Chronic restraint stress promotes lymphocyte apoptosis by modulating CD95 expression.
Chronic restraint stress promotes lymphocyte apoptosis by modulating CD95 expression.
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DOI：
10.1084/jem.191.8.1423
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发表时间：
2000-04-17
期刊：
影响因子：
--
通讯作者：
Shi Y
中科院分区：
文献类型：
--
作者：
Yin D;Tuthill D;Mufson RA;Shi Y
根据持续时间和严重程度，心理紧张和身体压力可以增强或抑制人类和动物的免疫系统。虽然压力会改变各种激素和神经递质的释放，但压力影响免疫反应的机制仍然难以捉摸。我们在这里报告说，小鼠进行慢性12小时每天物理约束两天表现出显着减少脾细胞，一个过程可能介导的细胞凋亡所证明的末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记试验。应激小鼠脾淋巴细胞CD 95（Fas/APO-1）表达显著增加。有趣的是，Fas-免疫球蛋白融合蛋白和针对CD 95配体的阻断抗体抑制应激诱导的淋巴细胞减少。应激诱导的CD 95表达和淋巴细胞数量的变化可以被特异性阿片受体拮抗剂纳洛酮或纳洛酮阻断，表明内源性阿片在此过程中起关键作用。此外，该模型系统中脾细胞的减少似乎与下丘脑-垂体-肾上腺轴无关，因为肾上腺切除和假手术小鼠对慢性应激表现出相似的反应。此外，慢性物理约束未能诱导CD 95缺陷（Faslpr/lpr）小鼠淋巴细胞数量的减少。因此，应激通过依赖于内源性阿片样物质的CD 95介导的细胞凋亡来调节免疫系统。
Depending on the duration and severity, psychological tension and physical stress can enhance or suppress the immune system in both humans and animals. Although it is well established that stress alters the release of various hormones and neurotransmitters, the mechanisms by which stress affects immune responses remain elusive. We report here that mice subjected to chronic 12-hour daily physical restraint for two days exhibited a significant reduction in splenocytes, a process likely mediated by apoptosis as demonstrated by the terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick end labeling assay. CD95 (Fas/APO-1) expression in splenic lymphocytes of stressed mice was substantially increased. Interestingly, Fas-immunoglobulin fusion protein and blocking antibodies against CD95 ligand inhibit stress-induced reduction in lymphocytes. The stress-induced changes in CD95 expression and lymphocyte number could be blocked by naltrexone or naloxone, specific opioid receptor antagonists, indicating a pivotal role of endogenous opioids in this process. In addition, the reduction of splenocytes in this model system seems to be independent of the hypothalamo-pituitary-adrenal axis, as both adrenalectomized and sham-operated mice exhibited similar responses to chronic stress. Moreover, chronic physical restraint failed to induce a decrease in lymphocyte numbers in CD95-deficient (Faslpr/lpr) mice. Therefore, stress modulates the immune system through CD95-mediated apoptosis dependent on endogenous opioids.
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DOI：
10.1073/pnas.96.3.1059
发表时间：
1999-02-02
影响因子：
11.1
作者：
Dhabhar, FS;McEwen, BS
通讯作者：
McEwen, BS
DOI：
10.1249/00005768-199402000-00001
发表时间：
1994-02-01
期刊：
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
影响因子：
--
作者：
NASH, MS
通讯作者：
NASH, MS
影响因子：
2.5
作者：
Nieman, DC
通讯作者：
Nieman, DC
DOI：
10.1073/pnas.95.12.7231
发表时间：
1998-06-09
影响因子：
11.1
作者：
Padgett, DA;Sheridan, JF;Glaser, R
通讯作者：
Glaser, R
DOI：
10.1093/dnares/2.4.167
发表时间：
1995-08-31
期刊：
DNA research : an international journal for rapid publication of reports on genes and genomes
影响因子：
--
作者：
Nagase, T;Seki, N;Nomura, N
通讯作者：
Nomura, N