Mouse peritoneal cells as a reservoir of late dendritic cell progenitors
Mouse peritoneal cells as a reservoir of late dendritic cell progenitors
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DOI：
10.1046/j.1365-2141.1999.01138.x
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发表时间：
1999-01
影响因子：
6.5
通讯作者：
R. Rezzani;L. Rodella;G. Zauli;L. Caimi;M. Vitale
中科院分区：
文献类型：
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作者：
R. Rezzani;L. Rodella;G. Zauli;L. Caimi;M. Vitale
尽管树突状细胞（DCs）在免疫生理学和相关疾病中发挥着关键作用，但其分化途径尚未完全阐明。在这项研究中，我们证明了从小鼠腹腔灌洗获得的细胞可以通过添加最佳浓度的小鼠重组GM-CSF（50 U/ml）6 d来诱导体外沿着树突状谱系分化。在形态学分析中，GM-CSF处理的腹膜细胞似乎松散地粘附在塑料上，并显示出典型的DC细胞质突起和面纱。在GM-CSF处理后，还在腹膜细胞中观察到DC表型标志物MIDC 8、DEC 205、CD 11 c和relB的重新表达，以及表面MHC-II的上调和非特异性酯酶（NSE）的完全下调。在功能上，GM-CSF处理的腹膜细胞在混合淋巴细胞反应中具有高度刺激性，表现出乳胶颗粒吞噬作用降低和胞饮活性增强。此外，肿瘤坏死因子（TNF）-α（5-10 ng/ml）能够与GM-CSF协同诱导DC分化。另一方面，当在腹膜收获前通过在体内用巯基乙酸盐处理动物来诱导腹膜细胞分化为巨噬细胞时，它们完全丧失了在体外获得对GM-CSF（单独使用或与TNF-α联合使用）应答的树突状表型的能力。这些结果通过有限稀释实验证实，该实验证明腹膜细胞在单细胞水平分化为DC。总之，这些数据表明，小鼠的静息腹膜细胞代表一个不成熟的群体，能够进一步分化沿着树突或巨噬细胞通路，这取决于它们接受的刺激类型。
Despite the key role played by dendritic cells (DCs) in the physiology of immunity and related diseases, their differentiation pathway has not yet been fully elucidated. In this study we demonstrated that cells obtained from mouse peritoneal cavity lavage can be induced to differentiate in vitro along the dendritic lineage by the addition of optimal concentrations of murine recombinant GM‐CSF (50 U/ml) for 6 d. At morphological analysis, GM‐CSF‐treated peritoneal cells appeared loosely adherent to plastic and showed cytoplasmic protrusions and veils typical of DCs. A de novo expression of the DC phenotypic markers MIDC8, DEC205, CD11c and relB with up‐regulation of surface MHC‐II and complete down‐regulation of non‐specific esterase (NSE) was also observed in peritoneal cells upon GM‐CSF treatment. Functionally, GM‐CSF‐treated peritoneal cells were highly stimulatory in a mixed lymphocyte reaction, showed a reduced phagocytosis of latex particles and enhanced pinocytic activity. Moreover, tumour necrosis factor (TNF)‐α (5–10 ng/ml) was able to synergize with GM‐CSF in the induction of DC differentiation. On the other hand, when peritoneal cells were induced to differentiate into macrophages by treating in vivo the animals with thioglycollate before peritoneal harvesting, they completely lost the ability to acquire in vitro the dendritic phenotype in response to GM‐CSF, either used alone or in combination with TNF‐α. These results were confirmed by limiting dilution experiments which demonstrated the differentiation of peritoneal cells into DCs at the single cell level. Taken together, these data suggest that resting peritoneal cells in the mouse represent an immature population, capable of further differentiation along either the dendritic or the macrophagic pathway, depending on the type of stimuli they receive.