CXCR4 antagonist AMD3100 redistributes leukocytes from primary immune organs to secondary immune organs, lung, and blood in mice.
CXCR4 antagonist AMD3100 redistributes leukocytes from primary immune organs to secondary immune organs, lung, and blood in mice.
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DOI：
10.1002/eji.201445245
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发表时间：
2015-06
影响因子：
5.4
通讯作者：
Murphy, Philip M.
中科院分区：
文献类型：
--
作者：
Liu, Qian;Li, Zhanzhuo;Gao, Ji-Liang;Wan, Wuzhou;Ganesan, Sundar;McDermott, David H.;Murphy, Philip M.
AMD3100(Plerixafor)，是FDA批准的一种特异性CXCR4拮抗剂，用于动员骨髓中的造血干细胞到血液中用于癌症移植。AMD3100还可以动员大多数成熟的白细胞亚群进入血液；然而，它们的来源和贩运潜力尚未完全确定。在这里，我们展示了单次注射AMD3100 10 mg/kg给C57BL/6小鼠迅速动员(峰值~2.5小时)与人类相同的白细胞亚群到血液中。使用这个模型，我们发现AMD3100对中性粒细胞、淋巴细胞和单核细胞的动员不会因为脾切除或FTY720阻断淋巴出口而减少，而是与以下因素有关：1)骨髓中这些细胞类型的含量减少；2)胸腺中的T细胞数量减少；3)淋巴结中的淋巴细胞增加；以及4)肺中的中性粒细胞和单核细胞含量增加。胸腺内直接标记显示，AMD3100选择性地动员胸腺幼稚的CD4+和CD8+T细胞进入血液。最后，AMD3100诱导的中性粒细胞动员到血液中并没有减少中性粒细胞向硫代乙醇酸盐炎症腹膜的转运。因此，AMD3100将淋巴细胞、单核细胞和中性粒细胞从初级免疫器官重新分配到次级免疫器官、外周组织和血液，而不影响中性粒细胞向炎症部位的运输。
AMD3100 (plerixafor), is a specific CXCR4 antagonist approved by the FDA for mobilizing hematopoietic stem cells from bone marrow to blood for transplantation in cancer. AMD3100 also mobilizes most mature leukocyte subsets to blood; however, their source and trafficking potential have not been fully delineated. Here, we show that a single injection of AMD3100 10 mg/kg into C57Bl/6 mice rapidly mobilizes (peak ~ 2.5 hours) the same leukocyte subsets to blood as in humans. Using this model, we found that AMD3100 mobilization of neutrophils, lymphocytes and monocytes to blood isn’t reduced by splenectomy or by blockade of lymphocyte egress from lymph node with FTY720, but is coupled to i) reduced content of each of these cell types in the bone marrow; ii) reduced T-cell numbers in thymuses; iii) increased lymphocytes in lymph nodes; and iv) increased neutrophil and monocyte content in the lung. Direct intrathymic labeling showed that AMD3100 selectively mobilizes naïve thymic CD4+ and CD8+ T cells to blood. Finally, AMD3100-induced neutrophil mobilization to blood did not reduce neutrophil trafficking to thioglycollate-inflamed peritoneum. Thus, AMD3100 redistributes lymphocytes, monocytes and neutrophils from primary immune organs to secondary immune organs, peripheral tissues and blood, without compromising neutrophil trafficking to inflamed sites.
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DOI：
10.1084/jem.20092210
发表时间：
2010-05-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Allende ML;Tuymetova G;Lee BG;Bonifacino E;Wu YP;Proia RL
通讯作者：
Proia RL
影响因子：
11.4
作者：
Dar, A.;Schajnovitz, A.;Lapid, K.;Kalinkovich, A.;Itkin, T.;Ludin, A.;Kao, W-M;Battista, M.;Tesio, M.;Kollet, O.;Cohen, N. N.;Margalit, R.;Buss, E. C.;Baleux, F.;Oishi, S.;Fujii, N.;Larochelle, A.;Dunbar, C. E.;Broxmeyer, H. E.;Frenette, P. S.;Lapidot, T.
通讯作者：
Lapidot, T.
影响因子：
20.3
作者：
Eash, Kyle J.;Means, Jacquelyn M.;Link, Daniel C.
通讯作者：
Link, Daniel C.
影响因子：
45.3
作者：
Devine, SM;Flomenberg, N;DiPersio, JF
通讯作者：
DiPersio, JF
影响因子：
15.9
作者：
Eash, Kyle J.;Greenbaum, Adam M.;Link, Daniel C.
通讯作者：
Link, Daniel C.