title: Macrophage LTB4drives efficient phagocytosis ofBorrelia burgdorferivia BLT1 or BLT2.
abstract: Unresolved experimental Lyme arthritis in C3H 5-lipoxygenase (5-LOX)-/-mice is associated with impaired macrophage phagocytosis ofBorrelia burgdorferiIn the present study, we further investigated the effects of the 5-LOX metabolite, leukotriene (LT)B4on phagocytosis ofB. burgdorferiBone marrow-derived macrophages (BMDMs) from 5-LOX-/-mice were defective in the uptake and killing ofB. burgdorferifrom the earliest stages of spirochete internalization. BMDMs from mice deficient for the LTB4high-affinity receptor (BLT1-/-) were also unable to efficiently phagocytoseB. burgdorferiAddition of exogenous LTB4augmented the phagocytic capability of BMDMs from both 5-LOX-/-and BLT1-/-mice, suggesting that the low-affinity LTB4receptor, 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 LTB4in mediating phagocytosis in murine macrophages. This study demonstrates that LTB4promotes macrophage phagocytosis of bacteria via BLT1, and that BLT2 can fulfill this role in the absence of BLT1.
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO 65211.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO 65211.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Olson
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO 65211 brownchar@missouri.edu.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Brown
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics* / Q000378:metabolism; D025065:Borrelia burgdorferi / Q000235:genetics / Q000472:pathogenicity; D004195:Disease Models, Animal; D006801:Humans; D007975:Leukotriene B4 / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D008193:Lyme Disease / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D010587:Phagocytosis / Q000235:genetics; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors / Q000235:genetics*; D013777:Tetrazoles / Q000008:administration & dosage
chemical_list: C503704:Ltb4r1 protein, mouse; C412867:Ltb4r2 protein, mouse; D018102:Receptors, Leukotriene B4; D013777:Tetrazoles; D007975:Leukotriene B4; D001094:Arachidonate 5-Lipoxygenase; C063823:LY 255283
keywords: bacteria; bone marrow-derived macrophage; eicosanoids; immunology; leukotriene B4; leukotriene B4 receptor 1; leukotriene B4 receptor 2; leukotrienes; phagocytosis; receptors