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CD36单克隆抗体体内清除血小板的机制探讨

The Study on the Mechanism of Platelet Clearance Caused by Anti-CD36 Monoclonal Antibodies in Vivo

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【作者】 徐秀章陈大伟夏文杰邓晶陈扬凯丁浩强刘静叶欣

【Author】 XU Xiuzhang;CHEN Dawei;XIA Wenjie;DENG Jing;CHEN Yangkai;DING Haoqiang;LIU Jing;YE Xin;The Key Medical Laboratory of Guangzhou,Guangzhou Blood Center;

【通讯作者】 叶欣;

【机构】 广州市血液安全重点实验室

【摘要】 目的 探讨CD36抗体在体内介导血小板吞噬清除的作用机制。方法 将单克隆抗体(mAb)32-106(IgG2a)以2 mg/kg的浓度注射给C57BL/6J雌鼠,并分别在注射前0 h、注射后0.5 h、1 h、2 h、4 h、6 h及24 h检测小鼠体内血小板数量,通过胃蛋白酶消化处理,获得32-106的F(ab’)2段,并将其注射给C57BL/6J雌鼠,分析其清除CD36(+)血小板的效果,制备其他亚型的32-106,通过体内实验分析其对CD36(+)血小板的清除作用。结果 体内实验证实,mAb 32-106 IgG2a可导致C57BL/6J雌鼠体内血小板数的明显降低(P<0.05),而mAb 32-106的F(ab’)2段并不引起雌鼠体内血小板的减少。C57BL/6J雌鼠接受2 mg/kg的32-106 IgG1或32-106 IgG3,也发生血小板数量降低,但与32-106 IgG2a相比,IgG1及IgG3亚型32-106引起的小鼠血小板减少不明显。结论 通过体内实验证实,CD36抗体以Fc依赖途径参与体内CD36(+)血小板的清除,且IgG2a亚型的抗体引起的血小板清除效果显著。

【Abstract】 Objective To study the mechanism of platelet clearance caused by anti-CD36 antibodies in vivo.Methods The monoclonal antibody (mAb) 32-106 (IgG2a) was injected into the C57BL/6J female mice at a concentration of 2 mg/kg,and the platelet counts of these mice were detected at 0 h before injection,0.5 h,1 h,2 h,4 h,6 h and 24 h after injection.The F (ab’) 2 segment of 32-106 was obtained by digestion with pepsin and then injected into the C57BL/6J mice to analyze its clearance effect on CD36 (+) platelets.Subsequently,other subclasses of mAb 32-106 were generated and injected into the mice to analyze its clearance effect on CD36 (+) platelets.Results mAb 32-106 IgG2a significantly decreased the number of CD36 (+) platelets in C57BL/6J female mice (P<0.05) in vivo.However,the F (ab’) 2 segment of mAb 32-106 did not cause platelet clearance in female mice.The C57BL/6J female mice receiving 2 mg/kg of 32-106 IgG1 or 32-106 IgG3 also experienced decreased platelet counts.Compared with 32-106 IgG2a,the thrombocytopenia induced by 32-106 IgG3 or 32-106 IgG1 was not significant in mice.Conclusion The clearance of CD36 (+) platelets caused by anti-CD36 antibodies in vivo is in an Fc-dependent pathway,and anti-CD36 IgG2a antibody has a significant effect on CD36 (+) platelet clearance.

【关键词】 CD36单克隆抗体血小板清除Fc依赖
【Key words】 CD36Monoclonal antibodyPlatelet clearanceFc-dependent
【基金】 广东省自然科学基金(No.2024A1515012652);广州市科技计划项目(No.202201011749、No.2024A03J0375、No.2023A03J0549、No.2023A03J0552、No.202201010013、No.2023A03J0997、No.2025A03J3369)资助
  • 【文献出处】 临床输血与检验 ,Journal of Clinical Transfusion and Laboratory Medicine , 编辑部邮箱 ,2025年01期
  • 【分类号】R457.1
  • 【下载频次】45
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