Distinct alterations of CD68(+)CD163(+) M2-like macrophages and myeloid-derived suppressor cells in newly diagnosed primary immune thrombocytopenia with or without CR after high-dose dexamethasone treatment.

Distinct alterations of CD68(+)CD163(+) M2-like macrophages and myeloid-derived suppressor cells in newly diagnosed primary immune thrombocytopenia with or without CR after high-dose dexamethasone treatment.
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高剂量地塞米松治疗后新诊断的原发性免疫性血小板减少症伴或不伴 CR 中 CD68 CD163 M2 样巨噬细胞和骨髓源性抑制细胞的明显改变

DOI:
10.1186/s12967-018-1424-8
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发表时间:
2018-03-02
影响因子:
7.4
通讯作者:
Cheng Y
Cheng Y
中科院分区:
医学2区
文献类型:
--
作者:
Shao X;Wu B;Cheng L;Li F;Zhan Y;Liu C;Ji L;Min Z;Ke Y;Sun L;Chen H;Cheng Y

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虽然受损的髓源性抑制细胞(MDSC)最近已在免疫性血小板减少症(ITP)中进行了研究,但另一种髓源性细胞群(表示为M2巨噬细胞)尚未在ITP患者中进行适当研究。在本研究中,我们旨在确定循环M2样巨噬细胞的特征,检查其与MDSC的关系,并探讨其在ITP中的预后价值。分离来自健康对照和原发性ITP患者的外周血单核细胞以测试循环M2样巨噬细胞和MDSC。通过流式细胞术测定循环M2样巨噬细胞群(定义为CD 68 + CD 163+)和循环MDSC群(定义为CD 11b + CD 33 +HLA-DR−)。采用多重ELISA法检测血浆炎症细胞因子。初诊ITP患者MDSC的百分比增加,尤其是完全缓解(CR)组(p < 0.0001)。M2样巨噬细胞和MDSC的百分比之间证实了正线性相关性。在CR组中也确定了相同的相关性。治疗后,CR组M2样巨噬细胞和MDSC的百分比均显著增加,PR + NR组MDSC的百分比显著减少,而M2样巨噬细胞的百分比仅中度减少。MIP-1α/CCL 3与M2样巨噬细胞呈负相关,MCP-1与M2样巨噬细胞呈正相关,Eotaxin-1/CCL 11与MDSCs呈负相关,IL-1 β与M2样巨噬细胞和MDSCs均呈负相关。目前的研究结果表明,循环M2样巨噬细胞和MDSC在ITP中的关键作用。它们之间的正相关性可能与炎症因子介导的双向相互作用有关,或者部分是由于它们在分化过程中相似的背景模式。MIP-1α/CCL 3、MCP-1、eotaxin-1/CCL 11和IL-1β可能在ITP患者M2巨噬细胞和MDSCs的增殖中起重要作用,值得进一步研究。本文的在线版本(10.1186/s12967-018-1424-8)包含补充材料,可供授权用户使用。
Although impaired myeloid-derived suppressor cells (MDSCs) recently have been studied in immune thrombocytopenia (ITP), another myeloid-derived cell population signified as M2 macrophages has not been investigated properly in ITP patients. In the present study, we intended to determine the features of circulating M2-like macrophages, to examine its relationship with MDSCs, and to explore their prognostic values in ITP. Peripheral blood mononuclear cells from healthy controls and primary ITP patients were isolated to test the circulating M2-like macrophages and MDSCs. The circulating M2-like macrophage population defined as CD68+CD163+ and circulating MDSC population as CD11b+CD33+HLA-DR− were determined by flow cytometry. Plasma inflammatory cytokines were measured by multiplex ELISA. The percentages of MDSCs were found to be expanded in newly diagnosed patients of ITP, especially among those of the complete response (CR) group (p < 0.0001). Positive linear correlation was verified between percentages of M2-like macrophages and MDSCs. The same correlation was also determined in the CR group. After treatment, the percentages of M2-like macrophages and MDSCs were both increased significantly in CR group, while those patients among the PR + NR group manifested a significant numeric decrease of MDSCs but only a moderate decrease in M2-like macrophages. MIP-1α/CCL3 was negatively correlated with M2-like macrophages while MCP-1 possessed a positive correlation with M2-like macrophages, eotaxin-1/CCL11 was negatively correlated with MDSCs and interleukin-1β (IL-1β) was found to be negatively correlated with both M2-like macrophages and MDSCs. The present findings indicated critical roles of both circulating M2-like macrophages and MDSCs in ITP. The positive correlation between them might be related to inflammatory factors-mediated bidirectional interactions or partially due to their similar background patterns during differentiation. MIP-1α/CCL3, MCP-1, eotaxin-1/CCL11 and IL-1β might play a critical role in the expansion of both M2 macrophages and MDSCs population in ITP patients, which deserves further investigation. The online version of this article (10.1186/s12967-018-1424-8) contains supplementary material, which is available to authorized users.
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