12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) is a 17-carbon hydroxy fatty acid that is biosynthesized either by enzymatic pathways, like thromboxane synthase (TXAS) and cytochrome P450 or a non-enzymatic pathway. TXAS catalyzes the isomerization reaction from PGH₂ to 12-HHT, malondialdehyde, and TXA₂ at a ratio of 1:1:1. Furthermore, 12-HHT has been considered as a mere byproduct of TXA₂ biosynthesis, and its biological function has long been uncertain. BLT2 was initially identified as a low-affinity leukotriene B₄ (LTB₄) receptor, which is also activated by various hydroxy-eicosatetraenoic acids (HETEs), suggesting that BLT2 may be activated by other endogenous ligands apart from LTB₄ and HETEs. By unbiased ligand screening using crude lipids from rat organs, 12-HHT has been identified as an endogenous agonist for BLT2. The 12-HHT–BLT2 axis induces mast cell migration and contributes to allergic inflammation. BLT2 is also expressed in epithelial cells of the small intestine and skin in mice and contributes to in vivo epithelial barrier functions.

12( S )-羟基十七-5Z,8E,10E-三烯酸 (12-HHT) 是一种 17 个碳羟基脂肪酸，可通过酶促途径（如血栓素合酶 (TXAS) 和细胞色素 P450）或非酶促途径生物合成。途径。 TXAS催化PGH ₂以1:1:1的比例异构化为12-HHT、丙二醛和TXA ₂ 。此外，12-HHT一直被认为仅仅是TXA ₂生物合成的副产物，其生物学功能长期以来一直不确定。 BLT2 最初被鉴定为低亲和力白三烯 B ₄ (LTB ₄ ) 受体，也被各种羟基二十碳四烯酸 (HETE) 激活，表明 BLT2 可能被除 LTB ₄和 HETE 之外的其他内源配体激活。通过使用大鼠器官的粗脂质进行无偏配体筛选，12-HHT 已被鉴定为 BLT2 的内源性激动剂。 12-HHT-BLT2 轴诱导肥大细胞迁移并导致过敏性炎症。 BLT2 也在小鼠小肠和皮肤的上皮细胞中表达，并有助于体内上皮屏障功能。