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新品发布|CD31—多功能分子

武汉华美生物工程有限公司2019年12月30日 11:28 点击:216

KANGYUAN,YOUCHENGWEIXUEXIAOBANNEIPIXIBAONIANFUFENZI(PECAM-1),SHIXIANGDUIFENZIZHILIANGWEI130kDa DEI XINGKUAMOTANGDANBAI,SHUYUMIANYIQIUDANBAICHAOJIAZUCHENGYUAN,KEZAINEIPIXIBAO、XUNHUANDEXUEXIAOBAN、DANHEXIBAO、ZHONGXINGXIBAOJITXIBAOYAQUNBIAOMIANBIAODA。ZAI2015NIANASCOHUIYISHANG,Michael J. Birrer, MDTUANDUIJIEHETAMENDEYANJIUTICHUCD31SHILUANCHAOAIZHONGBEIFADANKANGLIAOXIAODEQIANZAIBIAOZHIWU。YINWEIBEIFADANKANGDUIWUJINZHANSHENGCUNQIHEZONGSHENGCUNQIDEYINGXIANGZAIGAOCD31DEHUANZHEZHONGZUIWEIMINGXIAN。ZHEIYIFAXIANZAICIYINQILEGUONEIWAIXUEZHEDUICD31DEGUANZHU。BENWENJIUCD31DEDINGYI、JIEGOU、GONGSHOUTI、GONGNENG、XINHAOTONGLUJIXIANGGUANJIBINGJINXINGJIANDANJIESHAO。

1. 什么是CD31?

2. CD31的结构

3. CD31的共受体

4. CD31的功能

5. CD31信号传导

6. CD31相关疾病

1. 什么是CD31?

CD31是是由位于17号染色体长臂末端的75kb基因编码的跨膜糖蛋白。CD31最早是Newman及其同事于1990年发表于Science上的一篇报告中提出。该文通过血小板整膜糖蛋白抗体结合实验发现了新的免疫球蛋白超家族细胞粘附分子(cell adhesion molecule,CAM)成员即是曾经确定为CD31的粒一单核细胞分化抗原[1] [2] [3]

XIBAOZHANFUFENZI(CAM)SHICANYUXIBAOYUXIBAOZHIJIANJIXIBAOYUXIBAOWAIJIZHIZHIJIANXIANGHUZUOYONGDEFENZI。KEDAZHIFENWEIWULEI:GAIZHANSU(cadherin)、XUANZESU(selectin)、MIANYIQIUDANBAICHAOJIAZU(IgSF)、ZHENGHESU(integrin)JITOUMINGZHISUANZHANSU(hyaladherin)。MIANYIQIUDANBAICHAOJIAZUZHONGDEXIBAOZHANFUFENZIHAIYOUGEZHONGSHENJINGXIBAOZHANFUFENZI(N-CAM),XIBAOWENZHANFUFENZI(I-CAM)JIMAIGUANXIBAOZHANFUFENZI(V-CAM)DENG,QIZHONGN-CAMHECD31SHUYUQINTONGXINGCAM(LIANGXIANGLINXIBAOBIAOMIANDETONGZHONGCAMFENZIJIANDEXIANGHUSHIBIEYUJIEHE);I-CAMHEV-CAMSHUYUQINYIXINGCAM(LIANGXIANGLINXIBAOBIAOMIANDEBUTONGZHONGCAMFENZIJIANDEXIANGHUSHIBIEYUJIEHE)。

2. CD31的结构

不用本金就能赚钱的方法CD31SHIFENZILIANGWEI130kDaDEKUAMOTANGDANBAI。YOUYUTANGJIHUACHAYIZAIBUTONGXIBAOLEIXINGZHONGFENZIYOUXIEXUBUTONG。RENDECD31DANBAIBAOHANSANGEJIEGOUYU,FENBIESHIBAOWAIJIEGOUYU,KUAMOJIEGOUYUHEBAONEIJIEGOUYU。QIZHONG,BAOWAIJIEGOUYUYOU574GEANJISUANZUCHENG,KUAMOJIEGOUYUBAOHAN19GESHUSHUIANJISUAN,BAONEIJIEGOUYUBAOHAN118GEANJISUAN。GONGNENGQUZHUYAOJIZHONGZAIBAOWAIJIEGOUYUHEBAONEIJIEGOUYU。JIEGOURUTUYISUOSHI:

Schematic Diagram of CD31 Protein

TU1 Schematic Diagram of CD31 Protein

2.1 胞外结构域

CD31DEBAOWAIBUFEN,CHULEXINHAOTAIZHIWAI,SHENGYUDEANJISUANXINGCHENG6GEMIANYIQIUDANBAIYADANWEIZUCHENGDETONGYUANQU,MEIGETONGYUANQUYOUYIGEDANDUDEWAIXIANZIBIANMA,BINGJIEZHUBANGUANGANSUANCANJIXINGCHENGDEERLIUJIANZUCHENGBAOSHOUDEIgC2XINGYADANWEI, MEIGEYADANWEIYUEHAN100GEANJISUANCANJI。

