Transfer of human leukocytes into double-knockout Pfp-/-Rag2-/- mice grafted with human skin: increased accumulation of neutrophils in human dermal microvessels.

Transfer of human leukocytes into double-knockout Pfp-/-Rag2-/- mice grafted with human skin: increased accumulation of neutrophils in human dermal microvessels.
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将人白细胞转移到移植有人皮肤的双敲除 Pfp-/-Rag2-/- 小鼠中:人真皮微血管中中性粒细胞的积累增加。

DOI:
10.1097/01.tp.0000144326.75485.b9
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发表时间:
2004
期刊:
影响因子:
6.2
通讯作者:
E. Csernok
E. Csernok
中科院分区:
医学2区
文献类型:
--
作者:
S. Ullrich;U. Schumacher;M. Ai;B. Tiemann;S. Gay;J. S. Schechner;J. Pober;W. Gross;E. Csernok

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用人类白细胞重组的严重联合免疫缺陷小鼠可用于模拟部分人类免疫系统,包括其某些疾病(如艾滋病)。由于在这些异种移植物模型中没有人类多形核白细胞(human polymorphonuclear leukocyte, huPMN)发育,因此不能使用这种方法来模拟诸如几种形式的血管炎等疾病。为了为血管炎提供这样的模型,我们将人类皮肤贴片移植到双敲除Pfp(-/-)Rag2(-/-)小鼠身上,这些小鼠不仅缺乏功能性T细胞和B细胞,而且也缺乏自然杀伤细胞。经静脉注射后,高比例的人类pmn在循环中存活并积聚在人类血管中。肿瘤坏死因子- α刺激皮肤斑块内皮细胞后,其积累明显增加。皮肤斑块微血管可见α -轻度血管周围嗜中性粒细胞浸润及血管坏死。因此,首次建立了以人类pmns浸润为主的血管炎异种移植模型。
Severe combined immunodeficient mice reconstituted with human leukocytes have been useful to model parts of the human immune system, including some of its diseases (e.g., AIDS). Because no human polymorphonuclear leukocytes (huPMN) develop in these xenograft models, diseases such as several forms of vasculitis cannot be modeled using this approach. To provide such a model for vasculitis, human skin patches were grafted onto double-knockout Pfp(-/-)Rag2(-/-) mice, which not only lack functional T and B cells but which are also devoid of natural killer cells. After intravenous injection, a high proportion of huPMNs survived within the circulation and accumulated in the human blood vessels. The accumulation increased considerably after the endothelium of the skin patches had been stimulated by tumor necrosis factor-alpha. Alpha mild perivascular neutrophilic infiltration and vascular necrosis was observed in the microvessels of the skin patches. Thus, a xenograft model of vasculitis with predominant huPMNs infiltration has been established for the first time.
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