Is there a direct effect of antithymocyte globulin on hematopoiesis?
Is there a direct effect of antithymocyte globulin on hematopoiesis?
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抗胸腺细胞球蛋白对造血有直接影响吗？
DOI：
10.1038/sj.thj.6200398
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Maciejewski,JaroslawP
中科院分区：
文献类型：
--
作者：
Chen,Guibin;Kook,Hoon;Zeng,Weihua;Young,NealS;Maciejewski,JaroslawP
免疫抑制治疗再生障碍性贫血（AA）的疗效为支持其免疫介导的病理生理学提供了最有力的论据。虽然抗胸腺细胞球蛋白（ATG）的几种免疫抑制作用可以在体外得到证实，但一些报告暗示，AA中ATG的活性可能是由于各种积极的造血作用。本文研究了马（h）和兔（r）ATG对体外培养骨髓祖细胞的影响。两种类型的ATG都与CD 34细胞结合，并且在用总骨髓细胞进行的集落测定中，hATG具有剂量依赖性的三相效应，在1和10 μ g/ml之间集落形成的最大增加和在100和1000 μ g/ml之间的抑制。如使用CD 34细胞所确定的，这些效应不需要辅助细胞。rATG显示类似的活性，但比hATG强约10倍。在存在补体的情况下，未观察到细胞毒性增加。在与输注后立即在患者中测量的浓度相当的浓度下，ATG显示出对集落形成的中度抑制，而体外刺激浓度对应于ATG给药后前几周内在体内观察到的浓度。在对照实验中，免疫前rIgG或hIgG制剂的生物学效应的模式与rATG和hATG的生物学效应的模式相似，表明ATG对祖细胞的作用具有非特异性。在甲基纤维素培养物中观察到F（ab）（2）片段的生物活性，但在纯化的Fc IgG中未发现。总之，ATG对造血祖细胞的作用谱依赖于ATG的浓度，可能与其抗原特异性无关。
The efficacy of immunosuppressive therapy in aplastic anemia (AA) provides the strongest argument to support its immune-mediated pathophysiology. While several immunosuppressive effects of antithymocyte globulin (ATG) can be demonstrated in vitro, some reports have implied that the activity of ATG in AA may be rather due to a variety of positive hematopoietic effects. We studied the effects of horse (h) and rabbit (r) ATG on marrow progenitors in vitro. Both types of ATG bound to CD34 cells and, in colony assays performed with total marrow cells, hATG had a dose-dependent, triphasic effect, with maximal increase in colony formation between 1 and 10 microg/ml and inhibition between 100 and 1000 microg/ml. As determined using CD34 cells, these effects did not require accessory cells. rATG showed similar activity, but was about 10-fold more potent than hATG. In the presence of complement, no increased cytotoxicity was observed. At concentrations equivalent to those measured in patients immediately after infusion, ATG showed moderate suppression of colony formation, while the stimulatory concentrations in vitro correspond to those seen in vivo within the first weeks after ATG administration. In control experiments, the patterns of the biologic effects of preimmune rIgG or hIgG preparations were similar to those of rATG and hATG, indicating a nonspecific nature of the effects of ATG on progenitor cells. Biological activity in methylcellulose cultures was observed with the F (ab)(2) fragments but was not found in purified Fc IgG. In summary, the spectrum of effects of ATG on hematopoietic progenitors is dependent upon the concentrations of ATG and may not be related to its antigenic specificity.