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hCD47诱导人巨噬细胞对猪内皮细胞的免疫耐受

胡文宝 潘登科 David K.C.Cooper 蔡志明 牟丽莎

胡文宝, 潘登科, David K.C.Cooper, 等. hCD47诱导人巨噬细胞对猪内皮细胞的免疫耐受[J]. 器官移植, 2019, 10(2): 165-170. doi: 10.3969/j.issn.1674-7445.2019.02.008
引用本文: 胡文宝, 潘登科, David K.C.Cooper, 等. hCD47诱导人巨噬细胞对猪内皮细胞的免疫耐受[J]. 器官移植, 2019, 10(2): 165-170. doi: 10.3969/j.issn.1674-7445.2019.02.008
Hu Wenbao, Pan Dengke, David K.C.Cooper, et al. hCD47 induces immune tolerance of human macrophages to porcine endothelial cells[J]. ORGAN TRANSPLANTATION, 2019, 10(2): 165-170. doi: 10.3969/j.issn.1674-7445.2019.02.008
Citation: Hu Wenbao, Pan Dengke, David K.C.Cooper, et al. hCD47 induces immune tolerance of human macrophages to porcine endothelial cells[J]. ORGAN TRANSPLANTATION, 2019, 10(2): 165-170. doi: 10.3969/j.issn.1674-7445.2019.02.008

hCD47诱导人巨噬细胞对猪内皮细胞的免疫耐受

doi: 10.3969/j.issn.1674-7445.2019.02.008
基金项目: 

国家自然科学基金青年项目 31700680

国家重点研发计划 2017YFC1103704

中国博士后科学基金 2016M602571

深圳市医疗卫生三名工程 SZSM201412020

深圳市科技计划 JCJY20160229204849975

深圳市科技计划 GJHZ20170314171357556

详细信息
    作者简介:

    胡文宝,男,1983年生,博士后,研究方向为移植免疫,Email:wenbaohu2016@gmail.com

    通讯作者:

    牟丽莎,女,1983年生,副研究员,研究方向为异种移植,Email: lishamou@gmail.com

  • 中图分类号: R617, R392.4

hCD47 induces immune tolerance of human macrophages to porcine endothelial cells

More Information
  • 摘要:   目的  探讨人CD47(hCD47)在诱导人巨噬细胞对猪内皮细胞免疫耐受中的作用。  方法  将转染了pCDH-hCD47-FLAG质粒的猪髂总动脉内皮细胞(PIEC)设为pCDH-hCD47组;将转染了pCDH-FLAG空载体质粒的PIEC为pCDH组;将转染了hCD47-dN的PIEC设为pCDH-hCD47-dN组;将人脐静脉内皮细胞(HUVEC)设为阳性对照组。将细胞分别与人巨噬细胞共培养,检测信号调节蛋白α(SIRPα)的磷酸化情况以及人巨噬细胞对PIEC的杀伤作用。进一步从GT-/-及GT-/-/hCD47基因编辑猪中分离了猪主动脉血管内皮细胞(PAEC), 并分析SIRPα的磷酸化情况及人巨噬细胞对PAEC的杀伤作用。  结果  pCDH组细胞不能诱导SIRPα的磷酸化,而pCDH-hCD47组细胞与人巨噬细胞共培养10 min后便能够激活SIRPα的磷酸化,且随着共培养时间的延长,SIRPα的磷酸化程度也随之增强。pCDH-hCD47-dN组细胞不能激活SIRPα的磷酸化。人巨噬细胞对pCDH组细胞产生了明显的杀伤作用,pCDH-hCD47组细胞可明显抑制人巨噬细胞的杀伤作用(P < 0.05),而pCDH-hCD47-dN组细胞则不能抑制人巨噬细胞的杀伤作用。GT-/--PAEC与人巨噬细胞共培养后,不能激活SIRPα的磷酸化;而GT-/-/hCD47-PAEC与人巨噬细胞共培养后则明显激活了SIRPα的磷酸化。人巨噬细胞对GT-/--PAEC产生了明显的杀伤作用,GT-/-/hCD47-PAEC可明显抑制人巨噬细胞的杀伤作用(P < 0.05)。  结论  在猪内皮细胞中表达hCD47可以通过激活SIRPα的磷酸化抑制人巨噬细胞对内皮细胞的杀伤作用。

     

  • 图  1  各组细胞与人巨噬细胞共培养后对SIRP α磷酸化的影响

    A图为pCDH-hCD47组、pCDH组和阳性对照组细胞分别与人巨噬细胞共培养0、10、20、30 min;B图为pCDH-hCD47-dN组、pCDH-hCD47组和pCDH组细胞与人巨噬细胞共培养30 min

    Figure  1.  Effect on SIRP α phosphorylation after co-culture of human macrophages and cells in each group

    图  2  人巨噬细胞对各组PIEC的杀伤作用

    Figure  2.  The killing effect of human macrophages on PIEC in each group

    图  3  PAEC与人巨噬细胞共培养后对SIRP α磷酸化的影响

    Figure  3.  Effect on SIRP α phosphorylation afterco-culture of PAEC and human macrophages

    图  4  人巨噬细胞对PAEC的杀伤作用

    Figure  4.  The killing effect of human macrophages on PAEC

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出版历程
  • 收稿日期:  2018-12-20
  • 网络出版日期:  2021-01-19
  • 刊出日期:  2019-03-15

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