Leukotriene B4 Augments and Restores FcγRs‐dependent Phagocytosis in Macrophages

Phagocytosis by macrophages is essential for host defense: preventing invasion of pathogens and foreign materials. Macrophages engulf immunoglobulin G (IgG)‐opsonized particles through the action of the receptors for the Fc of IgG (FcγRs). Leukotriene B 4 (LTB 4 ) is a classical lipid chemoattractant derived from arachidonic acid. BLT1, a high‐affinity LTB 4 receptor, is expressed in a variety of immune cells such as neutrophils, macrophages and dendritic cells. Although LTB 4 has been shown to enhance macrophage phagocytosis, few studies have investigated the intracellular mechanisms involved in this in detail. Furthermore, there have been no reports of the direct crosstalk between LTB 4 ‐BLT1 and IgG‐FcγRs signaling. Here we show that FcγRs‐dependent phagocytosis was attenuated in BLT1‐deficient macrophages as compared to wild‐type (WT) cells. Moreover, crosstalk between LTB 4 ‐BLT1 and IgG‐FcγRs signaling was identified at the level of phosphatidylinositol 3‐OH kinase (PI3K) and Rac, downstream of Syk. In addition, the trimeric Gi protein (Gi) was found to be essential for BLT1‐dependent phagocytosis. Surprisingly, we found that LTB 4 ‐BLT1 signaling restores phagocytosis in the absence of FcγRs signaling. These data indicate that LTB 4 ‐BLT1 signaling plays a pivotal role in macrophage phagocytosis and innate immunity.