Accumulation of natural killer cells in ischemic brain tissues and the chemotactic effect of IP-10.
Accumulation of natural killer cells in ischemic brain tissues and the chemotactic effect of IP-10.
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缺血脑组织中自然杀伤细胞的积累及IP-10的趋化作用
DOI：
10.1186/1742-2094-11-79
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发表时间：
2014-04-17
影响因子：
9.3
通讯作者：
Wang G
中科院分区：
文献类型：
--
作者：
Zhang Y;Gao Z;Wang D;Zhang T;Sun B;Mu L;Wang J;Liu Y;Kong Q;Liu X;Zhang Y;Zhang H;He J;Li H;Wang G
背景中风伴随着由免疫细胞浸润、细胞因子表达和其他炎症介质引发的明显炎症反应。由于自然杀伤细胞（NK细胞）是一种对先天免疫系统至关重要的细胞毒性淋巴细胞，我们同时研究了NK细胞诱导脑缺血后脑损伤的机制以及IP-10的趋化作用。方法采用免疫组化、免疫荧光、PCR和流式细胞术检测人和C57/BL6野生型小鼠缺血脑组织中NK细胞的浸润、干扰素γ（IFN-γ）和IP-10的表达。通过2,3,5-三苯基氯化四唑染色检测缺血区域。通过流式细胞术测量分离的 NK 细胞的 CXCR3 平均荧光强度。通过细胞凋亡实验检测NK细胞对神经元的损伤。通过迁移和通透性测定来检测IP-10的趋化性。结果在人缺血脑组织中，观察到NK细胞的浸润，并在2至5天时达到峰值。在永久性大脑中动脉闭塞 (pMCAO) 模型中，缺血性梗塞区域的 NK 细胞浸润在缺血后 12 小时达到最高水平。 pMCAO 进行后 6 小时至 4 天，在缺血区域内也检测到了 IFN-γ 阳性 NK 细胞和趋化因子 IP-10 的水平，并且体内 NK 细胞耗尽后 IFN-γ 水平下降。神经细胞与 NK 细胞的共培养实验也表明，神经坏死是通过 IFN-γ 诱导的。在IP-10的平行实验中，CXCR3的存在表明NK细胞通过CXCR3受到IP-10的影响，并且效果呈剂量依赖性。体内IP-10耗尽后，NK细胞减少。在迁移测定和渗透性实验中，添加 NK 细胞后观察到血脑屏障 (BBB) 崩解。而且，在IP-10存在的情况下，这种损伤加剧。结论所有研究结果都支持NK细胞参与脑缺血并通过IFN-γ促进神经细胞坏死的假设。此外，IP-10 通过 CXCR3 加剧 NK 细胞对 BBB 的损伤。
BackgroundStroke is accompanied by a distinguished inflammatory reaction that is initiated by the infiltration of immunocytes, expression of cytokines, and other inflammatory mediators. As natural killer cells (NK cells) are a type of cytotoxic lymphocyte critical to the innate immune system, we investigated the mechanism of NK cells-induced brain injuries after cerebral ischemia and the chemotactic effect of IP-10 simultaneously.MethodsNK cells infiltration, interferon-gamma (IFN-γ) and IP-10 expression were detected by immunohistochemistry, immunofluorescence, PCR and flow cytometry in human and C57/BL6 wild type mouse ischemic brain tissues. The ischemia area was detected via 2,3,5-triphenyltetrazolium chloride staining. CXCR3 mean fluorescence intensity of isolated NK cells was measured by flow cytometry. The neuronal injury made by NK cells was examined via apoptosis experiment. The chemotactic of IP-10 was detected by migration and permeability assays.ResultsIn human ischemic brain tissue, infiltrations of NK cells were observed and reached a peak at 2 to 5 days. In a permanent middle cerebral artery occlusion (pMCAO) model, infiltration of NK cells into the ischemic infarct region reached their highest levels 12 hours after ischemia. IFN-γ-positive NK cells and levels of the chemokine IP-10 were also detected within the ischemic region, from 6 hours up to 4 days after pMCAO was performed, and IFN-γ levels decreased after NK cells depletionin vivo. Co-culture experiments of neural cells with NK cells also showed that neural necrosis was induced via IFN-γ. In parallel experiments with IP-10, the presence of CXCR3 indicates that NK cells were affected by IP-10 via CXCR3, and the effect was dose-dependent. After IP-10 depletionin vivo, NK cells decreased. In migration assays and permeability experiments, disintegration of the blood–brain barrier (BBB) was observed following the addition of NK cells. Moreover, in the presence of IP-10 this injury was aggravated.ConclusionsAll findings support the hypothesis that NK cells participate in cerebral ischemia and promote neural cells necrosis via IFN-γ. Moreover, IP-10 intensifies injury to the BBB by NK cells via CXCR3.
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影响因子：
3.3
作者：
Chaitanya, G. V.;Schwaninger, M.;Babu, P. Prakash
通讯作者：
Babu, P. Prakash
DOI：
10.1126/science.1198687
发表时间：
2011-01-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Vivier E;Raulet DH;Moretta A;Caligiuri MA;Zitvogel L;Lanier LL;Yokoyama WM;Ugolini S
通讯作者：
Ugolini S
DOI：
10.1073/pnas.0601335103
发表时间：
2006-04-11
影响因子：
11.1
作者：
Bielekova, B;Catalfamo, M;Martin, R
通讯作者：
Martin, R
影响因子：
8.3
作者：
Gelderblom, Mathias;Leypoldt, Frank;Magnus, Tim
通讯作者：
Magnus, Tim
DOI：
10.1084/jem.20021098
发表时间：
2003-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Prass K;Meisel C;Höflich C;Braun J;Halle E;Wolf T;Ruscher K;Victorov IV;Priller J;Dirnagl U;Volk HD;Meisel A
通讯作者：
Meisel A