15-deoxy-Δ12,14-prostaglandins D2 and J2 are potent activators of human eosinophils
15-deoxy-Δ12,14-prostaglandins D2 and J2 are potent activators of human eosinophils
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DOI：
10.4049/jimmunol.168.7.3563
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发表时间：
2002-04-01
影响因子：
4.4
通讯作者：
Powell, WS
中科院分区：
文献类型：
--
作者：
Monneret, G;Li, HP;Powell, WS
15-脱氧-Delta(12，14)-PDJ(2)(15d-PGJ(2))是前列腺素D(2)的降解产物，PGD(2)具有多种抑制作用，其中一些作用是由过氧化物酶体增殖物激活受体-γ介导的。与已报道的对巨噬细胞和其他细胞的抑制作用相比，我们发现该化合物是一种有效的嗜酸性粒细胞激活剂，可诱导钙动员、肌动蛋白聚合和CD11b表达。它对嗜酸性粒细胞有选择性，对中性粒细胞或单核细胞几乎没有影响。15D-PGJ(2)的EC50接近10 nM，与其前体PGD2的EC50相似。因此，激活嗜酸性粒细胞所需的15d-PGJ(2)浓度远低于其抗炎作用所需的浓度(通常为微摩尔)。15-脱氧-Delta(12，14)-前列腺素D-2(15d-PGD(2))也是一种有效的嗜酸性粒细胞激活剂，其EC50与PGD2大致相同，而Delta(12)-PGJ(2)的作用略弱。经PGD2处理的嗜酸性粒细胞对15d-PGJ(2)不再有反应，反之亦然，但在这两种情况下，细胞仍对另一种二十烷类促炎介质5-氧代-6，8，11，14-二十碳四烯酸有反应。这表明15d-PGJ2的作用是由最近在嗜酸性粒细胞中发现的表达在Th-2细胞上的DP2/趋化受体同源分子介导的。15D-PGJ2对DP2受体具有选择性，对DP1受体介导的血小板腺苷环化酶活性无影响。我们的结论是，15d-PGJ(2)和15d-PGD(2)是选择性的DP2受体激动剂，其激活人嗜酸性粒细胞的效力至少是15d-PGJ2对其他细胞抗炎作用的100倍。
15-Deoxy-Delta(12,14)-PDJ(2) (15d-PGJ(2)) is a degradation product of PGD(2) that has been proposed as an anti-inflammatory compound because of its various inhibitory effects, some of which are mediated by peroxisome proliferator-activated receptor-gamma. In contrast to its reported inhibitory effects on macrophages and other cells, we found that this compound is a potent activator of eosinophils, inducing calcium mobilization, actin polymerization, and CD11b expression. It is selective for eosinophils, having little or no effect on neutrophils or monocytes. 15d-PGJ(2) has an EC50 of similar to10 nM, similar to that of its precursor, PGD2. The concentrations of 15d-PGJ(2) required to activate eosinophils are thus much lower than those required for its anti-inflammatory effects (usually micromolar). 15-Deoxy-Delta(12,14)-prostagiandin D-2 (15d-PGD(2)) is also a potent activator of eosinophils, with an EC50 about the same as that of PGD2, whereas Delta(12)-PGJ(2), is slightly less potent. Eosinophils pretreated with PGD2 no longer respond to 15d-PGJ(2), and vice versa, but in both cases the cells still respond to another eicosanoid proinflammatory mediator, 5-oxo-6,8,11,14-eicosatetraenoic acid. This indicates that the effects of 15d-PGJ2 are mediated by the DP2/chemoattractant receptor-homologous molecule expressed on Th-2 cells that has recently been identified in eosinophils. 15d-PGJ2 is selective for the DP2 receptor, in that it has no effect on DP1 receptor-mediated adenylyl cyclase activity in platelets. We conclude that 15d-PGJ(2) and 15d-PGD(2) are selective DP2 receptor agonists that activate human eosinophils with potencies at least 100 times greater than those for the proposed anti-inflammatory effects of 15d-PGJ2 on other cells.