| First Author | Okuno T | Year | 2008 |
| Journal | J Exp Med | Volume | 205 |
| Issue | 4 | Pages | 759-66 |
| PubMed ID | 18378794 | Mgi Jnum | J:133998 |
| Mgi Id | MGI:3784755 | Doi | 10.1084/jem.20072329 |
| Citation | Okuno T, et al. (2008) 12(S)-Hydroxyheptadeca-5Z, 8E, 10E-trienoic acid is a natural ligand for leukotriene B4 receptor 2. J Exp Med 205(4):759-66 |
| abstractText | Activated blood platelets and macrophages metabolize prostaglandin H(2) into thromboxane A(2) and 12(S)-hydroxyheptadeca-5Z, 8E, 10E-trienoic acid (12-HHT) in an equimolar ratio through the action of thromboxane synthase. Although it has been shown that 12-HHT is abundant in tissues and bodily fluids, this compound has long been viewed as a by-product lacking any specific function. We show that 12-HHT is a natural ligand for leukotriene B(4) (LTB(4)) receptor-2 (BLT2), a G protein-coupled receptor that was originally identified as a low-affinity receptor for LTB(4). BLT2 agonistic activity in lipid fractions from rat small intestine was identified as 12-HHT using high-performance liquid chromatography and mass spectrometry. Exogenously expressed BLT2 in mammalian cells was activated by synthetic 12-HHT, as assessed by guanosine 5'-O-(3-thio) triphosphate binding, the activation of intracellular signaling pathways, and chemotaxis assay. Displacement analysis using [(3)H]LTB(4) showed that 12-HHT binds to BLT2 with a higher affinity than LTB(4). Lipid extracts from cyclooxygenase 1-deficient mice failed to activate BLT2. Bone marrow-derived mast cells (BMMCs) isolated from wild-type mice migrated toward a low concentration of 12-HHT, whereas BMMCs from BLT2-deficient mice did not. We conclude that 12-HHT is a natural lipid agonist of BLT2 in vivo and induces chemotaxis of mast cells. |
