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通过使用针对C-C趋化因子受体3(CCR3)的特异性抗体来耗尽小鼠体内的嗜酸性粒细胞。

Depletion of eosinophils in mice through the use of antibodies specific for C-C chemokine receptor 3 (CCR3).

作者信息

Grimaldi J C, Yu N X, Grunig G, Seymour B W, Cottrez F, Robinson D S, Hosken N, Ferlin W G, Wu X, Soto H, O'Garra A, Howard M C, Coffman R L

机构信息

DNAX Research Institute of Molecular & Cellular Biology, Palo Alto, California, USA.

出版信息

J Leukoc Biol. 1999 Jun;65(6):846-53. doi: 10.1002/jlb.65.6.846.

Abstract

We have generated rat monoclonal antibodies specific for the mouse eotaxin receptor, C-C chemokine receptor 3 (CCR3). Several anti-CCR3 mAbs proved to be useful for in vivo depletion of CCR3-expressing cells and immunofluorescent staining. In vivo CCR3 mAbs of the IgG2b isotype substantially depleted blood eosinophil levels in Nippostrongyus brasiliensis-infected mice. Repeated anti-CCR3 mAb treatment in these mice significantly reduced tissue eosinophilia in the lung tissue and bronchoalveolar lavage fluid. Flow cytometry revealed that mCCR3 was expressed on eosinophils but not on stem cells, dendritic cells, or cells from the thymus, lymph node, or spleen of normal mice. Unlike human Th2 cells, mouse Th2 cells did not express detectable levels of CCR3 nor did they give a measurable response to eotaxin. None of the mAbs were antagonists or agonists of CCR3 calcium mobilization. To our knowledge, the antibodies described here are the first mAbs reported to be specific for mouse eosinophils and to be readily applicable for the detection, isolation, and in vivo depletion of eosinophils.

摘要

我们已经制备了针对小鼠嗜酸性粒细胞趋化因子受体C-C趋化因子受体3(CCR3)的大鼠单克隆抗体。几种抗CCR3单克隆抗体被证明可用于体内清除表达CCR3的细胞以及免疫荧光染色。IgG2b同种型的体内CCR3单克隆抗体可显著降低巴西日圆线虫感染小鼠的血液嗜酸性粒细胞水平。在这些小鼠中重复进行抗CCR3单克隆抗体治疗可显著降低肺组织和支气管肺泡灌洗液中的组织嗜酸性粒细胞增多现象。流式细胞术显示,mCCR3在嗜酸性粒细胞上表达,但在正常小鼠的干细胞、树突状细胞或胸腺、淋巴结或脾脏的细胞上不表达。与人类Th2细胞不同,小鼠Th2细胞不表达可检测水平的CCR3,对嗜酸性粒细胞趋化因子也没有可测量的反应。这些单克隆抗体均不是CCR3钙动员的拮抗剂或激动剂。据我们所知,本文所述的抗体是首批报道的对小鼠嗜酸性粒细胞具有特异性且易于用于嗜酸性粒细胞检测、分离和体内清除的单克隆抗体。

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