CD31胞外区的第一、二免疫球蛋白样区(IgD1和IgD2)为嗜同种性粘附的结合位点,共同介导嗜同种性粘附,第六免疫球蛋白样区可调节CD31的粘附表型。增加受体与配体之间的第一、二免疫球蛋白样区的亲和力;CD31胞外区的第二免疫球蛋白样区为异嗜性粘附的结合位点,第二免疫球蛋白样区的肝素结合序列可介导异嗜粘附,且依赖于氨基葡聚糖的存在[4]

2.2 胞内结构域

不用本金就能赚钱的方法CD31BAONEIJIEGOUYUDEJIEGOUSHIYOUERWEIHECIGONGZHENQUEDING,HANYOUYOUFEIKONGZHIQUYUGEKAIDELIANGGEZHIZHIXIANGGUANQUYU。CD31JIYINTONGCHANGYOU16EWAIXIANZIZUCHENG(MEIGEWAIXIANZIZHIJIANYOUNEIHANZIGEKAI)。GAIJIEGOUYUYOU8GEWAIXIANZIZUCHENG(RUfigure1SUOSHI)。

CD31BAONEIJIEGOUYUHANYOULIANGGEGONGYOUXULIE,FENBIEXINGCHENGLIANGGEMIANYISHOUTILAOANSUANYIZHIJIXU(ITIM),SHIHANYOUSH2DELAOANSUANLINSUANMEI2(SHP-2)TINGBODETEYIWEIDIAN,ZHEILIANGGETEDINGDELAOANSUANWEIY663HEY686。SHP-2YULINSUANHUADEY663HEY686DEJIEHEYINFAFANKUIYIZHIXINGXINHAOZHUANDAODEFASHENG,CONGERJUYOUDUOZHONGSHENGLIXIAOYING。CD31DEBAONEIQUHANYOU12GESerCANJI,4GEThrCANJI,5GETyrCANJI。ZHEIXIEDOUSHIKEJINXINGLINSUANHUADEWEIDIAN。

通过编码胞浆区的变化性拼接可产生异构的CD31,因为异构的CD31可含有(或无)上述位点的氨基酸残基,所以可产生不同表型的CD31。胞浆区有助于CD31定位于细胞间连接和介导细胞间粘附,去除部分胞浆区可明显改变CD31的结合特性,使得CD31介导的粘附性由异嗜性向同种性转变[5] [6]

3. CD31的共受体

DALIANGYANJIUZHENGSHICD31DEGONGSHOUTIZHIYISHIQIBENSHEN。QINHEZUOYONGLITONGCHANGSHIYOUCD31FENZIDEDIYIHEDIERC2JIEGOUYU(BAOWAIDIYIHEDIERGEIgDJIEGOUYU)JIEDAO。LINGWAI,ZHENGLIANSUDEIgSF/CAMYEKEYIYUCD31JIEHE,MUQIANYIZHENGSHIDECD31GONGSHOUTIZHENGLIANDANBAISHIαvβ3(HUOCD51 / CD61)ZHENGLIANDANBAI。 JINGUANZHENGLIANDANBAIZAITXIBAO,NKXIBAO,FEIDAXIBAOHENEIPISHANGBIAODA,DANTAZUOWEIIgSFPEITIYOUDIANBUXUNCHANG,YINWEISUOYOUQITAICAM / VCAMSHOUTIDOUSHIβ1,β2HUOβ7ZHENGLIANDANBAILEIXING。

4. CD31的功能

CD-31 TONGCHANGWEIYUXUEGUANNEIPIXIBAO、XUEXIAOBAN、JUSHIXIBAOHEkufferXIBAO、LIXIBAO、T/NKXIBAO、LINBAXIBAO、JUHEXIBAO、POGUXIBAO、SHIZHONGXINGLIXIBAO。ZAIMOUXIEZHONGLIUYEFAXIANCD31DEBIAODA,RUSHANGPIYANGXUEGUANNEIPILIU、SHANGPIYANGROULIUYANGXUEGUANNEIPILIU、QITAXUEGUANZHONGLIU、ZUZHIXIBAOXINGEXINGZHONGLIUHEJIANGXIBAO。ZAIXUNHUANXUEXIAOBANHEBAIXIBAOZHONG,CD31ZHUYAOSHITONGGUODIAOJIEQIBAONEIJIEGOUYULINSUANHUASHUNXUERXIANZHIXIBAOHUOHUAFANYING,TONGCHANGSHIZUOWEIYIZHIXINGSHOUTIQIZUOYONG。 LINGWAI,D31YEZAINEIPIXIBAOXIBAOJIANLIANJIECHUGAODUBIAODA,ZUOWEIJIXIECHUANGANQI,BAIXIBAOYUNSHUDEDIAOJIEJIHEWEICHINEIPIXIBAOLIANJIEWANZHENGXINGQIZUOYONG。

