Leukotriene B4 Receptor Antagonism Reduces Monocytic Foam Cells in Mice

Leukotriene B4 (LTB4) is a potent chemotactic agent that activates monocytes through the LTB4 receptor (BLTR). We tested the hypothesis that LTB4 receptor blockade would slow atherosclerotic progression by inhibiting monocyte recruitment. Homozygous low-density receptor knockout (LDLr−/−) mice and apolipoprotein E deficient (apoE−/−) mice were treated with a specific LTB4 receptor antagonist, CP-105,696, for 35 days. In apoE−/−mice, treatment with the LTB4 antagonist did not affect plasma lipid concentrations but significantly reduced CD11b levels both in vascular lesions and whole blood. Compared with age-matched controls, lipid accumulation and monocyte infiltration were significantly reduced in treated apoE−/− mice at all time points tested. Lesion area reduction was also demonstrated in LDLr−/− mice maintained on a high-fat diet. LTB4 antagonism had no significant effect on lesion size in mice possessing the null alleles for another chemotactic agent, monocyte chemoattractant protein-1 (MCP-1−/−×apoE−...