LTB4 is a potent pro-inflammatory eicosanoid lipid mediator derived from arachadonic acid via the 5-lipoxygenase pathways. LTB4 is believed to confer its effect or functions on leukocytes predominantly via BLTR1, its high affinity, and heptahelical transmembrane receptor, located predominantly on leukocytes. LTB4 was initially identified as a neutrophil chemo attractant, and has marked effects on neutrophil recruitment and migration, oxidative free radical formation, and even regulation of gene expression. Interestingly, however, though BLTR1 is robustly expressed on human monocyte, the role of LTB4 in monocyte biology is far less characterized. Thus, the goal of our proposal is to delineate the role of LTB4 in monocyte recruitment both in vitro and in vivo.
Our first aim will be to test whether LTB4 can trigger the adhesion of monocyte under physiologically relevant flow conditions in vitro.
Our second aim will be to test whether the absence of the LTB4 receptor BLTR1 modulates the formation of a monocyte-dependent disease process: atherosclerotic lesion development in a murine model. We will cross the BLTR1 receptor knockout with the proatherogenic ApoE knockout mouse to definitively evaluate the role of BLTR1 on leukocyte trafficking and atherogenesis.
