Dendritic cells lower the permeability of endothelial monolayers.
Dendritic cells lower the permeability of endothelial monolayers.
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DOI：
10.1007/s12195-012-0220-4
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发表时间：
2012-06
影响因子：
2.8
通讯作者：
Weinberg PD
中科院分区：
文献类型：
--
作者：
Warboys CM;Overby DR;Weinberg PD
体外培养的内皮单层通透性高于活体内皮通透性。与星形胶质细胞共培养可在体外诱导主动脉内皮致密的血脑屏障表型。我们假设存在于非脑动脉内膜的树突状细胞与星形胶质细胞具有共同的特征，也可能降低培养的主动脉内皮的通透性。通过与树突状细胞（但不是来源于外周血单核细胞）和树突状细胞条件培养基的非接触共培养，猪主动脉内皮单层的通透性降低，表明存在可溶性介质。通透性降低与星形胶质细胞共培养相似；然而，树突状细胞没有上调p-糖蛋白，也没有与慢性剪切应力对通透性的影响协同作用，这与星形胶质细胞的观察结果相反。鞘氨醇-1-磷酸介导血小板的屏障收紧作用，可降低内皮细胞的通透性，但鞘氨醇-1-磷酸受体抑制剂不能阻断树突状细胞的作用。内皮细胞有丝分裂率和细胞凋亡率也不受共培养的影响。因此，树突状细胞降低通透性的机制不同于星形胶质细胞和血小板的屏障收紧作用，尽管可能涉及慢性剪切应力降低通透性的因素。我们推测树突状细胞影响内皮细胞的通透性。
The permeability of cultured endothelial monolayers is higher than the permeability of endothelium in vivo. Co-culture with astrocytes can induce a tight, blood-brain-barrier phenotype in aortic endothelium in vitro. We hypothesised that dendritic cells, which reside in the intima of non-cerebral arteries and have features in common with astrocytes, may also reduce the permeability of cultured aortic endothelium. The permeability of porcine aortic endothelial monolayers was reduced by non-contact co-culture with dendritic cells (but not with the peripheral blood monocytes from which they were derived) and by dendritic cell conditioned medium, indicating a soluble mediator. The reduction in permeability was similar to that obtained by co-culture with astrocytes; however, dendritic cells did not up-regulate P-glycoprotein and there was no synergy with the effect of chronic shear stress on permeability, contrary to observations with astrocytes. Endothelial permeability was reduced by sphingosine-1-phosphate, which mediates the barrier-tightening effect of platelets, but inhibitors of sphingosine-1-phosphate receptors did not block the effect of dendritic cells. Rates of endothelial mitosis and apoptosis were also unaffected by co-culture. Hence dendritic cells reduce permeability by different mechanisms from those mediating barrier-tightening effects of astrocytes and platelets, although factors mediating the permeability-lowering effects of chronic shear stress may be involved. We speculate that dendritic cells influence endothelial permeability in vivo.
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