Tager Andrew M, Luster Andrew D
Division of Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Building 149-8301, 13th Street, Charlestown, MA 02129, USA.
Prostaglandins Leukot Essent Fatty Acids. 2003 Aug-Sep;69(2-3):123-34. doi: 10.1016/s0952-3278(03)00073-5.
Two receptors for leukotriene B(4) (LTB(4)) have been molecularly identified: BLT1 and BLT2. Both receptors are G protein-coupled seven transmembrane domain receptors, whose genes are located in very close proximity to each other in the human and mouse genomes. The two receptors differ in their affinity and specificity for LTB(4): BLT1 is a high-affinity receptor specific for LTB(4), whereas BLT2 is a low-affinity receptor that also binds other eicosanoids. The two receptors also differ in their pattern of expression with BLT1 being expressed primarily in leukocytes, whereas BLT2 is expressed more ubiquitously. By mediating the activities of LTB(4), these receptors participate both in host immune responses and in the pathogenesis of inflammatory diseases. Reduced disease severity in animal inflammatory models seen with LTB(4) receptor antagonists and in mice with targeted deletion of BLT1 have revealed important roles for LTB(4) and its receptors in regulating pathologic inflammation.
白三烯B4(LTB4)的两种受体已在分子水平上得到鉴定:BLT1和BLT2。这两种受体都是G蛋白偶联的七跨膜结构域受体,其基因在人类和小鼠基因组中彼此非常靠近。这两种受体对LTB4的亲和力和特异性不同:BLT1是对LTB4特异的高亲和力受体,而BLT2是也结合其他类二十烷酸的低亲和力受体。这两种受体的表达模式也不同,BLT1主要在白细胞中表达,而BLT2的表达更为广泛。通过介导LTB4的活性,这些受体既参与宿主免疫反应,也参与炎症性疾病的发病机制。在动物炎症模型中,使用LTB4受体拮抗剂以及BLT1基因敲除小鼠观察到疾病严重程度降低,这揭示了LTB4及其受体在调节病理性炎症中的重要作用。