Identification, signaling, and functions of LTB 4 receptors

Leukotriene B4 (LTB4), a lipid mediator produced from arachidonic acid, is a chemoattractant for inflammatory leukocytes. We identified two receptors for LTB4, the high-affinity receptor BLT1 and the low-affinity receptor BLT2. BLT1 is expressed in various subsets of leukocytes, and analyses of BLT1-deficient mice revealed that the LTB4/BLT1 axis enhances leukocyte recruitment to infected sites, and is involved in the elimination of pathogens. Hyperactivation of the LTB4/BLT1 axis induces acute and chronic inflammation, resulting in various inflammatory diseases. BLT2 was originally identified as a low-affinity receptor for LTB4, and we later identified 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (12-HHT) as a high-affinity ligand for BLT2. BLT2 is highly expressed in epithelial cells in various tissues including intestine and skin. Large quantities of 12-HHT are produced by activated platelets during skin injury, and activation of BLT2 on epidermal keratinocytes accelerates skin wound healing by enhancing cell migration. BLT2 signaling also enhances cell–cell junctions, protectes against transepidermal water loss, and preventes entry of environmental substances into the body.