Lymphocyte apoptosis in murine Pneumocystis pneumonia.

Lymphocyte apoptosis in murine Pneumocystis pneumonia.
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小鼠肺孢子虫肺炎中的淋巴细胞凋亡。

DOI:
10.1186/1465-9921-10-57
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发表时间:
2009-06-26
影响因子:
5.8
通讯作者:
Shellito, Judd E.
Shellito, Judd E.
中科院分区:
医学2区
文献类型:
--
作者:
Shi, Xin;LeCapitaine, Nicole J.;Rudner, Xiaowen L.;Ruan, Sanbao;Shellito, Judd E.

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淋巴细胞的凋亡在终止对感染的免疫应答中是重要的,但也已显示在全身性感染和脓毒症的动物模型中具有有害作用。我们试图描述肺孢子虫肺炎(一种局限于肺部的感染)动物模型中淋巴细胞凋亡的特征。对照小鼠和CD 4+淋巴细胞耗竭的小鼠接种肺孢子虫。流式细胞术和PCR检测肺、脾淋巴细胞凋亡蛋白。对照组小鼠肺组织淋巴细胞凋亡在感染清除后达到高峰,随后下降。然而,在CD 4-耗尽的小鼠中,尽管进行性感染,细胞凋亡也在募集的淋巴细胞中上调。脾淋巴细胞在接种后1周即出现凋亡,随后逐渐减少。对照组小鼠肺淋巴细胞凋亡与Bcl-2 mRNA的减少和Bim mRNA的增加有关。在CD 4-耗尽的小鼠中,灌洗的CD 8+细胞确实改变了细胞内Bcl-2,但显示Bim的mRNA增加。肺和肺外淋巴细胞的凋亡是正常宿主对肺孢子虫的反应的一部分,但在进行性感染的CD 4缺陷动物中也会引发凋亡。在正常小鼠中,肺淋巴细胞的凋亡可能起到终止肺组织免疫应答的作用。肺淋巴细胞的细胞凋亡通过内在和外在细胞凋亡途径发生,并与促细胞凋亡蛋白和抗细胞凋亡蛋白的变化相关。
Apoptosis of lymphocytes is important in the termination of an immune response to infection but has also been shown to have detrimental effects in animal models of systemic infection and sepsis. We sought to characterize lymphocyte apoptosis in an animal model of pneumonia due to Pneumocystis murina, an infection localized to the lungs. Control mice and mice depleted of CD4+ lymphocytes were inoculated with Pneumocystis. Apoptosis of lung and spleen lymphocytes was assayed by flow cytometry and PCR assay of apoptotic proteins. In control mice, apoptosis of lung lymphocytes was maximal just after the infection was cleared from lung tissue and then declined. However, in CD4-depleted mice, apoptosis was also upregulated in recruited lymphocytes in spite of progressive infection. In splenic lymphocytes, apoptosis was observed early at 1 week after inoculation and then declined. Apoptosis of lung lymphocytes in control mice was associated with a decrease in mRNA for Bcl-2 and an increase in mRNA for Bim. In CD4-depleted mice, lavaged CD8+ cells did change intracellular Bcl-2 but showed increased mRNA for Bim. Apoptosis of both pulmonary and extrapulmonary lymphocytes is part of the normal host response to Pneumocystis but is also triggered in CD4-deficient animals with progressive infection. In normal mice apoptosis of pulmonary lymphocytes may serve to terminate the immune response in lung tissue. Apoptosis of lung lymphocytes takes place via both the intrinsic and extrinsic apoptotic pathways and is associated with changes in both pro- and anti-apoptotic proteins.
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发表时间: 2003-03-01
期刊: IMMUNOLOGY
影响因子: 6.4
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发表时间: 2006-08-01
影响因子: 4.4
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