P-selectin glycoprotein ligand-1 (PSGL-1) on T helper 1 but not on T helper 2 cells binds to P-selectin and supports migration into inflamed skin

P-selectin glycoprotein ligand-1 (PSGL-1) on T helper 1 but not on T helper 2 cells binds to P-selectin and supports migration into inflamed skin
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DOI:
10.1084/jem.185.3.573
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发表时间:
1997-02-03
影响因子:
15.3
通讯作者:
Vestweber, D
Vestweber, D
中科院分区:
医学1区
文献类型:
--
作者:
Borges, E;Tietz, W;Vestweber, D

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我们最近表明,小鼠Th1细胞而不是Th2细胞被选择性地招募到皮肤延迟型超敏反应(DTH)的炎症部位。这种迁移被针对P-和e -选择素的单克隆抗体(mAb)阻断。本研究表明Th1细胞通过p -选择素糖蛋白配体-1 (PSGL-1)与p -选择素结合。这是唯一的糖蛋白配体,可检测到亲和力分离与p -选择素- ig融合蛋白。通过流式细胞术和细胞粘附实验分析,Th1细胞与p -选择素的结合被针对PSGL-1的抗体完全阻断。同样的抗体部分阻断Th1细胞向皮肤DTH反应的迁移。这种阻断活性,与针对E-selectin的单抗结合,是加性的。虽然PSGL-1在Th2细胞上的表达水平与Th1细胞相似,但它不支持与p -选择素结合。因此,PSGL-1的p选择素结合形式将Th1细胞与Th2细胞区分开来。此外,PSGL-1与Th1细胞进入皮肤炎症区域有关。这是首次证明PSGL-1对小鼠白细胞在体内募集的重要性。
We have shown recently that mouse Th1 cells but not Th2 cells are selectively recruited into inflamed sites of a delayed-type hypersensitivity (DTH) reaction of the skin. This migration was blocked by monoclonal antibodies (mAb) against P- and E-selectin. Here we show that Th1 cells bind to P-selectin via the P-selectin glycoprotein ligand-1 (PSGL-1). This is the only glycoprotein ligand that was detectable by affinity isolation with a P-selectin-Ig fusion protein. Binding of Th1 cells to P-selectin, as analyzed by now cytometry and in cell adhesion assays, was completely blocked by antibodies against PSGL-1. The same antibodies blocked partially the migration of Th1 cells into cutaneous DTH reactions. This blocking activity, in combination with that of a mAb against E-selectin, was additive. PSGL-1 on Th2 cells, although expressed at similar levels as on Th1 cells, did not support binding to P-selectin. Thus, the P-selectin-binding form of PSGL-1 distinguishes Th1 cells from Th2 cells. Furthermore, PSGL-1 is relevant for the entry of Th1 cells into inflamed areas of the skin. This is the first demonstration for the importance of PSGL-1 for mouse leukocyte recruitment in vivo.