Impact of developmental lead exposure on splenic factors.
Impact of developmental lead exposure on splenic factors.
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DOI：
10.1016/j.taap.2010.06.003
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发表时间：
2010-09-01
影响因子：
3.8
通讯作者：
Lawrence DA
中科院分区：
文献类型：
--
作者：
Kasten-Jolly J;Heo Y;Lawrence DA
已知铅（Pb）会改变许多器官系统的功能，包括造血和免疫系统。铅可引起贫血，降低宿主对细菌和病毒感染的抵抗力。贫血是由于铅抑制血红蛋白的合成和铅的诱导膜的变化，导致早期红细胞衰老。铅还增加B细胞活化/增殖，并使T细胞辅助（Th）偏向Th 2亚群生成。许多铅的影响的具体机制，尚未完全理解。因此，我们通过微阵列对发育中铅暴露小鼠脾脏的RNA进行基因表达分析，以进一步了解这些铅影响。脾脏RNA微阵列分析表明，蛋白水解酶，脂肪酶，淀粉酶和RNaseA的基因编码的强烈上调。这些数据还表明，铅影响了许多与先天免疫相关的基因的表达。通过GeneSifter软件分析微阵列结果表明，铅增加细胞凋亡，B细胞分化，和Th 2的发展。铅直接上调血红素调节抑制因子（HRI）编码基因的表达，表明铅可通过阻断珠蛋白mRNA的翻译而降低红细胞生成。铅的高水平的消化/分解代谢酶可以产生免疫原性的自我肽。随着铅的潜力，以诱导新的自我肽，并提高半胱天冬酶，细胞因子和其他免疫调节剂的表达，进一步评估铅的参与自身免疫现象，特别是Th 2介导的自身抗体的产生，并改变器官系统的活动是必要的。
Lead (Pb) is known to alter the functions of numerous organ systems, including the hematopoietic and immune systems. Pb can induce anemia and can lower host resistance to bacterial and viral infections. The anemia is due to Pb’s inhibition of hemoglobin synthesis and Pb’s induction of membrane changes, leading to early erythrocyte senescence. Pb also increases B-cell activation/proliferation and skews T-cell help (Th) toward Th2 subset generation. The specific mechanisms for many of the Pb effects are, as yet, not completely understood. Therefore, we performed gene expression analysis, via microarray, on RNA from the spleens of developmentally Pb-exposed mice, in order to gain further insight into these Pb effects. Splenic RNA microarray analysis indicated strong up-regulation of genes coding for proteolytic enzymes, lipases, amylase, and RNaseA. The data also showed that Pb affected the expression of many genes associated with innate immunity. Analysis of the microarray results via GeneSifter software indicated that Pb increased apoptosis, B-cell differentiation, and Th2 development. Direct up-regulation by Pb of expression of the gene encoding the heme-regulated inhibitor (HRI) suggested that Pb can decrease erythropoiesis by blocking globin mRNA translation. Pb’s high elevation of digestive/catabolizing enzymes could generate immunogenic self peptides. With Pb’s potential to induce new self-peptides and to enhance the expression of caspases, cytokines, and other immunomodulators, further evaluation of Pb’s involvement in autoimmune phenomena, especially Th2-mediated autoantibody production, and alteration of organ system activities is warranted.
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DOI：
10.1073/pnas.89.13.6065
发表时间：
1992-07-01
影响因子：
11.1
作者：
HSIEH, CS;HEIMBERGER, AB;MURPHY, KM
通讯作者：
MURPHY, KM
DOI：
10.1080/15287390306456
发表时间：
2003-05-23
影响因子：
2.6
作者：
Hudson, CA;Cao, L;Lawrence, DA
通讯作者：
Lawrence, DA
影响因子：
3.6
作者：
Cosen-Binker, LI;Binker, MG;Tiscornia, O
通讯作者：
Tiscornia, O
Bcl6基因的破坏会导致生发中心形成受损。
DOI：
10.1084/jem.186.3.439
发表时间：
1997-08-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fukuda T;Yoshida T;Okada S;Hatano M;Miki T;Ishibashi K;Okabe S;Koseki H;Hirosawa S;Taniguchi M;Miyasaka N;Tokuhisa T
通讯作者：
Tokuhisa T
影响因子：
32.4
作者：
Kaplan, MH;Schindler, U;Grusby, MJ
通讯作者：
Grusby, MJ