Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DIP receptor
Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DIP receptor
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DOI：
10.1182/blood.v98.6.1942
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发表时间：
2001-09-15
期刊：
影响因子：
20.3
通讯作者：
Powell, WS
中科院分区：
文献类型：
--
作者：
Monneret, G;Gravel, S;Powell, WS
前列腺素D-2(PGD(2))是在哮喘患者暴露于变应原后释放的，通过前列腺素D(2)的腺酰环化酶偶联受体(DID受体)起作用。在这项研究中，据报道，人类嗜酸性粒细胞具有这种受体，有望抑制其激活。相反，研究发现前列腺素D-2是嗜酸性粒细胞趋化、肌动蛋白聚合、CD11b表达和L-选择素脱落的有力刺激因素。这些反应是嗜酸性粒细胞特有的，因为中性粒细胞对前列腺素D-2的反应很少或没有反应，这不是由于与其他前列腺素受体的相互作用，因为前列腺素E-2和F-2α、U46619(血栓素A(2)类似物)和卡巴前列环素(前列环素类似物)显示很少或没有活性。此外，选择性DID受体激动剂BW245C和选择性DID受体拮抗剂BWA868C都不能阻止它们的存在，表明它们不是由DID受体介导的。前列腺素D2代谢产物13，14-二氢-15-氧代前列腺素D-2可诱导嗜酸性粒细胞活化，但不能刺激DID受体介导的环磷酸腺苷(CAMP)的形成。这些结果表明，除了经典的抑制性DID受体外，嗜酸性粒细胞还拥有第二个新的DP2受体，该受体与PGD(2)诱导的细胞激活有关。这两种受体似乎相互作用，调节嗜酸性粒细胞对PGD(2)的反应，因为BWA868C阻断DPI受体介导的cAMP产生导致DP2受体介导的CD11b表达增强。DPI和DP2受体之间的平衡可以决定前列腺素D-2激活嗜酸性粒细胞的程度，并可能在哮喘的嗜酸性粒细胞募集中发挥作用。
Prostaglandin D-2 (PGD(2)) is released following exposure of asthmatics to allergen and acts via the adenylyl cyclase-coupled receptor for PGD(2) (DID receptor). In this study, it is reported that human eosinophils possess this receptor, which would be expected to inhibit their activation. In contrast, it was found that prostaglandin D-2 is a potent stimulator of eosinophil chemotaxis, actin polymerization, CD11b expression, and L-selectin shedding. These responses are specific for eosinophils, as neutrophils display little or no response to prostaglandin D-2 They were not due to interaction with receptors for other prostanoids, as prostaglandins E-2 and F-2 alpha, U46619 (a thromboxane A(2) analogue), and carbaprostacyclin (a prostacyclin analogue) displayed little or no activity. Furthermore, they were not shared by the selective DID receptor agonist BW245C and were not prevented by the selective DID receptor antagonist BWA868C, indicating that they were not mediated by DID receptors. In contrast, the prostaglandin D2 metabolite 13,14-dihydro-15-oxoprostaglandin D-2 induced eosinophil activation but did not stimulate DID receptor-mediated adenosine 3 ' ,5 ' -cyclic monophosphate (cAMP) formation. These results indicate that in addition to the classic inhibitory DID, receptor, eosinophils possess a second, novel DP2 receptor that is associated with PGD(2)-induced cell activation. These 2 receptors appear to interact to regulate eosinophil responses to PGD(2), as blockade of DPI receptor-mediated cAMP production by BWA868C resulted in enhanced DP2 receptor-mediated stimulation of CD11b expression. The balance between DPI and DP2 receptors could determine the degree to which prostaglandin D-2 can activate eosinophils and may play a role in eosinophil recruitment in asthma.