McKenzie S E, Taylor S M, Malladi P, Yuhan H, Cassel D L, Chien P, Schwartz E, Schreiber A D, Surrey S, Reilly M P
Department of Pediatrics, Jefferson Medical College, Philadelphia, PA 19107, USA.
J Immunol. 1999 Apr 1;162(7):4311-8.
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.
在人类中，IgG的Fc受体FcγRIIA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起重要作用。小鼠缺乏与人类FcγRIIA基因等同的基因。为了更好地理解FcγRIIA在体内的作用，制备并鉴定了FcγRIIA转基因小鼠。一个转基因小鼠品系在血小板和巨噬细胞上表达的FcγRIIA水平与人细胞相当，在这些血小板上交联FcγRIIA可诱导血小板聚集。使用静脉内和腹腔内注射抗小鼠血小板抗体研究了该转基因品系中的免疫介导的血小板减少症。与FcγRIIA转基因阴性的匹配野生型同窝小鼠相比，FcγRIIA转基因小鼠中抗体介导的血小板减少症明显更严重。相反，在脾巨噬细胞上缺乏Fc受体FcγRI和FcγRIII功能性表达的FcRγ链敲除小鼠未表现出抗体介导的血小板减少症。我们制备了FcγRIIA转基因×FcRγ链敲除小鼠，以研究在缺乏功能性FcγRI和FcγRIII的情况下FcγRIIA在免疫清除中的作用。在FcγRIIA转基因×FcRγ链敲除小鼠中，观察到由FcγRIIA介导的严重免疫性血小板减少症。这些结果表明，FcγRIIA在体内表达或发挥功能不需要FcRγ链。此外，综合来看，数据表明人类Fc受体FcγRIIA在体内血小板的免疫清除中起重要作用。
