Neutralization of interferon-gamma exacerbates pneumocystis-driven interstitial pneumonitis after bone marrow transplantation in mice.

Neutralization of interferon-gamma exacerbates pneumocystis-driven interstitial pneumonitis after bone marrow transplantation in mice.
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小鼠骨髓移植后,干扰素-γ的中和会加剧肺孢子虫引起的间质性肺炎。

DOI:
10.1172/jci119326
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发表时间:
1997
期刊:
The Journal of clinical investigation.
影响因子:
--
通讯作者:
Harmsen,AG
Harmsen,AG
中科院分区:
--
文献类型:
--
作者:
Garvy,BA;Gigliotti,F;Harmsen,AG

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在小鼠移植物抗宿主病模型中,研究了干扰素-γ在感染驱动的间质性肺炎发展中的作用。在卡氏肺孢子虫感染的同时,小鼠接受了同基因或异基因骨髓移植,并接受了对照单抗或抗IFNGamma单抗治疗。在移植后第21天,所有组的肺重量都增加了近两倍。到第41天,所有组的小鼠都清除了卡氏肺孢子虫,但只有接受同种异体移植和抗IFNGamma的小鼠肺重量增加。与对照组相比,抗IFNGamma组小鼠肺重量增加与嗜酸性粒细胞、中性粒细胞和多核巨细胞的肺泡渗透相对应,并加重了间质性肺炎。细胞内染色显示,在接受同基因或异基因移植的小鼠的肺灌洗液中,产生干扰素-伽马的CD4+细胞比产生IL-4的细胞多3-10倍。小鼠肺灌洗液中产生干扰素-γ的CD4+和CD8+细胞显著减少,而产生IL-4的CD4+细胞的数量无明显变化。这些数据表明,在小鼠同基因或异基因骨髓移植后,干扰素-γ对于控制卡氏肺孢子虫引起的间质性肺炎的发展至关重要。
The role of IFNgamma in the development of infection-driven interstitial pneumonitis in a model of murine graft-versus-host disease was investigated. Mice were given either syngeneic or allogeneic bone marrow transplants along with lung Pneumocystis carinii infections and were treated with either control mAb or anti-IFNgamma mAb. At day 21 after transplant, lung weights were elevated nearly twofold in all groups. By day 41, mice in all groups had cleared the P. carinii but only the mice given allogeneic transplants and anti-IFNgamma had increased lung weights. Increased lung weights in the anti-IFNgamma-treated mice corresponded to alveolar infiltration of eosinophils, neutrophils, and multinucleated giant cells and exacerbated interstitial pneumonitis compared with mice treated with control antibody. Intracellular staining indicated that there were 3- to 10-fold more CD4+ cells producing IFNgamma than those producing IL-4 in the lung lavages of mice given either syngeneic or allogeneic transplant. Treatment of transplanted mice with anti-IFNgamma resulted in a significant decrease in IFN-gamma-producing CD4+ and CD8+ cells in the lung lavages but no change in the number of IL-4-producing CD4+ cells. These data indicate that IFNgamma is critical for controlling the development of P. carinii-driven interstitial pneumonia after either syngeneic or allogeneic bone marrow transplant in mice.
DOI: 10.1084/jem.182.5.1357
发表时间: 1995-11-01
期刊: The Journal of experimental medicine
影响因子: --
作者:
Openshaw P;Murphy EE;Hosken NA;Maino V;Davis K;Murphy K;O'Garra A
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发表时间: 1994
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影响因子: 6.2
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DOI: --
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