ESAM supports neutrophil extravasation, activation of Rho, and VEGF-induced vascular permeability.
ESAM supports neutrophil extravasation, activation of Rho, and VEGF-induced vascular permeability.
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DOI：
10.1084/jem.20060565
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发表时间：
2006-07-10
期刊：
影响因子：
--
通讯作者：
Vestweber D
中科院分区：
文献类型：
--
作者：
Wegmann F;Petri B;Khandoga AG;Moser C;Khandoga A;Volkery S;Li H;Nasdala I;Brandau O;Fässler R;Butz S;Krombach F;Vestweber D
内皮细胞选择性粘附分子 (ESAM) 在内皮紧密连接和血小板上特异性表达。为了测试 ESAM 是否参与白细胞外渗，我们培育了携带 ESAM 基因破坏的小鼠，并在三种不同的炎症模型中对它们进行了分析。我们发现淋巴细胞募集到发炎皮肤中并未受到基因破坏的影响。然而，刺激后 2 小时，中性粒细胞向化学性发炎腹膜的迁移被抑制 70%，并在随后的时间点恢复。通过活体显微镜直接分析提睾肌中的中性粒细胞外渗表明，ESAM−/− 小鼠的白细胞外渗减少了 (50%)，且不影响白细胞滚动和粘附。消耗 >98% 的循环血小板并不能消除 ESAM 缺乏相关的对中性粒细胞外渗的抑制作用，表明只有内皮紧密连接处的 ESAM 与外渗过程相关。降低内皮细胞中 ESAM 的表达会导致活化的 Rho 水平降低，Rho 是一种与紧密连接不稳定有关的 GTP 酶。事实上，ESAM−/− 小鼠中血管内皮生长因子刺激的血管通透性降低。总的来说，内皮紧密连接处的 ESAM 可能通过影响内皮细胞接触参与中性粒细胞穿过血管壁的迁移。
Endothelial cell–selective adhesion molecule (ESAM) is specifically expressed at endothelial tight junctions and on platelets. To test whether ESAM is involved in leukocyte extravasation, we have generated mice carrying a disrupted ESAM gene and analyzed them in three different inflammation models. We found that recruitment of lymphocytes into inflamed skin was unaffected by the gene disruption. However, the migration of neutrophils into chemically inflamed peritoneum was inhibited by 70% at 2 h after stimulation, recovering at later time points. Analyzing neutrophil extravasation directly by intravital microscopy in the cremaster muscle revealed that leukocyte extravasation was reduced (50%) in ESAM−/− mice without affecting leukocyte rolling and adhesion. Depletion of >98% of circulating platelets did not abolish the ESAM deficiency–related inhibitory effect on neutrophil extravasation, indicating that it is only ESAM at endothelial tight junctions that is relevant for the extravasation process. Knocking down ESAM expression in endothelial cells resulted in reduced levels of activated Rho, a GTPase implicated in the destabilization of tight junctions. Indeed, vascular permeability stimulated by vascular endothelial growth factor was reduced in ESAM−/− mice. Collectively, ESAM at endothelial tight junctions participates in the migration of neutrophils through the vessel wall, possibly by influencing endothelial cell contacts.
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DOI：
10.1084/jem.184.1.229
发表时间：
1996-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Wakelin MW;Sanz MJ;Dewar A;Albelda SM;Larkin SW;Boughton-Smith N;Williams TJ;Nourshargh S
通讯作者：
Nourshargh S
影响因子：
4.8
作者：
Hirata, K;Ishida, T;Quertermous, T
通讯作者：
Quertermous, T
影响因子：
3.7
作者：
Wegmann, F;Ebnet, K;Butz, S
通讯作者：
Butz, S
影响因子：
3.5
作者：
Strey, A;Janning, A;Gerke, V
通讯作者：
Gerke, V
影响因子：
4
作者：
Ebnet, K;Aurrand-Lions, M;Vestweber, D
通讯作者：
Vestweber, D