Malissein Emilie, Reynaud Stéphane, Bordessoule Dominique, Faucher Jean Luc, Turlure Pascal, Trimoreau Franck, Denizot Yves
Laboratoire d'Homéostasie Cellulaire et Pathologie, Faculté de Médecine, Limoges, France.
Leuk Res. 2006 Oct;30(10):1309-13. doi: 10.1016/j.leukres.2005.12.017. Epub 2006 Feb 7.
The ability of prostaglandin E2 (PGE2) to regulate the immune system is well documented. PGE2 effects are mediated through interactions with four distinct membrane EP receptors (EP(1-4)). We investigated, for the first time, the functionality of EP receptors on immature forms of blast cells of acute myeloid leukemic (AML) and acute lymphoid leukemic (ALL) patients. RT-PCR experiments documented the presence of the four EP receptor subtype transcripts in leukemic blasts of AML M0, AML M1, AML M2 and ALL patients. Western blot analysis only documented the presence of the EP2 receptor. Functional assays (cAMP production, calcium flux) confirmed Western blot results, i.e., the presence of functional EP2 receptors. Results of the present study suggest that the mechanism used by PGE2 to influence blast physiology is mediated through the EP2 receptor subtype, and subsequently through a cAMP-elevating effect. Results obtained with M0-2 subtypes have to be necessarily extended to more differentiated phenotype.
前列腺素E2（PGE2）调节免疫系统的能力已有充分记载。PGE2的作用是通过与四种不同的膜EP受体（EP(1 - 4)）相互作用来介导的。我们首次研究了急性髓性白血病（AML）和急性淋巴细胞白血病（ALL）患者原始细胞未成熟形式上EP受体的功能。RT-PCR实验证明在AML M0、AML M1、AML M2和ALL患者的白血病原始细胞中存在四种EP受体亚型转录本。蛋白质印迹分析仅证明了EP2受体的存在。功能测定（cAMP产生、钙通量）证实了蛋白质印迹结果，即存在功能性EP2受体。本研究结果表明，PGE2影响原始细胞生理的机制是通过EP2受体亚型介导的，随后通过升高cAMP的作用。M0 - 2亚型获得的结果必然要扩展到更分化的表型。
