Macrophage LTB drives efficient phagocytosis of via BLT1 or BLT2.

Unresolved experimental Lyme arthritis in C3H 5-lipoxygenase (5-LOX) mice is associated with impaired macrophage phagocytosis of In the present study, we further investigated the effects of the 5-LOX metabolite, leukotriene (LT)B on phagocytosis of Bone marrow-derived macrophages (BMDMs) from 5-LOX mice were defective in the uptake and killing of from the earliest stages of spirochete internalization. BMDMs from mice deficient for the LTB high-affinity receptor (BLT1) were also unable to efficiently phagocytose Addition of exogenous LTB augmented the phagocytic capability of BMDMs from both 5-LOX and BLT1 mice, suggesting that the low-affinity LTB receptor, BLT2, might be involved. Blocking BLT2 activity with the specific antagonist, LY255283, inhibited phagocytosis in LTB-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 in mediating phagocytosis in murine macrophages. This study demonstrates that LTB promotes macrophage phagocytosis of bacteria via BLT1, and that BLT2 can fulfill this role in the absence of BLT1.