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Serotonin Uptake Is LargelyMediated by Plateletsversus Lymphocytes in Peripheral Blood Cells

机译:血清素的摄入量很大由血小板介导与外周血细胞中的淋巴细胞

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摘要

The serotonin transporter (SERT), a primary target for many antidepressants, is expressed in the brain and also in peripheral blood cells. Although platelet SERT function is well accepted, lymphocyte SERT function has not been definitively characterized. Due to their small size, platelets often are found in peripheral blood mononuclear cell preparations aimed at isolating lymphocytes, monocytes, and macrophages. The presence of different cells makes it difficult to assign SERT expression and function to specific cell types. Here, we use flow cytometry and IDT307, a monoamine transporter substrate that fluoresces after uptake into cells, to investigate SERT function in lymphocyte and platelet populations independently, as well as simultaneously without prior isolation. We find that murine lymphocytes exhibit temperature-dependent IDT307 transport but uptake is independent of SERT. Lack of measurable SERT function in lymphocytes was corroborated by chronoamperometry using serotonin as a substrate. When we examined rhesus and human mixed blood cell populations, we found that platelets, and not lymphocytes,were primary contributors to SERT function. Overall, these findingsindicate that lymphocyte SERT function is minimal. Moreover, flowcytometry, in conjunction with the fluorescent transporter substrateIDT307, can be widely applied to investigate SERT in platelets frompopulations of clinical significance.
机译:血清素转运蛋白(SERT)是许多抗抑郁药的主要靶标,它在大脑和外周血细胞中都有表达。尽管血小板SERT功能已被广泛接受,但淋巴细胞SERT功能尚未得到明确的表征。由于血小板小,通常在外周血单核细胞制剂中发现血小板,目的是分离淋巴细胞,单核细胞和巨噬细胞。不同细胞的存在使得难以将SERT表达和功能分配给特定细胞类型。在这里,我们使用流式细胞仪和IDT307(一种吸收到细胞后发出荧光的单胺转运蛋白底物)来独立研究淋巴细胞和血小板群体中SERT的功能,以及同时研究其在没有事先分离的情况下的功能。我们发现鼠类淋巴细胞表现出温度依赖性的IDT307运输,但摄取与SERT无关。以5-羟色胺为底物的计时电流法证实了淋巴细胞中缺乏可测量的SERT功能。当我们检查恒河猴和人类混合血细胞的数量时,我们发现血小板而不是淋巴细胞是SERT功能的主要贡献者。总体而言,这些发现表明淋巴细胞的SERT功能微弱。而且,流量细胞计数,结合荧光转运蛋白底物IDT307可广泛用于研究血小板来源的SERT具有临床意义的人群。

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