Rapid remodeling of tight junctions during paracellular diapedesis in a human model of the blood-brain barrier.
Rapid remodeling of tight junctions during paracellular diapedesis in a human model of the blood-brain barrier.
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DOI：
10.4049/jimmunol.1400700
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发表时间：
2014-09-01
期刊：
影响因子：
--
通讯作者：
Muller WA
中科院分区：
文献类型：
--
作者：
Winger RC;Koblinski JE;Kanda T;Ransohoff RM;Muller WA
白细胞跨内皮迁移（TEM；渗出）是免疫监视和炎症的关键事件。大多数透射电镜发生在内皮细胞边界（细胞旁）。然而，有间接证据表明，在血脑屏障（BBB）的紧密连接处，白细胞直接通过内皮细胞体（跨细胞）迁移。为什么白细胞通过内皮细胞体而不是细胞边界迁移尚不清楚。为了验证内皮细胞连接的紧密性影响血流途径的假设，我们开发了一个体外血脑屏障模型，该模型具有比标准培养条件高10倍的电阻，并强烈表达血脑屏障紧密连接蛋白claudin-5和claudin-3。我们发现细胞旁TEM仍然是主要的途径（≥98%），并且TEM依赖于PECAM-1和CD99。我们发现表达claudin-5的内皮紧密连接是动态的，并且在TEM中经历快速重塑。来自内皮侧边界再循环室（LBRC）的膜被动员到紧密连接重构的确切位置。这通过用膜密封细胞间隙，并在迁移的白细胞穿过细胞边界时与未结连的粘附分子（PECAM-1和CD99）接合，从而保护了内皮屏障。这些发现为血脑屏障中白细胞-内皮相互作用提供了新的见解，并表明紧密连接比以前所认识的更具动态性。
Leukocyte transendothelial migration (TEM; diapedesis) is a critical event in immune surveillance and inflammation. Most TEM occurs at endothelial cell borders (paracellular). However, there is indirect evidence to suggest that at the tight junctions of the blood-brain barrier (BBB), leukocytes migrate directly through the endothelial cell body (transcellular). Why leukocytes migrate through the endothelial cell body rather than the cell borders is unknown. To test the hypothesis that the tightness of endothelial cell junctions influences the pathway of diapedesis, we developed an in vitro model of the BBB that possessed ten-fold higher electrical resistance than standard culture conditions and strongly expressed the BBB tight junction proteins claudin-5 and claudin-3. We found that paracellular TEM was still the predominant pathway (≥98%) and TEM was dependent on PECAM-1 and CD99. We show that endothelial tight junctions expressing claudin-5 are dynamic and undergo rapid remodeling during TEM. Membrane from the endothelial lateral border recycling compartment (LBRC) is mobilized to the exact site of tight junction remodeling. This preserves the endothelial barrier by sealing the intercellular gaps with membrane and engaging the migrating leukocyte with unligated adhesion molecules (PECAM-1 and CD99) as it crosses the cell border. These findings provide new insights into leukocyte-endothelial interactions at the BBB and suggest that tight junctions are more dynamic than previously appreciated.
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影响因子：
4
作者：
Dejana, Elisabetta;Orsenigo, Fabrizio;Lampugnani, Maria Grazia
通讯作者：
Lampugnani, Maria Grazia
DOI：
10.1083/jcb.148.1.203
发表时间：
2000-01-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Allport JR;Muller WA;Luscinskas FW
通讯作者：
Luscinskas FW
DOI：
10.1212/01.con.0000389940.92283.aa
发表时间：
2010-10-01
期刊：
Continuum (Minneapolis, Minn.)
影响因子：
--
作者：
Awad, Amer M;Stuve, Olaf
通讯作者：
Stuve, Olaf
影响因子：
2.9
作者：
BUTT, AM
通讯作者：
BUTT, AM
影响因子：
--
作者：
Dufour EM;Deroche A;Bae Y;Muller WA
通讯作者：
Muller WA