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Cellular Analysis of Cutaneous Granuloma induced by Antigen-binding Agarose Particle and MDP

抗原结合琼脂糖颗粒和 MDP 诱导的皮肤肉芽肿的细胞分析

基本信息

批准号：
13670903
负责人：
OKAMOTO Hiroyuki
金额：
$ 1.98万
依托单位：
Kansai Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670903/
关键词：
Granuloma Mice MDP Adjuvant DNP Monocyte Giant Cell T cell MDP 骨髄細胞インターフェロン IL-3

项目摘要

We examined immune cells and cytokine production in murine cutaneous granulomas induced by antigen-binding agarose particles and MDP. A few number of CD3+ cells are present in the center of granulomas and their surrounding areas. Almost same numbers of CD4+ and CD8+ cells are distributed. On the other hand, CD14+ monocytes are main cells of the granuloma, but tissure macrophages which are positive for MMGL were not present in the center of the granulomas. IFN-γ+ cells were more predominantly distributed than IL-4+ cells, suggesting that the induced cutaneous granuloma had a property of TH1 type reaction. To examine the propety of precursor cells of monocyte-macrophage lineage cells in the granulomas, the folowing cells were prepared from GFP-transgeneic mice, 1) peripheral monocytes, 2) macrophages induced by culturing monoctes, 3) MMGL+ dermal macrophages in normal skin, 4) peritoneal macrophages, 5) bone marrow cells, 6) dendritic cells induced from bone marrow cells with GM-CSF/IL-4. These cells were administered subcutaneously or intraveneously into granuloma-bearing mice. GFP+ cells were found in the granuloma only when freshly isolated bone marrow cells were injected. To investigate the response ofepithelioid cells in granuloma to cytokines, epithelioid cells were riched by eliminating CD3+ cells, B220+ cells and MMGL+ cells in the granulomas. Theses cells responded to IFN-γ and IL-3 but not to IL-13 or IL-10. These results suggest that infiltrating cells from bonw marrows consist of cutaneous granulomas induced by antigen-binding agarose particles and MDP, and that IFN-γ and EL-3 are a key factor for the formation of granulomas.

我们研究了抗原结合琼脂糖颗粒和MDP诱导的小鼠皮肤肉芽肿中免疫细胞和细胞因子的产生。在肉芽肿的中心及其周围区域存在少量的CD 3+细胞。几乎相同数量的CD 4+和CD 8+细胞分布。另一方面，肉芽肿的主要细胞为CD 14+单核细胞，但在肉芽肿中心不存在MMGL阳性的组织巨噬细胞。IFN-γ+细胞的分布较IL-4+细胞多，提示诱导的皮肤肉芽肿具有TH 1型反应的性质。为了检查肉芽肿中单核细胞-巨噬细胞谱系细胞的前体细胞的性质，从GFP转基因小鼠制备以下细胞：1）外周单核细胞，2）通过培养单核细胞诱导的巨噬细胞，3）正常皮肤中的MMGL+真皮巨噬细胞，4）腹腔巨噬细胞，5）骨髓细胞，6）用GM-CSF/IL-4从骨髓细胞诱导的树突状细胞。将这些细胞皮下或静脉内施用到携带肉芽肿的小鼠中。仅当注射新鲜分离的骨髓细胞时，在肉芽肿中才发现GFP+细胞。为了研究肉芽肿中上皮样细胞对细胞因子的反应，通过消除肉芽肿中的CD 3+细胞、B220+细胞和MMGL+细胞来富集上皮样细胞。这些细胞对IFN-γ和IL-3有反应，但对IL-13或IL-10无反应。提示骨髓浸润细胞由抗原结合琼脂糖颗粒和MDP诱导的皮肤肉芽肿组成，IFN-γ和EL-3是肉芽肿形成的关键因素。