CpG oligodeoxynucleotide prolongs eosinophil survival through activation of contaminating B cells and plasmacytoid dendritic cells in vitro
CpG oligodeoxynucleotide prolongs eosinophil survival through activation of contaminating B cells and plasmacytoid dendritic cells in vitro
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DOI：
10.1159/000092710
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发表时间：
2006-01-01
影响因子：
2.8
通讯作者：
Saito, H
中科院分区：
文献类型：
--
作者：
Matsumoto, K;Terakawa, M;Saito, H
背景资料：在我们以前的研究中，含有未甲基化的CpG基序（CpG ODNs）的寡脱氧核苷酸显着延长嗜酸性粒细胞的生存，而不诱导嗜酸性粒细胞clerived神经毒素或白细胞介素8的主动释放。此外，这种存活促进活性是核因子-κ B依赖性的。然而，来自不同供体的一些嗜酸性粒细胞制剂对CpG ODN几乎没有反应。为了阐明为什么CpG ODN诱导的核因子-κ B在嗜酸性粒细胞中的活化不会引起嗜酸性粒细胞的神经毒素或白细胞介素8的释放，以及为什么在某些嗜酸性粒细胞制剂中没有发现CpG ODN的生存促进活性，我们确定了从人嗜酸性粒细胞制剂中广泛去除污染的B细胞和浆细胞样树突状细胞的效果。研究方法：用抗CD 16单用或联合抗CD 16、抗CID 19和抗血液树突状细胞抗原4（BDCA 4）免疫磁珠，通过梯度沉降和阴性选择从健康或轻度过敏供体外周血中纯化嗜酸性粒细胞。在与合成的CpG 2006（CpG-B）、CpG 2216（CpG-A）或它们的GpC对照ODN孵育24小时后，通过FACS用FITC缀合的膜联蛋白V和碘化丙啶测量嗜酸性粒细胞存活。结果：抗CD 19和抗BDCA 4免疫磁珠的加入可减少嗜酸性粒细胞中CD 19+和CD 123 + BDCA 2+细胞的数量。CpG 2006和CpG 2216，而不是它们的GpC对照ODN，显著延长了单独用抗CD 16免疫磁珠纯化的嗜酸性粒细胞的存活，但不延长用抗CD 16、抗CD 119和抗BDCA 4珠的组合纯化的嗜酸性粒细胞的存活。结论：这些结果强烈表明，污染的B细胞或浆细胞样树突状细胞在嗜酸性粒细胞制剂中的关键调节CpG ODN介导的嗜酸性粒细胞存活的延长，CpG ODN不直接激活嗜酸性粒细胞。版权所有（c）2006 S. Karger AG，巴塞尔。
Background: In our previous study, oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODNs) significantly prolonged eosinophil survival without inducing active release of eosinophil-clerived neurotoxin or interleukin 8. In addition, this survival-promoting activity was nuclear factor-kappa B dependent. However, some eosinophil preparations from different donors hardly responded to CpG ODNs at all. To clarify why CpG ODN-induced nuclear factor-kB activation in eosinophils does not cause eosinophil-clerived neurotoxin or interleukin 8 release and why the survival-promoting activity of CpG ODNs was not found in some eosinophil preparations, we determined the effect of extensive removal of contaminating B cells and plasmacytoid dendritic cells from human eosinophil preparations. Methods: Eosinophils were purified from the peripheral blood of healthy or slightly allergic donors by gradient sedimentation and negative selection with anti-CD16 alone or a combination of anti-CD16, anti-CID19 and anti-blood dendritic cell antigen 4 (BDCA4) immunomagnetic beads. Eosinophil survival was measured with FITC-conjugated annexin V and propidium iodide by FACS after incubation with synthetic CpG 2006(CpG-B), CpG 2216 (CpG-A) or their GpC control ODNs for 24 h. Results:The addition of anti-CD19 and anti-BDCA4 immunomagnetic beads reduced the number of contaminating CD19+ cells and CD123+ BDCA2+ cells in eosinophil preparations. CpG 2006 and CpG 2216, but not their GpC control ODNs, significantly prolonged survival of eosinophils purified with anti-CD16 immunomagnetic beads alone but not eosinophils purified with a combination of anti-CD16, anti-CD119 and anti-BDCA4 beads. Conclusions: These results strongly suggest that contaminating B cells or plasmacytoid dendritic cells in eosinophil preparations critically regulate CpG ODN-mediated prolongation of eosinophil survival and that CpG ODNs do not activate eosinophils directly. Copyright (c) 2006 S. Karger AG, Basel.