Heparan Sulfate Proteoglycan Metabolism and the Fate of Grafted Tissues.

Heparan Sulfate Proteoglycan Metabolism and the Fate of Grafted Tissues.
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硫酸乙酰肝素蛋白多糖代谢和移植组织的命运。

DOI:
10.1007/978-3-319-18603-0_8
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发表时间:
2015
影响因子:
--
通讯作者:
Cascalho,Marilia
Cascalho,Marilia
中科院分区:
医学4区
文献类型:
--
作者:
Platt,JeffreyL;Wrenshall,LucileE;Johnson,GeoffreyB;Cascalho,Marilia

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基因不同个体之间的组织和器官移植总是或几乎总是被拒绝。移植排斥的普遍性和速度使这种免疫反应与所有其他免疫反应区分开来。虽然这种区别是不完全理解,一些努力,以阐明移植排斥反应揭示了更广泛的见解,包括移植组织中的补体激活,硫酸乙酰肝素蛋白多糖的代谢和免疫和炎症反应的性质,随之而来的关系。细胞表面,特别是内皮细胞表面上的补体活化导致硫酸乙酰肝素(一种酸性糖)从细胞表面和邻近的细胞外基质脱落。以这种方式溶解的硫酸乙酰肝素可以通过toll样受体-4激活白细胞,引发炎症反应并激活树突状细胞,树突状细胞迁移到区域淋巴器官,在那里它们激发并在一定程度上控制细胞免疫反应。这样,局部缺血、组织损伤和感染对免疫力产生全身性影响。这一系列事件是否或在何种情况下解释了对移植物的免疫反应的独特特征尚不清楚,但这些事件提供了在伴随感染的次优条件下免疫的开始以及感染和组织损伤引起全身炎症的机制的见解。
Tissue and organ transplants between genetically distinct individuals are always or nearly always rejected. The universality and speed of transplant rejection distinguishes this immune response from all others. Although this distinction is incompletely understood, some efforts to shed light on transplant rejection have revealed broader insights, including a relationship between activation of complement in grafted tissues, the metabolism of heparan sulfate proteoglycan and the nature of immune and inflammatory responses that ensue. Complement activation on cell surfaces, especially on endothelial cell surfaces, causes the shedding heparan sulfate, an acidic saccharide, from the cell surface and neighboring extracellular matrix. Solubilized in this way, heparan sulfate can activate leukocytes via toll like receptor-4, triggering inflammatory responses and activating dendritic cells, which migrate to regional lymphoid organs where they spark and to some extent govern cellular immune responses. In this way local ischemia, tissue injury and infection, exert systemic impact on immunity. Whether or in what circumstances this series of events explains the distinct characteristics of the immune response to transplants is still unclear but the events offer insight into the inception of immunity under the sub-optimal conditions accompanying infection and mechanisms by which infection and tissue injury engender systemic inflammation.
可溶性抗原诱导 T 淋巴细胞分泌糖苷内切酶,降解内皮下细胞外基质的硫酸乙酰肝素部分
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