Human platelets express heat shock protein receptors and regulate dendritic cell maturation
Human platelets express heat shock protein receptors and regulate dendritic cell maturation
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DOI：
10.1182/blood.v99.10.3676
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发表时间：
2002-05-15
期刊：
影响因子：
20.3
通讯作者：
Schild, H
中科院分区：
文献类型：
--
作者：
Hilf, N;Singh-Jasuja, H;Schild, H
使用内质网-REWNT热休克蛋白Gp 96的免疫诱导特异性免疫应答。特异性基于来源于内源性蛋白质的Gp 96相关肽的主要组织相容性复合体1类限制性交叉呈递。免疫应答的启动依赖于Gp 96诱导巨噬细胞和树突状细胞（DC）产生促炎细胞因子的能力以及它们以一种可能独立于相关肽的方式成熟的能力。这两个事件都是由抗原呈递细胞上的Gp 96受体介导的。已知Gp 96在例如由病毒感染诱导的坏死时从细胞中释放。虽然该事件支持有效诱导免疫应答，但它也可能干扰易受慢性炎症影响的过程，例如组织损伤后的伤口愈合。因此，Gp 96介导的免疫系统刺激需要严格的调节。在这里，我们表明，人类血小板特异性地与Gp 96相互作用，Gp 96与血小板的结合增强了10倍以上的凝血酶激活。Gp 96既不干扰凝血酶诱导的血小板活化，也不干扰血小板聚集。然而，在Gp 96介导的DC活化过程中血小板的存在减少了促炎细胞因子的分泌和DC的活化。这种作用不依赖于可溶性血小板因子和DC与血小板之间的细胞-细胞接触。因此，我们提供了证据的调节机制，中和Gp 96分子全身，特别是在血液中。这种效应在必须预防慢性炎症和针对自身抗原的免疫反应的伤口中可能具有重要意义。(C)2002年，美国血液学会。
Immunizations using the endoplasmic reticulum-res Went heat shock protein Gp96 induce specific Immune responses. Specificity Is based on the major histocompatibility complex class 1-restricted cross-presentation of Gp96-associated peptides derived from endogenous proteins. Initiation of the immune response depends on the ability of Gp96 to Induce the production of proinflammatory cytokines by macrophages and dendritic cells (DCs) and of their maturation in a fashion presumably independent of associated peptide. Both events are mediated by Gp96 receptors on antigen-presenting cells. It is known that Gp96 Is released from cells at necrosis induced, for example, by virus Infection. Although this event supports the efficient induction of immune responses, it might also interfere with processes that are susceptible to chronic Inflammation, such as wound healing after tissue damage. Therefore, Gp96-mediated stimulation of the immune system requires tight regulation. Here we show that human thrombocytes specifically interact with Gp96 and that binding of Gp96 to platelets is enhanced more than 10-fold on activation by thrombin. Gp96 interferes with neither thrombin-induced platelet activation nor platelet aggregation. However, the presence of platelets during Gp96-mediated DC activation reduces the secretion of proinflammatory cytokines and the activation of DCs. This effect is independent of soluble platelet factors and cell-to-cell contact between DCs and thrombocytes. Thus, we provide evidence for a regulatory mechanism that neutralizes Gp96 molecules systemically, especially In the blood. This effect might be of significance In wounds in which chronic inflammation and immune responses against autoantigens have to be prevented. (C) 2002 by The American Society of Hematology.