中文摘要:
巨噬细胞具有多种功能,包括免疫调节、形态发生、组织稳态和愈合反应。目前的观点认为,乳腺巨噬细胞在青春期前期出生后出现,来源于骨髓衍生的单核细胞。在此,我们通过高维表型分析、细胞命运追踪实验、缺失特定巨噬细胞亚型的基因缺陷小鼠以及基于抗体的消耗策略,阐明了组织驻留乳腺巨噬细胞的起源。我们发现,组织驻留巨噬细胞在出生前便存在于乳腺中,而且卵黄囊来源和胎肝来源的巨噬细胞在成年乳腺中数量仍多于成人来源的巨噬细胞。此外,胎儿来源的乳腺巨噬细胞具有特征性表型,显示出偏向导管周围和血管周围的定位,并在清除功能上非?;钤?。这些发现将胎儿来源的巨噬细胞确定为成年乳腺基质中主要的白细胞类型,并揭示了乳腺巨噬细胞生物学此前未知的复杂性。
英文摘要:
Macrophages serve multiple functions including immune regulation, morphogenesis, tissue homeostasis and healing reactions. The current paradigm holds that mammary gland macrophages first arise postnatally during the prepubertal period from the bone marrow-derived monocytes. Here we delineate the origins of tissue-resident mammary gland macrophages using high-dimension phenotypic analyses, cell-fate mapping experiments, gene-deficient mice lacking selective macrophage subtypes, and antibody-based depletion strategies. We show that tissue-resident macrophages are found in mammary glands already before birth, and that the yolk sac-derived and fetal liver-derived macrophages outnumber the adult-derived macrophages in the mammary gland also in the adulthood. In addition, fetal-derived mammary gland macrophages have a characteristic phenotype, display preferential periductal and perivascular localization, and are highly active in scavenging. These findings identify fetal-derived macrophages as the predominant leukocyte type in the adult mammary gland stroma, and reveal previously unknown complexity of macrophage biology in the breast.
论文信息:
论文题目:Fetal-derived macrophages dominate in adult mammary glands
期刊名称:Nature Communications
时间期卷:10, Article number: 281(2019)
在线时间:2019年1月17日
DOI: doi.org/10.1038/s41467-018-08065-1
产品信息:
货号:CP-005-005
规格:5ml+5ml
品牌:Liposoma
产地:荷兰
名称:Clodronate Liposomes&Control liposomes
办事处:Target Technology(靶点科技)
Clodronate Liposomes氯膦酸盐脂质体联合抗体清除外周和乳腺定居巨噬细胞 ,荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Nature Communications:胎源性巨噬细胞在成年乳腺中占主导地位。

Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除乳腺巨噬细胞的材料和方法:
To deplete YS-derived macrophages pregnant female mice were treated with a single injection of CSF-1R blocking antibody (clone AFS98, Bio X Cell) or rat IgG2a control antibody (clone 2A3, Bio X Cell). Three mg of the antibodies in sterile PBS were administered i.p. to pregnant females at E6.5, as described12,32. Mice were sacrificed at E17.5 or at postnatal age of 2 wk or 5 wk for flow cytometric analyses.
To deplete tissue-resident macrophages after birth, 2 wk old C57Bl/6N mice were cyclically treated with anti-CSF1 antibody and clodronate (Fig. 2b). To that end, three doses of CSF1 neutralizing antibody (Clone 5A1, BioXcell) or control IgG (clone HRPN, BioXcell) were given i.p. (0.5?mg on postnatal day 14, 0.25?mg on postnatal day 18 and 0.25?mg on postnatal day 22). On subsequent days, three doses of clodronate or control liposomes (Liposoma) 50?µl/injection on postnatal days 15, 19 and 23) were administered i.v. The mice were sacrificed 1 or 11 days after the final clodronate treatment. In control experiments using kidney, we saw a full recovery of a known bone marrow-derived CD11b+F4/80Int macrophage population, but not that of a known fetal-derived CD11bIntF4/80Hi macrophage population, verifying the robustness of the model.
材料和方法文献截图:
