DISRUPTION OF THE SUBENDOTHELIAL BASEMENT-MEMBRANE DURING NEUTROPHIL DIAPEDESIS IN AN INVITRO CONSTRUCT OF A BLOOD-VESSEL WALL
DISRUPTION OF THE SUBENDOTHELIAL BASEMENT-MEMBRANE DURING NEUTROPHIL DIAPEDESIS IN AN INVITRO CONSTRUCT OF A BLOOD-VESSEL WALL
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DOI：
10.1172/jci113992
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发表时间：
1989-04-01
影响因子：
15.9
通讯作者：
WEISS, SJ
中科院分区：
文献类型：
--
作者：
HUBER, AR;WEISS, SJ
为了研究外渗的中性粒细胞和内皮下基底膜之间的生理相互作用的过程中，微静脉血管壁的模型通过培养人脐静脉内皮细胞胶原基质。培养21天后，内皮细胞单层显示在体内样的细胞间边界和交界处，沉积单层，连续的基底膜，是不可穿透的胶体颗粒，并支持中性粒细胞外渗的生理方式。使用这个模型，我们证明了中性粒细胞在血浆环境中的迁移与基底膜的滞留特性的显着破坏，在没有明显的形态学变化。与中性粒细胞渗出相关的基底膜完整性丧失不依赖于中性粒细胞弹性蛋白酶或组织蛋白酶G，并且对针对中性粒细胞胶原酶、明胶酶和乙酰肝素酶的抑制剂具有抗性。尽管这种基质完整性的丧失无法预防，但基底膜缺陷仅在通过需要活性蛋白和RNA合成的机制由上覆内皮修复之前短暂表达。这些数据表明，中性粒细胞外渗和可逆性基底膜破坏是作为血管壁迁移的结果而发生的协调事件。
To examine the course of physiologic interactions between extravasating neutrophils and the subendothelial basement membrane, a model of the venular vessel wall was constructed by culturing human umbilical vein endothelial cells on a collagen matrix. After 21 d in culture, the endothelial cell monolayer displayed in vivo-like intercellular borders and junctions, deposited a single-layered, continuous basement membrane that was impenetrable to colloidal particles, and supported neutrophil extravasation in a physiologic manner. Using this model, we demonstrate that neutrophil transmigration in a plasma milieu was associated with a significant disruption of the retentive properties of the basement membrane in the absence of discernable morphologic changes. The loss of basement membrane integrity associated with neutrophil diapedesis was not dependent on neutrophil elastase or cathepsin G and was resistant to inhibitors directed against neutrophil collagenase, gelatinase, and heparanase. Despite the fact that this loss in matrix integrity could not be prevented, basement membrane defects were only transiently expressed before they were repaired by the overlying endothelium via a mechanism that required active protein and RNA synthesis. These data indicate that neutrophil extravasation and reversible basement membrane disruption are coordinated events that occur as a consequence of vessel wall transmigration.