Polymorphonuclear leukocyte adhesion triggers the disorganization of endothelial cell-to-cell adherens junctions.
Polymorphonuclear leukocyte adhesion triggers the disorganization of endothelial cell-to-cell adherens junctions.
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DOI：
10.1083/jcb.135.2.497
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发表时间：
1996-10
影响因子：
7.8
通讯作者：
Dejana, E
中科院分区：
文献类型：
--
作者：
DelMaschio, A;Zanetti, A;Corada, M;Rival, Y;Ruco, L;Lampugnani, MG;Dejana, E
多形核白细胞（PMN）浸润到组织中经常伴随着血管通透性的增加。这表明，中性粒细胞的粘附和迁移可能会引发内皮细胞与细胞连接的结构的修改。在本文中，我们发现，使用间接免疫荧光，PMN粘附肿瘤坏死因子激活的内皮细胞（EC）诱导的消失，从内皮细胞与细胞接触的粘附连接（AJ）的组成部分：血管内皮（VE）-钙粘蛋白，α-连环蛋白，β-连环蛋白和斑珠蛋白。VE-钙粘蛋白/连环蛋白复合物的免疫沉淀和Western印迹分析表明，从复合物和总细胞提取物中，β-连环蛋白和斑珠蛋白的量显著减少。相比之下，VE-钙粘蛋白和α-连环蛋白仅部分受到影响。PMN对内皮AJ的破坏不伴有EC收缩或损伤，并且对VE-钙粘蛋白/连环蛋白复合物具有特异性，因为血小板/内皮细胞粘附分子1（PECAM-1）在细胞接触处的分布没有变化。中性粒细胞粘附EC似乎是一个先决条件VE-钙粘蛋白/连环蛋白复合体解体。用抗整合素β 2单克隆抗体阻断PMN粘附可完全抑制这种现象，而任何诱导PMN粘附增加的条件，如加入PMA或抗β 2激活单克隆抗体，均可重现这种现象。对内皮AJ的影响是特定的PMN，因为粘附活化淋巴细胞没有引起类似的变化。高浓度的蛋白酶抑制剂和氧代谢物清除剂不能防止由PMN介导的AJ紊乱。PMN粘附EC伴随着EC通透性的增加。这种作用依赖于中性粒细胞的粘附，不受蛋白酶和氧反应性代谢产物的介导，并且可以通过用EGTA处理EC来再现。最后，免疫组化分析表明，VE-钙粘蛋白分布的影响，PMN粘附到血管壁在体内。这项工作表明，中性粒细胞的粘附可能会触发细胞内信号EC，可能调节VE-钙粘蛋白/连环蛋白复合体的解体。这种作用可增加EC通透性，促进急性炎症反应时PMN的迁移。
Polymorphonuclear leukocytes (PMN) infiltration into tissues is frequently accompanied by increase in vascular permeability. This suggests that PMN adhesion and transmigration could trigger modifications in the architecture of endothelial cell-to-cell junctions. In the present paper, using indirect immunofluorescence, we found that PMN adhesion to tumor necrosis factor-activated endothelial cells (EC) induced the disappearance from endothelial cell-to-cell contacts of adherens junction (AJ) components: vascular endothelial (VE)-cadherin, alpha-catenin, beta-catenin, and plakoglobin. Immunoprecipitation and Western blot analysis of the VE- cadherin/catenin complex showed that the amount of beta-catenin and plakoglobin was markedly reduced from the complex and from total cell extracts. In contrast, VE-cadherin and alpha-catenin were only partially affected. Disorganization of endothelial AJ by PMN was not accompanied by EC retraction or injury and was specific for VE- cadherin/catenin complex, since platelet/endothelial cell adhesion molecule 1 (PECAM-1) distribution at cellular contacts was unchanged. PMN adhesion to EC seems to be a prerequisite for VE-cadherin/catenin complex disorganization. This phenomenon could be fully inhibited by blocking PMN adhesion with an anti-integrin beta 2 mAb, while it could be reproduced by any condition that induced increase of PMN adhesion, such as addition of PMA or an anti-beta 2-activating mAb. The effect on endothelial AJ was specific for PMN since adherent activated lymphocytes did not induce similar changes. High concentrations of protease inhibitors and oxygen metabolite scavengers were unable to prevent AJ disorganization mediated by PMN. PMN adhesion to EC was accompanied by increase in EC permeability in vitro. This effect was dependent on PMN adhesion, was not mediated by proteases and oxygen- reactive metabolites, and could be reproduced by EC treatment with EGTA. Finally, immunohistochemical analysis showed that VE-cadherin distribution was affected by PMN adhesion to the vessel wall in vivo too. This work suggests that PMN adhesion could trigger intracellular signals in EC that possibly regulate VE-cadherin /catenin complex disorganization. This effect could increase EC permeability and facilitate PMN transmigration during the acute inflammatory reaction.
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影响因子：
15.3
作者：
ALLAVENA, P;PAGANIN, C;MANTOVANI, A
通讯作者：
MANTOVANI, A
影响因子：
2.9
作者：
DEMONTELLANO, PRO;DAVID, SK;TEW, D
通讯作者：
TEW, D
钙粘蛋白和PECAM-1之间的空间和时间关系在人内皮细胞的细胞 - 细胞连接处。
影响因子：
7.8
作者：
Ayalon, O;Sabanai, H;Lampugnani, M G;Dejana, E;Geiger, B
通讯作者：
Geiger, B
影响因子：
7.8
作者：
LAMPUGNANI, MG;CORADA, M;CAVEDA, L;BREVIARIO, F;AYALON, O;GEIGER, B;DEJANA, E
通讯作者：
DEJANA, E
影响因子：
64.5
作者：
COWIN, P;KAPPRELL, HP;HYNES, RO
通讯作者：
HYNES, RO