The aim of the study was to investigate the sensitivity of AHH-1 human lymphoblastoid cells to radiation and its relevance to intracellular events, specifically alteration in cellular energy-producing systems. AHH-1 human lymphoblastoid cells were irradiated with 6 Gy of gamma radiation, and then were collected at the indicated time points. Parallel studies were conducted to assess the effects of radiation on the cell proliferation and apoptotic index. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production were monitored. A marked decrease of cell viability was observed as early as 12 h postirradiation and fraction of apoptotic cells was highest at 24 It. Intracellular ROS generation measured with 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) appeared to be highest as early as 30 min postirradiation and resumed to normal level at 6 h. Unexpectedly, the fluorescence intensity of Rhodamine 123 for measuring NIMP did not change during the first 3 h afterradiation and exhibited an aberrant increase at 6 It. The results suggestthat AHH-1 cells are sensitive to radiation-induced apoptosis and ROS generation is an early phase in the apoptosis process. Moreover, the results might cast doubts on those studies using Rhodamine 123 which hypothesized that the fall in NIMP is one of the early events of apoptosis. (c) 2007 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.

AIM:To investigate the changes of lymphocyte subpopulations, especially CD4 + CD25 + T regulatory cells in Smad3 -/-mice. METHODS:Hematological changes and changes of lymphocyte subpopulations were detected in Smad3 -/-mice using cell counter and flow cytometry, respectively, and compared to their littermate controls. RESULTS:The numbers of neutrophils and lymphocytes in peripheral blood were significantly increased in Smad3 -/-mice compared to littermate controls.CD19 + expressing cells in blood and spleen, and CD8 + T cells in thymus were all markedly decreased in Smad3 -/-mice.More important, Smad3 -/-mice had an increased population of CD4 + CD25 + T cells in peripheral lymphoid tissues, including thymus, spleen, and lymph nodes. CONCLUSION:These observations suggest that the changes of lymphocyte subpopulations might play a role in susceptibility to inflammation of Smad3 -/-mice.

Bcl-xL belongs to a family of proteins which inhibit apoptosis in a number of stimuli including ionizing radiation. To better understand the effects and mechanisms of Bcl-xL on the apoptosis of lymphocytes and provide experimental basis to treat immune injury induced by radiation, we used normal human lymphoblastoid AHH-1 cells that were engineered to overexpress Bcl-xL proteins. Our results showed that overexpressed Bcl-xL reduced time-dependent increase of apoptosis induced by ionizing radiation. Reactive oxygen species (ROS) generation and Bax protein expression in the transfected AHH1-Bcl-xL cells were also lower compared to parental AHH-1 cells. Unexpectedly, the fluorescence intensity of Rhodomine 123 (Rh 123) for measuring mitochondrial membrane potential (MMP) did not change at all detected time points. These results possess a vital significance for insights into a new strategy for gene therapy of radiation-induced immune injury.

目的:已知射线能引起免疫系统损伤,为此观察急性大剂量γ射线照射后小鼠外周血淋巴细胞的凋亡机制及与免疫功能的关系.方法:用原位末端标记、原位杂交和碱磷酶免疫组化技术观察急性大剂量γ射线照射小鼠外周血淋巴细胞凋亡特征,bax,bcl-2和bcl-XL的表达及T细胞亚群的变化.结果:①照射后,白细胞数迅速下降.而淋巴细胞凋亡率持续升高,7 d达到峰值,12个月仍未恢复到正常值.照后24 h在6～12Gy范围内呈较好的剂量效应关系,≥15 Gy照射后凋亡率降低.②6 Gy照后24 h,淋巴细胞Bax蛋白表达即出现升高,当剂量为12 Gy时达到峰值,≥15 Gy照射后出现降低;而Bcl-2和Bcl-XL蛋白表达在照后24 h明显下降,于12 Gy照射后降至最低.Bax和Bcl-2 mRNA的表达显示出相似的变化趋势.③照后3 d,随照射剂量的增加T细胞及其亚群急剧降低,呈较好的剂量效应关系.结论:≤12 Gy照射后细胞凋亡是淋巴细胞的主要死亡方式.照射后Bax的上调及Bcl-XL的下调在急性大剂量照射引起的淋巴细胞凋亡和免疫调控中起重要作用.

Apoptosis or programmed cell death is an active form of cell death which is essential for tissue homeostasis. Many proteins are involved in the molecular signal transduction of apoptosis. The caspase enzymes, a family of specific cysteine proteases, play a central role in cell death machinery. In this review, we mainly discuss the current understanding of several pathways to activate caspases and some key proteins related to these pathways.

炎症性肠病(inflammatoryboweldisease,IBD)发病机制及治疗问题一直是临床和基础科学家困扰的问题.直至目前为止对其病因仍不清楚.IBD包括溃疡性结肠炎(ulcerativecolitis,UC)和克罗恩氏病(Crohn’sdisease,CD),前者是一种慢性非特异性结肠炎症,重者发生溃疡甚至癌变;病变主要累及结肠黏膜和黏膜下层,临床主要表现为腹泻、腹痛和黏液脓血便.后者病变可累及胃肠道各部位,是一种慢性肉芽肿性炎症,呈阶段性分布,主要临床表现为腹痛、腹泻、瘘管及不同程度的全身症状.本综述从IBD发病的病因学,Th1和Th2亚群及炎症细胞因子、调节性T细胞在其中的作用等方面简述了该领域的研究进展,期望能对从事该领域的研究者在探索IBD的发病机制和治疗策略方面有所郫益.

细胞凋亡实际上是细胞死亡的一种特殊方式,它在机体的组织发生、细胞分化、免疫应答和肿瘤发生等多种病理生理过程中发挥着重要作用.