Leukotrienes (LTs) are a class of mediators derived from arachidonic acid by the initiating activity of 5-lipoxygenase and 5-lipoxygenase–activating protein (FLAP). They are involved in self-defense systems against foreign bodies or microorganisms, but overproduction causes a variety of immune and inflammatory diseases. Two G protein–coupled receptors (GPCRs) have been cloned as receptors for leukotriene B4 (LTB4). The first, BLT1, known as a high-affinity LTB4 receptor, is expressed in various subsets of leukocytes and is responsible for LTB4-dependent leukocyte migration. The second, BLT2, was originally reported as a low-affinity LTB4 receptor and is now considered as a receptor for various oxidized fatty acids, including 12-hydroxyheptadecatrienoic acid (12-HHT) and hydroxyeicosatetraenoic acids (HETEs). BLT2 is expressed in epidermal keratinocytes and epithelial cells of intestine, cornea, and lung and is responsible for wound healing and epidermal barrier function. 
Human BLT1 consists of 352 amino acids and is mainly expressed in various subsets of leukocytes, including granulocytes, eosinophils, and effector-type CD4+ and CD8+ T cells, as well as certain subsets of dendritic cells and macrophages. BLT1 stimulation in leukocytes leads to degranulation through the production of phosphatidylinositol tris-phosphates (IP3) via activation of phosphatidylinositol-3-kinase (PI3 kinase). LTB4 also activates phagocytosis in macrophages through the activation of Gi, PI3 kinase, Rac, and Syk. Recently, the receptor for advanced glycation end products (RAGE) was identified as a BLT1-binding protein that regulates BLT1 signaling. RAGE functions as a molecular switch for BLT1, inhibits BLT1-dependent NF-κB activation, and stimulates BLT1-dependent chemotaxis. RAGE was also shown to bind to GPCRs other than BLT1 and is a new class of GPCR modulator and a new target of GPCR study. Five CysLT receptors have been identified: CysLT1, CysLT2, P2Y12, GPR99, and GPR17. CysLT1 is expressed in a variety of inflammatory cells, i.e., neutrophils, mast cells, and monocytes/macrophages, activation of CysLT1 by LTD4 results in the production of several second intracellular messengers through phospholipase Cβ.CysLT2 negatively regulates the development of Th2 pulmonary inflammation by inhibiting the CysLT1 functions on dendritic cells.

References

1.Yokomizo T,et al. J Clin Invest. 2018;128(7):2691–2701.