/metabolism/microbiology/pathology MH - Macrophages/metabolism/pathology MH - Mice MH - Mice, Transgenic MH - Phagocytosis/genetics MH - Receptors, Leukotriene B4/antagonists & inhibitors/*genetics MH - Tetrazoles/administration & dosage PMC - PMC5335579 OTO - NOTNLM OT - bacteria OT - bone marrow-derived macrophage OT - eicosanoids OT - immunology OT - leukotriene B4 OT - leukotriene B4 receptor 1 OT - leukotriene B4 receptor 2 OT - leukotrienes OT - phagocytosis OT - receptors EDAT- 2017/01/06 06:00 MHDA- 2017/08/29 06:00 PMCR- 2018/03/01 CRDT- 2017/01/06 06:00 PHST- 2016/04/28 00:00 [received] PHST- 2016/12/15 00:00 [revised] PHST- 2017/01/06 06:00 [pubmed] PHST- 2017/08/29 06:00 [medline] PHST- 2017/01/06 06:00 [entrez] PHST- 2018/03/01 00:00 [pmc-release] AID - S0022-2275(20)30443-0 [pii] AID - m068882 [pii] AID - 10.1194/jlr.M068882 [doi] PST - ppublish SO - J Lipid Res. 2017 Mar;58(3):494-503. doi: 10.1194/jlr.M068882. Epub 2017 Jan 4.