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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Hla-g Homodimer-induced Cytokine Secretion Through Hla-g Receptors On Human Decidual Macrophages And Natural Killer Cells
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Hla-g Homodimer-induced Cytokine Secretion Through Hla-g Receptors On Human Decidual Macrophages And Natural Killer Cells

机译:Hla-g Homodimer诱导的人蜕膜巨噬细胞和天然杀伤细胞上Hla-g受体的细胞因子分泌

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Human decidual CD14~+ macrophages and CD56~+ NK cells were isolated from material obtained after first-trimester pregnancy terminations. Each cell type expressed a specific surface receptor for histocompatibility leukocyte antigen (HLA)-G (an MHC class lb protein that is expressed on extravillous trophoblasts), LILRB1 on CD14~+ macrophages and KIR2DL4 on CD56~+ NK cells. Cross-linking with anti-LILRB1 or anti-KIR2DL4 resulted in up-regulation of a small subset of mRNAs including those for IL-6, IL-8, and TNFα detected using a microarray representing 114 cytokines. Incubation with transfectants expressing the HLA-G homodimer (but not with transfectants expressing the HLA-G monomer) resulted in secretion of the same cytokine proteins from both leukocyte sets. Moreover, cytokine secretion from both leukocyte sets was blocked by both the appropriate anti-receptor mAb and by anti-HLA-G. The amount of these cytokines secreted by decidual macrophages was substantially greater than that secreted by decidual NK cells. VEGF was constitutively secreted by both cell types. LILRB1, which contains an immunoreceptor tyrosine-based switch motif, functions here as an activating receptor, although it has been known as an inhibitory receptor. KIR2DL4 also functions as an activating receptor, although it also has the potential to function as an inhibitory receptor. Secretion of proinflammatory and proangiogenic proteins supports a role for these leukocytes in important processes that are essential for successful pregnancy, but they may represent only a portion of the proteins that are secreted.
机译:从早孕终止后获得的物质中分离出人蜕膜CD14〜+巨噬细胞和CD56〜+ NK细胞。每种细胞类型均表达组织相容性白细胞抗原(HLA)-G(在绒毛外滋养层细胞中表达的MHC Ib类蛋白),CD14〜+巨噬细胞上的LILRB1和CD56〜+ NK细胞上的KIR2DL4的特异性表面受体。与抗LILRB1或抗KIR2DL4交联导致一小部分mRNA上调,包括使用代表114种细胞因子的微阵列检测到的IL-6,IL-8和TNFα的mRNA。与表达HLA-G同型二聚体的转染子(但不与表达HLA-G单体的转染子)一起温育导致从两个白细胞组分泌相同的细胞因子蛋白。此外,适当的抗受体mAb和抗HLA-G均可阻断两种白细胞中细胞因子的分泌。蜕膜巨噬细胞分泌的这些细胞因子的数量显着大于蜕膜NK细胞分泌的细胞因子的数量。两种细胞均组成型分泌VEGF。 LILRB1包含一个基于免疫受体酪氨酸的开关基序,尽管它被称为抑制受体,但在这里起着激活受体的作用。 KIR2DL4还具有激活受体的功能,尽管它也具有抑制受体的功能。促炎和促血管生成蛋白的分泌支持这些白细胞在成功怀孕所必需的重要过程中发挥作用,但它们可能仅代表所分泌蛋白的一部分。

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