Lymphocyte metabolism and cytotoxic activity monitored with 31P magnetic resonance spectroscopy.

K S Narayan, D M Freeman, E A Moress, M Ingram, B Ross
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Abstract

Continuous metabolic monitoring of human lymphocytes and a tumor cell line was achieved by means of nuclear magnetic resonance (NMR) applied to cells suspended in alginate gels. Human peripheral blood lymphocytes cultured in vitro were examined with 31P magnetic resonance spectroscopy (MRS) before and after activation with phytohemagglutinin and interleukin-2 (IL-2). Following the addition of these biological response modifiers, increases in [ATP], phosphomonoesters (PME), and phosphodiesters occurred. These appear to be markers of lymphocyte stimulation. Lymphocyte pH was unchanged. A target tumor cell line (K562) showed 31P NMR spectra that differed significantly from that of lymphocytes. When lymphocytes were mixed with tumor cells (to induce tumor cell death), and monitored by 31P MRS, levels of inorganic phosphate (Pi) increased, [PME] levels fell, and release of H+ was inhibited. 31P MRS may therefore provide a noninvasive assay of lymphocyte-mediated tumor cell killing that will have application in monitoring treatment in patients undergoing this type of therapy.

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用31P磁共振波谱法监测淋巴细胞代谢和细胞毒活性。
采用海藻酸盐凝胶悬浮细胞核磁共振(NMR)技术,实现了人淋巴细胞和肿瘤细胞系的连续代谢监测。采用体外培养的人外周血淋巴细胞经植物血凝素和白细胞介素-2 (IL-2)活化前后的31P磁共振波谱(MRS)检测。加入这些生物反应调节剂后,[ATP]、磷酸单酯(PME)和磷酸二酯增加。这些似乎是淋巴细胞刺激的标志。淋巴细胞pH不变。靶肿瘤细胞系K562的核磁共振31P谱与淋巴细胞有显著差异。当淋巴细胞与肿瘤细胞混合(诱导肿瘤细胞死亡),并通过31P MRS监测时,无机磷酸盐(Pi)水平升高,[PME]水平下降,H+释放受到抑制。因此,31P MRS可以提供一种无创的淋巴细胞介导的肿瘤细胞杀伤测定方法,将应用于接受这类治疗的患者的监测治疗。
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