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首页> 外文期刊>Transplant immunology >Expression patterns of integrin receptors and extracellular matrix proteins in chronic rejection of human liver allografts.
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Expression patterns of integrin receptors and extracellular matrix proteins in chronic rejection of human liver allografts.

机译：整合素受体和细胞外基质蛋白在人类肝脏同种异体移植慢性排斥反应中的表达模式。

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The beta1-integrin family of adhesion molecules is supposed to mediate cell-to-matrix interactions involved in a variety of immune reactions, especially in those associated with tissue remodelling. In an attempt to determine the role of beta1-integrins in the initiation and maintenance of fibrotic deposition observed in chronic rejection after liver transplantation, we immunohistochemically analysed the expression of different extracellular matrix components and the very late antigen (VLA) family of beta1-integrins in 11 samples of chronically rejected human liver allografts and compared results to findings in acutely rejected transplants and nontransplanted chronic inflammatory livers. In contrast to normal liver specimens, chronically rejected human liver allografts displayed a general overexpression of matrix components along sinusoids throughout the tissue and an additional characteristic accumulation in pericentral areas. Accordingly, VLA-1, -5 and -6 demonstrated a linear upregulation or de novo expression on sinusoidal lining cells, VLA-1 and VLA-4 additionally displayed concentration within pericentral fibrotic deposits. VLA-2 and -3 were only sporadically found. In accordance with findings in chronic rejection, chronic inflammatory livers showed overexpression of VLA-1, -5 and -6 within sinusoids and accumulation of VLA-1 and -4 in fibrotic septa. In contrast, acutely rejected allografts displayed slight overexpression of ECM components without characteristic accumulates, hence beta1-integrins were seen to be equally distributed throughout the parenchyma. Altogether, our analysis showed an upregulation of integrin receptors which corresponded to the extent of ECM deposition and thus suggested an important role for these molecules in the iniation of fibrosis observed in these specimens. Individual integrins showed different expression patterns within sinusoids and fibrotic areas, indicating distinct roles in differential stages of matrix accumulation, but induction patterns were generally similar in chronic inflammatory and chronically rejected livers, suggesting independence of the underlying disease.
机译：粘附分子的β1整合素家族被认为可以介导细胞与基质之间的相互作用，这些相互作用涉及多种免疫反应，尤其是与组织重塑相关的免疫反应。为了确定β1-整合素在肝移植后慢性排斥反应中观察到的纤维化沉积的启动和维持中的作用，我们免疫组化分析了不同细胞外基质成分和β1-整合素的晚期抗原（VLA）家族的表达。在11个慢性排斥人肝同种异体移植样品中，将结果与急性排斥性移植和未移植的慢性炎症性肝中的发现进行了比较。与正常肝脏标本相反，长期排斥的人类肝脏同种异体移植物沿整个组织的正弦曲线显示出基质成分的普遍过表达，并且在中央周围区域有额外的特征性积累。因此，VLA-1，-5和-6在正弦内衬细胞上表现出线性上调或从头表达，VLA-1和VLA-4在中心周围纤维化沉积物中还显示出浓度。仅偶尔发现VLA-2和-3。根据慢性排斥反应的发现，慢性炎症性肝在窦内显示出VLA-1，-5和-6的过度表达，并在纤维化隔中积累了VLA-1和-4。相反，急性排斥的同种异体移植物显示出ECM成分略有过度表达，而没有特征性的积累，因此，β1-整联蛋白在整个薄壁组织中均等分布。总而言之，我们的分析表明整合素受体的上调与ECM沉积的程度相对应，因此暗示了这些分子在这些样本中观察到的纤维化信号中起着重要的作用。单个整联蛋白在正弦波和纤维化区域内显示不同的表达模式，表明在基质积累的不同阶段具有不同的作用，但是在慢性炎症和慢性排斥的肝脏中诱导模式通常相似，表明潜在疾病的独立性。

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