Novel Characterization of Monocyte-Derived Cell Populations in the Meninges and Choroid Plexus and Their Rates of Replenishment in Bone Marrow Chimeric Mice

Novel Characterization of Monocyte-Derived Cell Populations in the Meninges and Choroid Plexus and Their Rates of Replenishment in Bone Marrow Chimeric Mice
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DOI:
10.1097/nen.0b013e3181edbc1a
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发表时间:
2010-09-01
影响因子:
3.2
通讯作者:
McMenamin, Paul G.
McMenamin, Paul G.
中科院分区:
医学4区
文献类型:
--
作者:
Chinnery, Holly R.;Ruitenberg, Marc J.;McMenamin, Paul G.

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小鼠硬脑膜、软脑膜和脉络丛含有常驻巨噬细胞和树突状细胞(DC)。这些细胞参与免疫监视、吞噬细胞碎片、从周围脑脊液中摄取抗原以及许多病理过程中的免疫调节。我们使用Cx(3)cr 1(gfp)基因敲入、CD 11 c-eYFP转基因和骨髓嵌合小鼠来表征脑膜和脉络丛中单核细胞衍生细胞的表型、密度和补充率,并评估趋化因子受体CX(3)CR 1对其数量和组织分布的作用。在脑膜和脉络丛完整标本中鉴定出Iba-1(+)主要组织相容性复合物(MHC)II类+CD 169(+)CD 68(+)巨噬细胞和CD 11 c(+)推定的DC。纯合子和杂合子Cx(3)cr 1(gfp)小鼠的比较没有显示CX(3)CR 1对单核细胞衍生细胞的密度、分布或表型的依赖性。在转换研究中,用Cx(3)cr 1/(gfp)阳性骨髓重建野生型致死性照射小鼠,并在移植后3天、1、2、4和8周进行分析。硬脑膜中CX(3)CR 1(gfp)阳性细胞迅速补充(4周时),脉络丛在8周时完全重建。这些数据为将来研究驻留巨噬细胞和树突状细胞在脑膜炎、自身免疫性炎症疾病等疾病中的作用以及在涉及放射和造血或干细胞移植的治疗中的作用提供了基础。
The mouse dura mater, pia mater, and choroid plexus contain resident macrophages and dendritic cells (DCs). These cells participate in immune surveillance, phagocytosis of cellular debris, uptake of antigens from the surrounding cerebrospinal fluid and immune regulation in many pathologic processes. We used Cx(3)cr1(gfp) knock-in, CD11c-eYFP transgenic and bone marrow chimeric mice to characterize the phenotype, density and replenishment rate of monocyte-derived cells in the meninges and choroid plexus and to assess the role of the chemokine receptor CX(3)CR1 on their number and tissue distribution. Iba-1(+) major histocompatibility complex (MHC) Class II+ CD169(+) CD68(+) macrophages and CD11c(+) putative DCs were identified in meningeal and choroid plexus whole mounts. Comparison of homozygous and heterozygous Cx(3)cr1(gfp) mice did not reveal CX(3)CR1-dependancy on density, distribution or phenotype of monocyte-derived cells. In turnover studies, wild type lethally irradiated mice were reconstituted with Cx(3)cr1/(gfp)-positive bone marrow and were analyzed at 3 days, 1, 2, 4 and 8 weeks after transplantation. There was a rapid replenishment of CX(3)CR1(gfp)-positive cells in the dura mater (at 4 weeks) and the choroid plexus was fully reconstituted by 8 weeks. These data provide the foundation for future studies on the role of resident macrophages and DCs in conditions such as meningitis, autoimmune inflammatory disease and in therapies involving irradiation and hematopoietic or stem cell transplantation.