CD99 is essential for leukocyte diapedesis in vivo.

CD99 is essential for leukocyte diapedesis in vivo.
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DOI:
10.1080/15419060802442191
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发表时间:
2008-11
影响因子:
--
通讯作者:
Muller WA
Muller WA
中科院分区:
生物4区
文献类型:
--
作者:
Dufour EM;Deroche A;Bae Y;Muller WA

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将白细胞募集到发炎组织中需要白细胞从血流中迁移穿过局部血管的内皮衬里和基底膜。人CD 99是一种32 kD的高度O-糖基化的细胞表面蛋白,在大多数白细胞上表达。我们最近发现CD 99在白细胞和人内皮细胞接触处表达。人CD 99参与两种细胞类型之间的嗜同性相互作用,并参与体外单核细胞和PMN的跨内皮迁移。为了测试CD 99在体内的作用,我们克隆了小鼠CD 99(muCD 99),在体外表达,并产生了针对它的阻断性单克隆抗体。用muCD 99转染细胞赋予它们以CD 99依赖性嗜同性方式聚集的能力。表达muCD 99的细胞不与表达鼠或人PECAM或人CD 99的细胞结合。在巯基乙酸盐腹膜炎炎症模型中,抗CD 99单克隆抗体在18小时时分别阻断了超过40%和80%的中性粒细胞和单核细胞的募集。显微镜检查显示,这种阻塞发生在小静脉的管腔表面。我们得出结论,CD 99在体内白细胞的迁移中起着重要作用。
Recruitment of leukocytes into inflamed tissue requires migration of leukocytes from the blood stream across the endothelial lining and the basement membrane of the local blood vessels. CD99 in humans is a 32 kD highly O-glycosylated cell surface protein expressed on most leukocytes. We recently found CD99 to be expressed in leukocytes and at human endothelial cell contacts. Human CD99 is involved in homophilic interaction between the two cell types and participates in the transendothelial migration of monocytes and PMN in vitro. To test the role of CD99 in vivo, we cloned murine CD99 (muCD99), expressed it in vitro, and generated a blocking monoclonal antibody against it. We first showed that muCD99 is expressed on mouse leukocytes as well as enriched at the endothelial cell borders. Transfection of cells with muCD99 imparts on them the ability to aggregate in a CD99-dependent homophilic manner. Cells expressing muCD99 did not bind to cells expressing murine or human PECAM or human CD99. In the thioglycollate peritonitis model of inflammation, anti-CD99 monoclonal antibody blocked the recruitment of neutrophils and monocytes by over 40 % and 80%, respectively, at 18 hours. Microscopy showed that this blocking occurred at the luminal surface of venules. We conclude that CD99 plays a major role in the emigration of leukocytes in vivo.
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