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首页> 外文期刊>Transplant international : >The effect of allo-injury in an in vitro model of allograft microvasculature.
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The effect of allo-injury in an in vitro model of allograft microvasculature.

机译：同种异体损伤在同种异体移植微血管体外模型中的作用。

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Endothelial cells are critical to the integrity of allograft vasculature and can be damaged by alloreactive T cells or soluble mediators of alloreactivity. The biochemical effects of T cell-mediated damage to the endothelial cells have been studied, but not the structural and morphological effects of allo-injury on endothelial cells in the allograft. We utilized an assay that reproduces microvasculature in vitro to study the effect of alloreactivity on endothelial cells. In this assay, endothelial cells are induced into capillary-like networks that simulate microvascular capillaries. We studied the effect of allogeneic T cells and of soluble mediators from both mixed lymphocyte cultures (MLCs) and rejected heart allograft tissue on the in vitro capillaries. We found that both allogeneic T cells and soluble mediators inhibit the formation of the in vitro endothelial capillaries, suggesting that they cause a mild-to-moderate dysfunction of the endothelial cells. The inhibitory effect of the soluble mediators seems to be mediated, at least partly, by IFN-gamma, since this effect was prevented by antibody to IFN-gamma. Furthermore, pre-incubation of the in vitro capillaries with IFN-gamma appeared to magnify the effect of allogeneic T cells, as shown by a complete breakdown of well-formed in vitro capillary networks. Our experiments suggest that the in vitro capillary-tube model reflects structural injury to allograft vasculature by alloreactive T cells and their soluble mediators.
机译：内皮细胞对于同种异体移植血管的完整性至关重要，并且可能被同种异体反应性T细胞或同种异体反应性的可溶性介体破坏。已经研究了T细胞介导的对内皮细胞损伤的生化作用，但没有研究同种异体损伤对同种异体移植血管内皮细胞的结构和形态学影响。我们利用体外复制微脉管系统的试验来研究同种异体反应对内皮细胞的影响。在该测定中，内皮细胞被诱导成模拟微血管毛细血管的毛细管样网络。我们研究了异体T细胞和混合淋巴细胞培养（MLCs）和排斥心脏异体移植组织的可溶性介体对体外毛细血管的影响。我们发现同种异体T细胞和可溶性介体均抑制体外内皮毛细血管的形成，这表明它们引起了内皮细胞的轻度至中度功能障碍。可溶性介体的抑制作用似乎至少部分地由IFN-γ介导，因为该作用被针对IFN-γ的抗体阻止。此外，体外毛细血管与IFN-γ的预孵育似乎放大了同种异体T细胞的作用，这由结构良好的体外毛细血管网完全破裂所显示。我们的实验表明，体外毛细管模型反映了同种异体反应性T细胞及其可溶性介体对同种异体移植血管的结构损伤。

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