Schratl Petra, Sturm Eva M, Royer Julia F, Sturm Gunter J, Lippe Irmgard T, Peskar Bernhard A, Heinemann Akos
Institute of Experimental and Clinical Pharmacology, Medical University Graz, Graz, Austria.
Eur J Immunol. 2006 Sep;36(9):2401-9. doi: 10.1002/eji.200535672.
Several chemoattractants can regulate the recruitment of eosinophils to sites of inflammation, but the hierarchy among them is unknown. We observed here that eosinophil chemotaxis towards eotaxin or 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) was amplified up to sixfold in the presence of prostaglandin (PG) D2. This effect was only seen in eosinophils, and not in neutrophils or basophils. Pretreatment with the chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) antagonist ramatroban prevented the PGD2 enhancement of eosinophil migrations. In contrast, eotaxin or 5-oxo-ETE inhibited the migration of eosinophils towards PGD2. 5-oxo-ETE enhanced the chemotaxis to eotaxin, while eotaxin had no effect on 5-oxo-ETE-induced migration. 5-oxo-ETE induced the phosphorylation of p38 mitogen-activated protein kinase, and inhibition of p38 mitogen-activated protein kinase by SB-202190 converted the effect of 5-oxo-ETE on the chemotaxis to PGD2 from inhibition to enhancement. The presence of blood or plasma markedly decreased the sensitivity of eosinophils to eotaxin or 5-oxo-ETE, while responses to PGD2 were unaltered. In conclusion, PGD2 might be an initial chemoattractant, since it maintains its potency in the circulation and augments the responsiveness of eosinophils to other chemoattractants. In contrast, eotaxin seems to be an end-point chemoattractant, since it has reduced efficacy in blood and is capable of down-modulating eosinophil responsiveness to other chemoattractants.
几种趋化因子可调节嗜酸性粒细胞向炎症部位的募集，但它们之间的主次关系尚不清楚。我们在此观察到，在前列腺素（PG）D2存在的情况下，嗜酸性粒细胞对嗜酸性粒细胞趋化因子或5-氧代-6,8,11,14-二十碳四烯酸（5-氧代-ETE）的趋化作用增强了多达六倍。这种效应仅在嗜酸性粒细胞中出现，在中性粒细胞或嗜碱性粒细胞中未观察到。用TH2细胞上表达的趋化因子受体同源分子（CRTH2）拮抗剂雷马曲班预处理可阻止PGD2增强嗜酸性粒细胞的迁移。相反，嗜酸性粒细胞趋化因子或5-氧代-ETE可抑制嗜酸性粒细胞向PGD2的迁移。5-氧代-ETE增强了对嗜酸性粒细胞趋化因子的趋化作用，而嗜酸性粒细胞趋化因子对5-氧代-ETE诱导的迁移没有影响。5-氧代-ETE诱导p38丝裂原活化蛋白激酶的磷酸化，用SB-202190抑制p38丝裂原活化蛋白激酶可将5-氧代-ETE对向PGD2趋化作用的影响从抑制转变为增强。血液或血浆的存在显著降低了嗜酸性粒细胞对嗜酸性粒细胞趋化因子或5-氧代-ETE的敏感性，而对PGD2的反应未改变。总之，PGD2可能是一种初始趋化因子，因为它在循环中保持其效力并增强嗜酸性粒细胞对其他趋化因子的反应性。相反，嗜酸性粒细胞趋化因子似乎是一种终点趋化因子，因为它在血液中的效力降低，并且能够下调嗜酸性粒细胞对其他趋化因子的反应性。
