纤维蛋白原通过维持细胞表面连接蛋白-1在体外防止屏障功能障碍。
Fibrinogen Protects Against Barrier Dysfunction Through Maintaining Cell Surface Syndecan-1 In Vitro.
机构信息
Shock Trauma Center, University of Maryland School of Medicine, Baltimore, Maryland.
出版信息
Shock. 2019 Jun;51(6):740-744. doi: 10.1097/SHK.0000000000001207.
BACKGROUND
We have shown that fresh frozen plasma's (FFP) protection of pulmonary endothelial barrier integrity following hemorrhagic shock is due in part to restoration of endothelial syndecan-1. In the present study, we investigated the role of fibrinogen, a major component of FFP, as an endothelial protector and hypothesize that fibrinogen stabilizes cell surface syndecan-1 to restore endothelial barrier integrity.
METHODS
Pulmonary endothelial cells were incubated in FFP, fibrinogen, or lactated Ringers (LR) then immunostained with anti-syndecan-1 or fibrinogen and barrier integrity assessed. In some experiments, cells were exposed to fibrinogen depleted plasma.
RESULTS
Cell surface syndecan-1 was increased by FFP and fibrinogen compared with LR-treated cells while barrier integrity was augmented by FFP and fibrinogen compared with LR. The physiological concentration of 2.5 mg/mL fibrinogen was sufficient to increase cell surface syndecan-1. Colocalization and co-immunoprecipitation experiments demonstrated that fibrinogen associates with syndecan-1. Fibrinogen-deficient plasma was unable to augment sydnecan-1 immunostaining and lost its endothelial protective effect on barrier integrity.
CONCLUSION
These data suggest that in vitro, fibrinogen associated with cell surface syndecan-1 and enhanced endothelial barrier integrity.
背景
我们已经证明，新鲜冷冻血浆（FFP）对出血性休克后肺内皮屏障完整性的保护作用部分归因于内皮细胞硫酸乙酰肝素蛋白聚糖-1（syndecan-1）的恢复。在本研究中，我们研究了纤维蛋白原（FFP 的主要成分之一）作为内皮保护剂的作用，并假设纤维蛋白原稳定细胞表面 syndecan-1 以恢复内皮屏障完整性。
方法
将肺内皮细胞在 FFP、纤维蛋白原或乳酸林格氏液（LR）中孵育，然后用抗 syndecan-1 或纤维蛋白原进行免疫染色，评估内皮屏障的完整性。在一些实验中，细胞暴露于纤维蛋白原耗尽的血浆中。
结果
与 LR 处理的细胞相比，FFP 和纤维蛋白原增加了细胞表面 syndecan-1 的表达，而 FFP 和纤维蛋白原增加了内皮屏障的完整性。生理浓度的 2.5mg/mL 纤维蛋白原足以增加细胞表面 syndecan-1。共定位和共免疫沉淀实验表明纤维蛋白原与 syndecan-1 结合。缺乏纤维蛋白原的血浆无法增强 sydnecan-1 的免疫染色，并且丧失了对内皮屏障完整性的保护作用。
结论
这些数据表明，在体外，纤维蛋白原与细胞表面 syndecan-1 结合并增强了内皮屏障的完整性。
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