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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)B4on phagocytosis of B. burgdorferi. Bone marrow-derived macrophages (BMDMs) from 5-LOX−/−mice were defective in the uptake and killing of B. burgdorferifrom the earliest stages of spirochete internalization. BMDMs from mice deficient for the LTB4high-affinity receptor (BLT1−/−) were also unable to efficiently phagocytose B. burgdorferi. Addition 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.

Pneumonic plague, caused by Yersinia pestis, is a rapidly progressing bronchopneumonia involving focal bacterial growth, neutrophilic congestion, and alveolar necrosis. Within a short time after inhalation of Y. pestis, inflammatory cytokines are expressed via the Toll/interleukin-1 (IL-1) adaptor myeloid differentiation primary response 88 (MyD88), which facilitates the primary lung infection.

Yersinia pestiscauses bubonic, pneumonic, and septicemic plague. Although no longer responsible for pandemic outbreaks, pneumonic plague continues to be a challenge for medical treatment and has been classified as a reemerging disease in some parts of the world.