The role of the human Fc receptor Fc gamma RIIA in the immune clearance of platelets: a transgenic mouse model.
The role of the human Fc receptor Fc gamma RIIA in the immune clearance of platelets: a transgenic mouse model.
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DOI：
10.4049/jimmunol.162.7.4311
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发表时间：
1999-04
影响因子：
4.4
通讯作者：
S. Mckenzie;Scott M. Taylor;P. Malladi;Heena Yuhan;Cassel Dl;P. Chien;E. Schwartz;A. Schreiber-
中科院分区：
文献类型：
--
作者：
S. Mckenzie;Scott M. Taylor;P. Malladi;Heena Yuhan;Cassel Dl;P. Chien;E. Schwartz;A. Schreiber-
在人类中，IgG 的 Fc 受体 FcgammaRIIA 在巨噬细胞和血小板上表达，可能在免疫介导的血小板减少症的病理生理学中发挥重要作用。小鼠缺乏与人类 FcgammaRIIA 相当的基因。为了更好地了解 FcgammaRIIA 在体内的作用，生成并表征了 FcgammaRIIA 转基因小鼠。一种转基因小鼠系在血小板和巨噬细胞上表达 FcgammaRIIA，其水平与人类细胞相当，并且这些血小板上的 FcgammaRIIA 交联诱导血小板聚集。使用静脉注射研究了该转基因系中免疫介导的血小板减少症。和IP。施用抗小鼠血小板抗体。与 FcgammaRIIA 转基因阴性的匹配野生型同窝小鼠相比，FcgammaRIIA 转基因小鼠中 Ab 介导的血小板减少症明显更严重。相比之下，脾巨噬细胞上缺乏 Fc 受体 FcgammaRI 和 FcgammaRIII 功能性表达的 FcR γ 链敲除小鼠并未表现出 Ab 介导的血小板减少症。我们生成了 FcgammaRIIA 转基因 x FcR γ 链敲除小鼠，以检查在功能性 FcgammaRI 和 FcgammaRIII 缺失的情况下 FcgammaRIIA 在免疫清除中的作用。在 FcgammaRIIA 转基因 x FcR γ 链敲除小鼠中，观察到由 FcgammaRIIA 介导的严重免疫性血小板减少症。这些结果证明 FcgammaRIIA 不需要 FcR γ 链来在体内表达或发挥功能。此外，综合起来，数据表明人Fc受体FcgammaRIIA在体内血小板的免疫清除中发挥重要作用。
In humans, the Fc receptor for IgG, FcgammaRIIA, is expressed on macrophages and platelets and may play an important role in the pathophysiology of immune-mediated thrombocytopenia. Mice lack the genetic equivalent of human FcgammaRIIA. To better understand the role of FcgammaRIIA in vivo, FcgammaRIIA transgenic mice were generated and characterized. One transgenic mouse line expressed FcgammaRIIA on platelets and macrophages at levels equivalent to human cells, and cross-linking FcgammaRIIA on these platelets induced platelet aggregation. Immune-mediated thrombocytopenia in this transgenic line was studied using i.v. and i.p. administration of anti-mouse platelet Ab. In comparison with matched wild-type littermates that are negative for the FcgammaRIIA transgene, Ab-mediated thrombocytopenia was significantly more severe in the FcgammaRIIA transgenic mice. In contrast, FcR gamma-chain knockout mice that lack functional expression of the Fc receptors FcgammaRI and FcgammaRIII on splenic macrophages did not demonstrate Ab-mediated thrombocytopenia. We generated FcgammaRIIA transgenic x FcR gamma-chain knockout mice to examine the role of FcgammaRIIA in immune clearance in the absence of functional FcgammaRI and FcgammaRIII. In FcgammaRIIA transgenic x FcR gamma-chain knockout mice, severe immune thrombocytopenia mediated by FcgammaRIIA was observed. These results demonstrate that FcgammaRIIA does not require the FcR gamma-chain for expression or function in vivo. Furthermore, taken together, the data suggest that the human Fc receptor FcgammaRIIA plays a significant role in the immune clearance of platelets in vivo.