Differential capability for phagocytosis of apoptotic and necrotic leukemia cells by human peripheral blood dendritic cell subsets
Differential capability for phagocytosis of apoptotic and necrotic leukemia cells by human peripheral blood dendritic cell subsets
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DOI：
10.1189/jlb.1204711
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发表时间：
2005-05-01
影响因子：
5.5
通讯作者：
Brinchmann, JE
中科院分区：
文献类型：
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作者：
Dalgaard, J;Beckstrom, KJ;Brinchmann, JE
CD 11 c（+）树突状细胞（DC）和浆细胞样DC（PDC）是人外周血中两种主要的DC亚群。研究不同来源的DC亚群对肿瘤细胞的吞噬作用，对于DC的免疫治疗具有重要意义。以天然单核细胞来源的DC（iMoDC）为参照，比较CD 11 c（+）DC和PDC吞噬凋亡和坏死的K562白血病细胞的能力。新鲜分离的CD 11 c（+）DC吞噬凋亡和坏死的K562细胞，而PDC没有显示出任何摄取死细胞的证据。阻断研究表明，CD 36在凋亡和坏死物质的摄取中起重要作用。CD 91和CD 11 e也参与其中。此外，我们发现β 5整合素在CD 11 c（+）DC上表达，但不与α V经典相关。在与粒细胞巨噬细胞集落刺激因子（GMCSF）和白细胞介素（IL）-4单独或与转化生长因子-β 1联合孵育后，CD 11 c（+）DC对凋亡K562细胞的摄取增加至与iMoDC观察到的水平相当。GM-CSF/IL-4处理的CD 11 c（+）DC对死亡细胞物质的吞噬作用主要限于表达低水平人白细胞自身抗原-DR和CD 83的亚群。因此，CD 11 c（+）DC和MoDC吞噬抗原物质和表达成熟相关细胞表面分子之间的关系是相似的。结论：外周血中的CD 11 c（+）DC是前体细胞，在细胞因子的作用下分化为具有DC表型和功能的细胞。
CD11c(+) dendritic cells (DC) and plasmacytoid DC (PDC) are the two major DC subsets in human peripheral blood. For the purpose of immunotherapy with DC, it is important to investigate the phagocytosis of killed tumor cells by different ferent DC subsets. Using inunature monocyte-derived DC (iMoDC) as reference, we have compared the ability of CD11c(+) DC and PDC to phagocytose apoptotic and necrotic K562 leukemia cells. Freshly isolated CD11c(+) DC phagocytosed apoptotic and necrotic K562 cells, whereas PDC did not show any evidence of uptake of dead cells. Blocking studies showed that CD36 is importantly involved in uptake of apoptotic and necrotic material. CD91 and CD11e were also involved. In addition, we found that beta 5 integrin was expressed on CD11c(+) DC but not in its classical association with alpha V. Uptake of apoptotic K562 cells by CD11c(+) DC was increased following incubation with granulocyte macrophage-colony stimulating factor (GMCSF) and interleukin (IL)-4, alone or in combination with transforming growth factor-beta 1, to levels comparable with those observed for iMoDC. Phagocytosis of dead cellular material by the GM-CSF/IL-4-treated CD11c(+) DC was largely restricted to a subset expressing low levels of human leukocyte autigen-DR and CD83. Thus, the relation,ship between phagocytosis of antigenic material and expression of maturation-related cell-surface molecules is similar for CD11c(+) DC and MoDC. We conclude that CD11c(+) DC in peripheral blood are precursor cells, which under the influence of cytokines differentiate to cells with DC phenotype and function.