Laboratory of Experimental Hematology, Institute of Biophysics, vvi, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
Purinergic Signal. 2013 Jun;9(2):207-14. doi: 10.1007/s11302-012-9340-5. Epub 2012 Dec 15.
This study continues our earlier findings on the hematopoiesis-modulating effects of adenosine A1 and A3 receptor agonists that were performed on committed hematopoietic progenitor and precursor cell populations. In the earlier experiments, N (6)-cyclopentyladenosine (CPA), an adenosine A1 receptor agonist, was found to inhibit proliferation in the above-mentioned hematopoietic cell systems, whereas N (6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA), an adenosine A3 receptor agonist, was found to stimulate it. The topic of this study was to evaluate the possibility that the above-mentioned adenosine receptor agonists modulate the behavior of early hematopoietic progenitor cells and hematopoietic stem cells. Flow cytometric analysis of hematopoietic stem cells in mice was employed, as well as a functional test of hematopoietic stem and progenitor cells (HSPCs). These techniques enabled us to study the effect of the agonists on both short-term repopulating ability and long-term repopulating ability, representing multipotent progenitors and hematopoietic stem cells, respectively. In a series of studies, we did not find any significant effect of adenosine agonists on HSPCs in terms of their numbers, proliferation, or functional activity. Thus, it can be concluded that CPA and IB-MECA do not significantly influence the primitive hematopoietic stem and progenitor cell pool and that the hematopoiesis-modulating action of these adenosine receptor agonists is restricted to more mature compartments of hematopoietic progenitor and precursor cells.
本研究延续了我们之前关于腺苷 A1 和 A3 受体激动剂对造血作用的研究结果,这些研究是在定向造血祖细胞和前体细胞群上进行的。在之前的实验中,发现腺苷 A1 受体激动剂 N(6)-环戊基腺苷(CPA)抑制上述造血细胞系统的增殖,而腺苷 A3 受体激动剂 N(6)-(3-碘苄基)腺苷-5'-N-甲基尿苷酰胺(IB-MECA)刺激其增殖。本研究的主题是评估上述腺苷受体激动剂是否有可能调节早期造血祖细胞和造血干细胞的行为。我们采用了流式细胞术分析小鼠造血干细胞,并进行了造血干细胞和祖细胞(HSPCs)的功能测试。这些技术使我们能够研究激动剂对短期再殖能力和长期再殖能力的影响,分别代表多能祖细胞和造血干细胞。在一系列研究中,我们没有发现腺苷激动剂对 HSPCs 的数量、增殖或功能活性有任何显著影响。因此,可以得出结论,CPA 和 IB-MECA 对原始造血干细胞和祖细胞池没有显著影响,这些腺苷受体激动剂对造血的调节作用仅限于造血祖细胞和前体细胞的更成熟部分。