Sunderkötter Cord, Nikolic Tatjana, Dillon Marilyn J, Van Rooijen Nico, Stehling Martin, Drevets Douglas A, Leenen Pieter J M
Institute of Experimental Dermatology and Department of Dermatology, University of Münster, Münster, Germany.
J Immunol. 2004 Apr 1;172(7):4410-7. doi: 10.4049/jimmunol.172.7.4410.
Blood monocytes are well-characterized precursors for macrophages and dendritic cells. Subsets of human monocytes with differential representation in various disease states are well known. In contrast, mouse monocyte subsets have been characterized minimally. In this study we identify three subpopulations of mouse monocytes that can be distinguished by differential expression of Ly-6C, CD43, CD11c, MBR, and CD62L. The subsets share the characteristics of extensive phagocytosis, similar expression of M-CSF receptor (CD115), and development into macrophages upon M-CSF stimulation. By eliminating blood monocytes with dichloromethylene-bisphosphonate-loaded liposomes and monitoring their repopulation, we showed a developmental relationship between the subsets. Monocytes were maximally depleted 18 h after liposome application and subsequently reappeared in the circulation. These cells were exclusively of the Ly-6C(high) subset, resembling bone marrow monocytes. Serial flow cytometric analyses of newly released Ly-6C(high) monocytes showed that Ly-6C expression on these cells was down-regulated while in circulation. Under inflammatory conditions elicited either by acute infection with Listeria monocytogenes or chronic infection with Leishmania major, there was a significant increase in immature Ly-6C(high) monocytes, resembling the inflammatory left shift of granulocytes. In addition, acute peritoneal inflammation recruited preferentially Ly-6C(med-high) monocytes. Taken together, these data identify distinct subpopulations of mouse blood monocytes that differ in maturation stage and capacity to become recruited to inflammatory sites.
血液单核细胞是巨噬细胞和树突状细胞特征明确的前体细胞。人类单核细胞亚群在各种疾病状态下具有不同的表现，这是众所周知的。相比之下，小鼠单核细胞亚群的特征描述极少。在本研究中，我们鉴定出小鼠单核细胞的三个亚群，它们可通过Ly-6C、CD43、CD11c、MBR和CD62L的差异表达来区分。这些亚群具有广泛吞噬作用的特征、M-CSF受体（CD115）的相似表达，并且在M-CSF刺激下发育为巨噬细胞。通过用负载二氯亚甲基双膦酸盐的脂质体清除血液单核细胞并监测其再填充情况，我们展示了这些亚群之间的发育关系。脂质体应用后18小时，单核细胞被最大程度地清除，随后重新出现在循环中。这些细胞仅为Ly-6C(高)亚群，类似于骨髓单核细胞。对新释放的Ly-6C(高)单核细胞进行的连续流式细胞术分析表明，这些细胞在循环中时Ly-6C表达下调。在由单核细胞增生李斯特菌急性感染或大利什曼原虫慢性感染引起的炎症条件下，未成熟的Ly-6C(高)单核细胞显著增加，类似于粒细胞的炎症左移。此外，急性腹膜炎症优先募集Ly-6C(中-高)单核细胞。综上所述，这些数据鉴定出了小鼠血液单核细胞的不同亚群，它们在成熟阶段和被募集到炎症部位的能力方面存在差异。
