Targeted recycling of PECAM from endothelial surface-connected compartments during diapedesis
Targeted recycling of PECAM from endothelial surface-connected compartments during diapedesis
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DOI：
10.1038/nature01300
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发表时间：
2003-02-13
期刊：
影响因子：
64.8
通讯作者：
Muller, WA
中科院分区：
文献类型：
--
作者：
Mamdouh, Z;Chen, X;Muller, WA
白细胞通过毛细血管后小静脉内皮细胞之间的边界挤压进入炎症部位。这个快速的过程被称为跨内皮迁移（TEM）或浸润，在白细胞停留在内皮表面后90秒内完成（1-4）。在这段时间里，白细胞以变形虫的方式穿过内皮细胞边界，在运输过程中，内皮细胞仍然紧紧地与它相对立。目前尚不清楚内皮细胞如何迅速和可逆地改变其边界以适应迁移的白细胞。在这里，我们展示了在细胞边界的质膜下方有一个膜网络，它间隔连接到连接表面。PECAM-1是一种完整的膜蛋白，在TEM5-7中起重要作用，存在于这个隔室中，并沿着内皮细胞边界均匀地循环。然而，在TEM过程中，回收PECAM的目标是单核细胞正在迁移的连接段。此外，用PECAM抗体阻断TEM特异性阻断该膜向白细胞迁移区域的募集，而不影响构成膜的运输。
Leukocytes enter sites of inflammation by squeezing through the borders between endothelial cells that line postcapillary venules at that site. This rapid process, called transendothelial migration (TEM) or diapedesis, is completed within 90 s after a leukocyte arrests on the endothelial surface(1-4). In this time, the leukocyte moves in ameboid fashion across the endothelial borders, which remain tightly apposed to it during transit. It is not known how the endothelial cell changes its borders rapidly and reversibly to accommodate the migrating leukocyte. Here we show that there is a membrane network just below the plasmalemma at the cell borders that is connected at intervals to the junctional surface. PECAM-1, an integral membrane protein with an essential role in TEM5-7, is found in this compartment and constitutively recycles evenly along endothelial cell borders. During TEM, however, recycling PECAM is targeted to segments of the junction across which monocytes are in the act of migration. In addition, blockade of TEM with antibodies against PECAM specifically blocks the recruitment of this membrane to the zones of leukocyte migration, without affecting the constitutive membrane trafficking.