不用本金就能赚钱的方法YUCD31XIANGGUANDEDADUOSHUHUOXINGKEGUIYINYUSHITONGXINGCD31-CD31XIANGHUZUOYONG。QIZHONGBAOKUOBAIXIBAOWAISHEN、GUSUIZAOXUEHEXUEGUANFAYU。CD31KEYICUJINGEZHONGBAIXIBAOXIANGGUANZHENGLIANDANBAIYUICAM/VCAM IgSFCHENGYUANDEJIEHE,BINGBANGZHUWAIZHOUXUEBAIXIBAOCHUANGUONEIPIPINGZHANG。CUJINCAM-IgSFJIEHESHIYOUYUBAIXIBAOCD31-NEIPIXIBAOCD31CANYUHOU,β1HEβ2ZHENGLIANDANBAIHUOXINGDEPUBIANSHANGDIAOYINQIDE。

5. CD31信号传导

RU2.2BUFENSUOSHU,BAONEIJIEGOUYUZHONGCUNZAIXUDUOSIANSUAN、SUANSUANHELAOANSUANCANJI。CD31JIEDAODEXINHAOCHUANDAOTONGCHANGSHIYOU702WEISIANSUANDELINSUANHUAYINFA,RANHOUYUZHIMOJIEHESHIFANGITIMDE686WEILAOANSUAN,JINERLINSUANHUASrc-JIAZUJIMEILyn。CIWAI,ITIMDE663WEILAOANSUANHUIJIXUFASHENGSHUNXULINSUANHUA。YIDANITIMDE663WEILAOANSUANWANCHENGLINSUANHUA,CD31HUIMUJISrcTONGYUANXING2JIEGOUYUDANBAI,BIRULAOANSUANLINSUANMEISHP-2。

2010年,Federica M. Marelli-Berg团队的一项研究揭示了T细胞中CD31作用机制。在初始T细胞中,细胞表面CD31表达下调与稳态增殖有关,当胸腺流出减少时,CD31负责维持T细胞库中T细胞含量的稳定。而在记忆T细胞中,CD31调节记忆T细胞的流量,但不影响它们的激活[7]

CD31最显着的特征是在其细胞质结构域中存在两个ITIM。这些ITIM在TCR活性后磷酸化,随后募集蛋白酪氨酸磷酸酶(PTP),例如Src同源性2(SH2),抑制TCR信号传导。如图2所示[8]

CD31 Signaling Pathways in T-lymphocytes

不用本金就能赚钱的方法TU2 CD31 Signaling Pathways in T-lymphocytes

6. CD31相关疾病

CD31KEZAISUOYOUBAIXIBAOZHONGBIAODA,BAOKUOTXIBAO、BXIBAOHESHUTUXIBAO。CD31FUZADESHENGWUXUEGONGNENGZHUYAOYUANYUQIZAIMIANYIHEXUEGUANXITONGZHONGZHANFUHEXINHAOCHUANDAOGONGNENGDEZHENGHE。CD31DEYICHANGBIAODAKEYINFADUOZHONGJIBING,LIRUDONGMAIZHOUYANGYINGHUA、YANZHENGHEXUEYEBINGDENG。

6.1、CD31与动脉粥样硬化

在动脉粥样硬化的过程中,CD31的作用主要表现在对冠状斑块稳定性的影响。在心肌梗塞(MI)病人中,血小板CD31复合物浓度是升高的,而在动物模型中梗死区抗CD31抗体的浓度是下降的[9]。在延迟或失败的溶栓病人中血小板CD31复合物表达是增高的。另外,有研究证实过氧化物酶有抗血管氧化的作用,而CD31则影响酶与内皮的接触,从而起到机械性控制粥样硬化的进程。所以推测CD31基因变异在冠心病的进展中有深远的影响。此外,研究发现心绞痛,急性心肌梗死,心源性休克,猝死等均好发于清晨6时到12时这段时间。这与CD31的水平在夜晚和清晨达高峰有一定时间上的吻合性[10]

6.2 CD31与炎症

大量研究数据表明,在急性腹膜炎、急性肺损伤、心肌缺血再灌注损伤和皮肤炎症模型中,CD31抗体可阻断中性粒细胞和单核细胞的募集。Steren等人报道称,在抗CD31抗体处理的鼠肠系膜静脉中,白细胞位于血管腔面,但不能外渗。其中一些研究也存在分歧,Gza.Rlek等发现,在鼠的急性胰腺炎模型中,大部分粘附、活化和迁移的白细胞都伴有氧自由基的释放,而Murat.Turegun等研究发现,在猎的心肌缺血再滔注损伤模型中.抗CD31抗体不能显著抑制中性粒细胞释放氧自由基[11]

The Diagram of CD31 and Inflammation

TU3 The Diagram of CD31 and Inflammation

在炎症反应中,白细胞与内皮细胞之间的相互作用是关键环节,它使得白细胞进入炎症部位并引起组织损伤。CD31特异地定位于血管内皮细胞腔面侧的浆膜,参与不同类型白细胞外渗的最后步骤。因此CD31在炎症微循环损伤中有重要作用,但作用机制尚未弄清楚,还需进一步研究[12] [13]

6.3 CD31与血液疾病

Karen Ballen[14]等人发现,在再生障碍贫血患者外周血及骨髓中,再障组骨髓及外周血单个核细胞CD31、抗原水平明显低于正常对照组。而且相关分析发现,骨髓、外周血单个核细胞CD31、CD44水平与外周血白细胞数、血红蛋白、血小板,骨髓中粒系比例、红系比例、巨核细胞均呈正相关。这些数据表明粘附分子表达异常可能在再障发病中起一定作用。

根据Gordon等[15]的研究可推测,细胞粘附分子能够提示瞄定位点,从而使初始造血细胞粘附到骨髓基质,并提供调节信号,从而使初始造血细胞从骨髓释放前进一步分化。认为再障三系减少与粘附分子表达缺陷密切相关,是再障造血衰竭的重要因素之一。但其确切作用机制仍需要进一步的探讨。

Reference:

[1] 10hto, H., Maeda, H., et al. Blood. 1985, 66,873-88.

[2] AIbelda, S.M., Oliver, P.D., et al. J. Cell Biol. 1990, 110, 1227-1237.

[3] Horace M. DeLisser, Peter J. Newman, et al不用本金就能赚钱的方法. Molecular and functional aspects of PECAM-I/CD31 [J]. Immunology Today. 1994, 15(10):490-495.

[4] Paddock C, Zhou D, et al. Structural basis for PECAM-1 homophilic binding [J]. Blood. 2016, 127:1052–1061.

[5] Paddock C, Lytle BL, et al. Residues within a lipid-associated segment of the PECAM-1 cytoplasmic domain are susceptible to inducible, sequential phosphorylation [J]. Blood. 2011, 117:6012–6023.

[6] Panida Lertkiatmongkol, Danying Liao, et al. Endothelial functions of platelet/endothelial cell adhesion molecule-1 (CD31) [J]. Vascular biology. 2016, 23(3):253-259.

[7] Manes, T. D., Hoer, S., et al. Kaposis sarcoma-associated herpesvirus K3 and K5 proteins block distinct steps in transendothelial migration of effector memory CD4+ T cells by targeting different endothelial proteins [J]. J. Immunol. 2010, 184, 5186–5192.

[8] Federica M. Marelli-Berg, Marc Clement, et al不用本金就能赚钱的方法. An immunologists guide to CD31 function in T-cells [J]. Journal of Cell Science. 2013, 126: 2343-2352.

[9] Nounhargh S.Krombach F, et al不用本金就能赚钱的方法. The role of JAM-A and PECAM?l in modulating leukocyte infiltration in inflamed and ischemic tissues [J]. J Lonkoc Biol. 2006, 80(4):714—718.

[10] Kalinowska A,Losy J.PECAM-1,a key player in neuro-inflammation[J]. Eur J Neurol. 2006, 13(12):1284-1290.

[11] Dangerfiled J, Larbi KY, et al. PECAM-1(CD31) hemophilic interaction up-regulated α6β1 on transmigrated neutrophils in vivo and play a functional role in the ability of α6 integrins to mediate leukocyte migration through the perivascular basement membrane [J]. J Exp Med. 2002, 196(9): 1201-1211.

[12] Ostermann G, Weber KSC, et al不用本金就能赚钱的方法. JAM-1 is a ligand of the β2 intergrin LFA-1 involved in transendothelial migration of leukocytes [J]. Nature Immunol. 2002, 3(2):151-158.

[13] Schenkel AR, Mamdouh Z, et al. CD99 plays a major role in the migration of monocytes through endothelial junctions [J]. Nature Immunol. 2002, 3(2):143-150.

[14] Karon Ballen, Pamela S, et al不用本金就能赚钱的方法.Effect of ex vivo cytokine treatment on human cord blood engraftment in NODseid mice[J].Br J Haematol. 2001, 108(3):629-640.

[15] Gordon MY, Clark D, et al不用本金就能赚钱的方法. Hemopoietic progenitor cell binging to the stromal microenvironment in vitro [J]. Exp Hematol. 1990, 18(7):837.

  


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