Stepanova A A, Karpova Ya D, Bozhok G A, Ustichenko V D, Lyupina Yu V, Legach E I, Vagida M S, Kazansky D B, Bondarenko T P, Sharova N P
Bioorg Khim. 2014 Jan-Feb;40(1):42-54. doi: 10.1134/s1068162014010105.
The proteasomes in the liver of August rats (RT1C) were investigated 30 days after the allotransplantation of Wistar rat (RT1u) thyroid tissue under renal capsule with/without induction of donor specific tolerance by donor splenocyte intraportal administration. The level of the total proteasome pool, immune proteasomes containing the LMP2 and/or LMP7 subunits, proteasome 19S- and 11S-regulators was defined. The intact and sham-operated August rats were used as control groups. The level of all immune proteasome forms and 11S regulator increased while the level of the total proteasome pool and 19S regulator decreased in the liver of experimental animals compared to the control groups that indicated changes of liver functional state after transplantation. The 19S/11S ratio increased in the liver of non-tolerated rats compared to tolerated animals. In the liver of tolerated rats with survived transplants, the quantity of mononuclear cells, expressing the immune subunit LMP2, greatly increased in comparison with control and non-tolerated animals. Study of the survived transplants showed the increase of the ratio of LMP2/LMP7 immune subunits and 19S/11S regulators in them compared to the tissue replacing the rejected transplants. In the control intact thyroid tissue, the immune proteasomes were almost not revealed, while 19S/11S ratio was maximal. Thus, the development of the immune reaction or its suppression is accompanied by change of the balance between different proteasome forms. The immune subunit LMP7 and 11S regulator are connected with the response against donor tissue. On the contrary, the immune subunit LMP2 and 19S regulator are likely to be important for the immune tolerance development and survived tissue functioning. The low content of the immune proteasomes in the follicle cells was found by immunofluorescence assay. The formation of antigens for major histocompatibility complex class I molecules was impaired by low immune proteasome content that led to immunological tolerance to hormone-producing follicle cells.
在将Wistar大鼠（RT1u）甲状腺组织肾包膜下同种异体移植给八月龄大鼠（RT1C）30天后，研究了其肝脏中的蛋白酶体情况，移植时通过门静脉注射供体脾细胞诱导或不诱导供体特异性耐受。测定了总蛋白酶体库、含有LMP2和/或LMP7亚基的免疫蛋白酶体、蛋白酶体19S调节因子和11S调节因子的水平。将未处理的和假手术的八月龄大鼠作为对照组。与对照组相比，实验动物肝脏中所有免疫蛋白酶体形式和11S调节因子的水平升高，而总蛋白酶体库和19S调节因子的水平降低，这表明移植后肝脏功能状态发生了变化。与耐受大鼠相比，未耐受大鼠肝脏中的19S/11S比值升高。在移植存活的耐受大鼠肝脏中，表达免疫亚基LMP2的单核细胞数量与对照组和未耐受动物相比大幅增加。对存活移植组织的研究表明，与替代排斥移植组织的组织相比，其中LMP2/LMP7免疫亚基和19S/11S调节因子的比值升高。在对照的完整甲状腺组织中，几乎未检测到免疫蛋白酶体，而19S/11S比值最大。因此，免疫反应的发生或其抑制伴随着不同蛋白酶体形式之间平衡的变化。免疫亚基LMP7和11S调节因子与对供体组织的反应有关。相反，免疫亚基LMP2和19S调节因子可能对免疫耐受的形成和存活组织的功能很重要。通过免疫荧光分析发现卵泡细胞中免疫蛋白酶体含量较低。免疫蛋白酶体含量低会损害主要组织相容性复合体I类分子抗原的形成，从而导致对产生激素的卵泡细胞产生免疫耐受。
