Menges Mauritius, Baumeister Thomas, Rössner Susanne, Stoitzner Patrizia, Romani Nikolaus, Gessner André, Lutz Manfred B
Department of Dermatology, University Hospital Erlangen, Germany.
J Leukoc Biol. 2005 Apr;77(4):535-43. doi: 10.1189/jlb.0804473. Epub 2004 Dec 23.
Dendritic cells (DC) of myeloid origin can be generated from mouse bone marrow (BM) using granulocyte macrophage-colony stimulating factor (GM-CSF). Immature major histocompatibility complex (MHC) II(low) DC are known to bear a high endocytosis capacity, in contrast to DC precursors and mature DC. Now we found that a subset of MHC II(low) DC in BM-DC cultures is unable to exert mannose receptor-mediated endocytosis of fluorescein isothiocyanate (FITC)-dextran (DX) and resembles immature Langerhans cells (LC). The FITC-DX endocytosis activity of LC-like cells occurs at an earlier stage of development, where the surface MHC II expression is absent or very weak. This LC-like subset expresses higher levels of E-cadherin but lower amounts of the markers Gr-1, scavenger receptor 2F8, and CD11b, when compared with the highly endocytic DC subset. The latter myeloid DC resemble monocyte-derived DC (MoDC). The sorted LC-like population develops completely and exclusively into mature MHC IIhigh DC, and the MoDC-like cells remain immature MHC II(low) DC or develop into adherent MHC IIneg macrophages or mature into MHC IIhigh DC. The development of LC-like cells is promoted by interleukin-4. Thus, we show here that the simultaneous development of LC-like and MoDC-like DC subsets occurs in standard bulk cultures with GM-CSF, suggesting the existence of two different precursors for LC and MoDC in BM.
髓系来源的树突状细胞（DC）可通过粒细胞巨噬细胞集落刺激因子（GM-CSF）从小鼠骨髓（BM）中生成。与DC前体和成熟DC相比，未成熟的主要组织相容性复合体（MHC）II（低）DC具有较高的内吞能力。现在我们发现，BM-DC培养物中MHC II（低）DC的一个亚群无法发挥甘露糖受体介导的异硫氰酸荧光素（FITC）-葡聚糖（DX）内吞作用，且类似于未成熟的朗格汉斯细胞（LC）。LC样细胞的FITC-DX内吞活性出现在发育的早期阶段，此时表面MHC II表达缺失或非常弱。与高内吞性DC亚群相比，这个LC样亚群表达更高水平的E-钙黏蛋白，但Gr-1、清道夫受体2F8和CD11b等标志物的表达量较低。后者的髓系DC类似于单核细胞衍生的DC（MoDC）。分选得到的LC样群体完全且仅发育为成熟的MHC II高DC，而MoDC样细胞则保持未成熟的MHC II（低）DC状态，或发育为贴壁的MHC II阴性巨噬细胞，或成熟为MHC II高DC。白细胞介素-4可促进LC样细胞的发育。因此，我们在此表明，在含有GM-CSF的标准批量培养物中，LC样和MoDC样DC亚群会同时发育，这表明BM中存在两种不同的LC和MoDC前体。
