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Blood:ADAP缺陷可影响巨核细胞极化、促进血小板前体异位释放,从而导致微血小板减少症

2018-07-02 MedSci MedSci原创

中心点:小鼠ADAP缺陷可导致血小板寿命缩短和异位释放,进而导致微血小板减少。巨核细胞缺乏ADAP会损坏DMS极化和伪足小体形成。摘要:骨髓巨核细胞(MKs)通过将血小板前体延伸到窦状血管产生血小板。血小板生成缺陷可导致血小板减少症,增加出血倾向。近期,有报道称先天性常染色体隐性小血小板减少症(CARST)是由ADAP(黏附和脱颗粒促进调节蛋白,又名FYB、SLAP130/120)基因突变导致的,

中心点:

小鼠ADAP缺陷可导致血小板寿命缩短和异位释放,进而导致微血小板减少。

巨核细胞缺乏ADAP会损坏DMS极化和伪足小体形成。

摘要:

骨髓巨核细胞(MKs)通过将血小板前体延伸到窦状血管产生血小板。血小板生成缺陷可导致血小板减少症,增加出血倾向。近期,有报道称先天性常染色体隐性小血小板减少症(CARST)是由ADAP(黏附和脱颗粒促进调节蛋白,又名FYB、SLAP130/120)基因突变导致的,其特点是微血小板减少和出血症状。

在本研究中,Markus Spindler等人利用ADAP缺陷小鼠(Adap-/-)模型来研究CARST微血小板减少的潜在机制。Adap-/-小鼠表现出人CARST的多个病征,包括中度血小板减少和血小板缩小。与对照组相比,Adap-/-血小板寿命缩短;而且,巨噬细胞耗竭可恢复突变小鼠的血小板计数水平,但脾切除无此效果。

全胸骨3D共聚焦成像和活体双光子显微镜显示ADAP缺陷型MKs的形态发生改变,表现为分裂和血小板(前体)样微粒异位释放至骨髓室。此外,在体外培养的骨髓来源的MKs缺乏ADAP时细胞外基质蛋白扩张减少、β1整合蛋白激活进而破坏伪足小体形成,表现为膜分界系统极化障碍。

MK-/血小板特异性ADAP缺陷小鼠(PF4-cre)也表现为血小板生成减少、血小板体积缩小和血小板异位释放。

本研究结果表明突变小鼠血小板生成异常是由巨核细胞内在缺陷导致,提示ADAP在MK极化和血小板的生物合成过程中发挥重要作用。

原始出处:

Markus Spindler,et al.ADAP deficiency impairs megakaryocyte polarization with ectopic proplatelet release and causes microthrombocytopenia. Blood  2018  :blood-2018-01-829259;  doi: https://doi.org/10.1182/blood-2018-01-829259

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    2019-04-25 kalseyzl
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    2018-07-04 般若傻瓜
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  7. [GetPortalCommentsPageByObjectIdResponse(id=1811930, encodeId=ce7d1811930f3, content=<a href='/topic/show?id=98838902198' target=_blank style='color:#2F92EE;'>#血小板前体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89021, encryptionId=98838902198, topicName=血小板前体)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2726119, createdName=july_975, createdTime=Sat Dec 15 21:08:00 CST 2018, time=2018-12-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1779024, encodeId=8e6a1e79024b1, content=<a href='/topic/show?id=5e05194410' target=_blank style='color:#2F92EE;'>#ADAP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1944, encryptionId=5e05194410, topicName=ADAP)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c77e138, createdName=kalseyzl, createdTime=Thu Apr 25 23:08:00 CST 2019, time=2019-04-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1264656, encodeId=5515126465676, content=<a href='/topic/show?id=150f19229c' target=_blank style='color:#2F92EE;'>#ADA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1922, encryptionId=150f19229c, topicName=ADA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ad9f79, createdName=般若傻瓜, createdTime=Wed Jul 04 02:08:00 CST 2018, time=2018-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1302791, encodeId=2ed91302e9194, content=<a href='/topic/show?id=9c72890153c' target=_blank style='color:#2F92EE;'>#血小板减少#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89015, encryptionId=9c72890153c, topicName=血小板减少)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Wed Jul 04 02:08:00 CST 2018, time=2018-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1490273, encodeId=042f14902e3d2, content=<a href='/topic/show?id=af9f48201a9' target=_blank style='color:#2F92EE;'>#巨核细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=48201, encryptionId=af9f48201a9, topicName=巨核细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f3d78715376, createdName=liuquan, createdTime=Wed Jul 04 02:08:00 CST 2018, time=2018-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1597876, encodeId=7266159e8765b, content=<a href='/topic/show?id=b1e3e7926ba' target=_blank style='color:#2F92EE;'>#细胞极化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77926, encryptionId=b1e3e7926ba, topicName=细胞极化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d3e318558301, createdName=tastas, createdTime=Wed Jul 04 02:08:00 CST 2018, time=2018-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=328716, encodeId=1ade328e1646, content=谢谢分享学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=114, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Mon Jul 02 12:09:17 CST 2018, time=2018-07-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=328707, encodeId=8d26328e0795, content=了解一下.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Mon Jul 02 11:45:04 CST 2018, time=2018-07-02, status=1, ipAttribution=)]
    2018-07-02 清风拂面

    谢谢分享学习

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1811930, encodeId=ce7d1811930f3, content=<a href='/topic/show?id=98838902198' target=_blank style='color:#2F92EE;'>#血小板前体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89021, encryptionId=98838902198, topicName=血小板前体)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2726119, createdName=july_975, createdTime=Sat Dec 15 21:08:00 CST 2018, time=2018-12-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1779024, encodeId=8e6a1e79024b1, content=<a href='/topic/show?id=5e05194410' target=_blank style='color:#2F92EE;'>#ADAP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1944, encryptionId=5e05194410, topicName=ADAP)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c77e138, createdName=kalseyzl, createdTime=Thu Apr 25 23:08:00 CST 2019, time=2019-04-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1264656, encodeId=5515126465676, content=<a href='/topic/show?id=150f19229c' target=_blank style='color:#2F92EE;'>#ADA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1922, encryptionId=150f19229c, topicName=ADA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ad9f79, createdName=般若傻瓜, createdTime=Wed Jul 04 02:08:00 CST 2018, time=2018-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1302791, encodeId=2ed91302e9194, content=<a href='/topic/show?id=9c72890153c' target=_blank style='color:#2F92EE;'>#血小板减少#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89015, encryptionId=9c72890153c, topicName=血小板减少)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Wed Jul 04 02:08:00 CST 2018, time=2018-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1490273, encodeId=042f14902e3d2, content=<a href='/topic/show?id=af9f48201a9' target=_blank style='color:#2F92EE;'>#巨核细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=48201, encryptionId=af9f48201a9, topicName=巨核细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f3d78715376, createdName=liuquan, createdTime=Wed Jul 04 02:08:00 CST 2018, time=2018-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1597876, encodeId=7266159e8765b, content=<a href='/topic/show?id=b1e3e7926ba' target=_blank style='color:#2F92EE;'>#细胞极化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77926, encryptionId=b1e3e7926ba, topicName=细胞极化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d3e318558301, createdName=tastas, createdTime=Wed Jul 04 02:08:00 CST 2018, time=2018-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=328716, encodeId=1ade328e1646, content=谢谢分享学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=114, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Mon Jul 02 12:09:17 CST 2018, time=2018-07-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=328707, encodeId=8d26328e0795, content=了解一下.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Mon Jul 02 11:45:04 CST 2018, time=2018-07-02, status=1, ipAttribution=)]
    2018-07-02 天地飞扬

    了解一下.谢谢分享!

    0

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