免疫因子对血小板生成素的负调节作用

Down-regulation Thrombopoiesis by Immunocytokines in a Model of Gene Delivery

鉴于ＴＰＯ 在体内长期表达会给机体带来一些负面影响，以及在较长期作用模式下，机体血小板的生成能力与ＴＰＯ 在体内水平的不一致，本文对免疫因子与ＴＰＯ 表达及其生物活性间的关系进行了研究。在ＴＰＯ ｃＤＮＡ 转移到体内后，血液中ＩＦＮ－γ、ＴＮＦ－ α和ＩＬ－２ 迅速升高。其中，ＩＦＮ－γ与血小板计数呈明显负相关， 在血小板计数回落后保持在对照水平的 ９～１２ 倍；ＴＮＦ－α仅在第 １ 周内与之成正相关，且可达对照水平的１２０ 倍，此后局限于对照水平；ＩＬ－２ 升高幅度较小，与ＴＰＯ 的变化相一致。另外，血液中Ⅱ型组织相容性抗原分子也呈升高趋势，与ＩＬ－２ 的变化类似；而Ⅰ型分子与ＴＮＦ－ α的变化相似。结合基因转移后的组织学特点，可以认为ＩＦＮ－γ在血小板生成过程中起主要的逆向调节作用，而机体出现了以巨噬细胞、内皮细胞和Ｔ

Plasmid mediated gene transference is a promising alternative for thrombopoietin( TPO) delivery, however, long term in vivo expression of TPO is in some extent harmful to the experimental animals. In the model of plasmid mediated gene delivery, discordance between TPO expression level and the thrombopoiesis has been observed, that suggested some balance mechanisms be triggered. In this paper, we have investigated the relation between immunocytokines with the expression of TPO and its biologic activities. Soon after gene delivery, serum IFN γ、TNF α and IL 2 levels abruptly increased. Among them, IFN γ was negatively associated with platelet count(PLTC), in the stage of PLTC declination, it arrived to 9~12 folds that of the controls; although TNF α had reached 120 folds of the control in the first week, positively associated with the PLTC, it came silence since after; the increase in IL 2 had been in lesser extent, in accordance with the changes of TPO. Furthermore, class Ⅱ molecules of major histocompatibility were also increased in a similar pattern of IL 2; while classⅠmolecules showed no significant changes. Combined with the histological observations, it suggested that IFN-γ play key role in down regulation of the thrombopoiesis, and the animals be in an immunological active state that characterized as macrophage, endothelial cell and T lymphocyte activation.