Detection of inflammatory cell function using (13)C magnetic resonance spectroscopy of hyperpolarized [6-(13)C]-arginine.
Detection of inflammatory cell function using (13)C magnetic resonance spectroscopy of hyperpolarized [6-(13)C]-arginine.
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使用超极化 [6-(13)C]-精氨酸的 (13)C 磁共振波谱检测炎症细胞功能。
DOI：
10.1038/srep31397
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发表时间：
2016
影响因子：
4.6
通讯作者：
Ronen,SabrinaM
中科院分区：
文献类型：
--
作者：
Najac,Chloé;Chaumeil,MyriamM;Kohanbash,Gary;Guglielmetti,Caroline;Gordon,JeremyW;Okada,Hideho;Ronen,SabrinaM
髓源性抑制细胞（MDSCs）是一种非常普遍的炎症细胞，在肿瘤发展中起着关键作用，被认为是治疗靶点。MDSCs通过消耗对t细胞增殖至关重要的精氨酸来阻断t细胞介导的抗肿瘤免疫反应，从而促进肿瘤生长。为了消耗精氨酸，MDSCs表达高水平的精氨酸酶，该酶催化精氨酸分解为尿素和鸟氨酸。在这里，我们开发了一种新的超极化13c探针，[6-13C]-精氨酸，用于检测精氨酸酶的活性。我们发现[6-13C]-精氨酸可以被超极化，而[6-13C]-精氨酸的尿素产量与精氨酸酶浓度在体外呈线性相关。此外，我们表明，与对照骨髓细胞相比，我们可以检测到MDSCs中超极化[13C]-尿素产生的统计学显著增加。这种增加与使用分光光度法检测细胞内精氨酸酶浓度的增加有关。因此，超极化[6-13C]-精氨酸可以成像肿瘤MDSC功能和更广泛的m2样巨噬细胞。
Myeloid-derived suppressor cells (MDSCs) are highly prevalent inflammatory cells that play a key role in tumor development and are considered therapeutic targets. MDSCs promote tumor growth by blocking T-cell-mediated anti-tumoral immune response through depletion of arginine that is essential for T-cell proliferation. To deplete arginine, MDSCs express high levels of arginase, which catalyzes the breakdown of arginine into urea and ornithine. Here, we developed a new hyperpolarized13C probe, [6-13C]-arginine, to image arginase activity. We show that [6-13C]-arginine can be hyperpolarized and hyperpolarized [13C]-urea production from [6-13C]-arginine is linearly correlated with arginase concentrationin vitro. Furthermore we show that we can detect a statistically significant increase in hyperpolarized [13C]-urea production in MDSCs when compared to control bone marrow cells. This increase was associated with an increase in intracellular arginase concentration detected using a spectrophotometric assay. Hyperpolarized [6-13C]-arginine could therefore serve to image tumoral MDSC function and more broadly M2-like macrophages.