Multinucleated Giant Cells in Experimental Intracerebral Hemorrhage.
Multinucleated Giant Cells in Experimental Intracerebral Hemorrhage.
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DOI：
10.1007/s12975-020-00790-4
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发表时间：
2020-10
影响因子：
6.9
通讯作者：
Xi G
中科院分区：
文献类型：
--
作者：
Wei J;Wang M;Jing C;Keep RF;Hua Y;Xi G
巨噬细胞吞噬作用在脑出血（ICH）中的血肿清除中发挥重要作用。本研究在小鼠 ICH 模型中检查了多核巨细胞 (MGC)（一组具有多个核的巨噬细胞）的特征。还检查了 MGC 是否可以通过 CD47 阻断抗体处理而增加，并通过氯膦酸盐脂质体处理而减少。通过自体血注射诱导ICH。不同组中的雄性成年C57BL/6小鼠有：1）仅ICH； 2) 使用抗CD47阻断抗体或对照IgG进行ICH； 3)使用抗CD47抗体与氯膦酸盐脂质体或对照脂质体组合的ICH。还在女性中测试了抗 CD47 抗体对 MGC 形成的影响。在第3天或第7天收获大脑用于脑组织学分析。 ICH后第3天发现许多MGC，但在第7天减少。MGC吞噬许多红细胞，并且血红素加氧酶-1、铁蛋白、YM-1和iNOS呈阳性。 CD47 阻断抗体注射增加了男女血肿周围区和血肿中的 MGC 数量。氯膦酸盐脂质体的共同注射耗尽了血肿核心和血肿周围区域的 MGC。总之，MGC 代表了具有强吞噬能力的巨噬细胞/小胶质细胞亚型。 MGC 不仅表现出 M2 表型，还表现出 M1 表型，并且似乎参与血红蛋白降解。抗 CD47 抗体增加了 MGC 的数量，这可能有助于增强血肿清除。了解 MGC 在 ICH 中的确切作用可能会揭示 ICH 治疗的新靶点。
Macrophage phagocytosis plays an important role hematoma clearance in intracerebral hemorrhage (ICH). This study examined the characteristics of multinucleated giant cells (MGCs), a group of macrophages with multiple nuclei, in a mouse ICH model. Whether MGCs could be increased by treatment with a CD47 blocking antibody and decreased by treatment with clodronate liposomes were also examined. ICH was induced via autologous blood injection. Male adult C57BL/6 mice in different groups had: 1) ICH alone; 2) ICH with anti-CD47 blocking antibody or control IgG; and 3) ICH with anti-CD47 antibody combined with clodronate liposomes or control liposomes. The effect of anti-CD47 antibody on MGC formation was also tested in females. Brains were harvested at days 3 or 7 for brain histology. Many MGCs were found at day 3 post-ICH, but were reduced at day 7. MGCs phagocytosed many red blood cells and were heme oxygenase-1, ferritin, YM-1 and iNOS positive. CD47 blocking antibody injection increased MGC numbers in the perihematomal zone and in the hematoma in both sexes. Co-injection of clodronate liposomes depleted MGCs in both the hematoma core and the peri-hematomal area. In conclusion, MGCs represent a macrophage/microglia subtype with strong phagocytosis capacity. MGCs exhibited not only an M2 but also an M1 phenotype and appeared involved in hemoglobin degradation. Anti-CD47 antibody boosted the number of MGCs, which may contribute to enhanced hematoma clearance. Understanding the exact roles of MGCs in ICH may reveal novel targets for ICH treatment.
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影响因子：
7.1
作者：
Bachstetter AD;Van Eldik LJ;Schmitt FA;Neltner JH;Ighodaro ET;Webster SJ;Patel E;Abner EL;Kryscio RJ;Nelson PT
通讯作者：
Nelson PT
影响因子：
6.9
作者：
Liu H;Hua Y;Keep RF;Xi G
通讯作者：
Xi G
影响因子：
2.8
作者：
CHAMBERS, TJ;SPECTOR, WG
通讯作者：
SPECTOR, WG
影响因子：
168.9
作者：
Hanley, Daniel F.;Thompson, Richard E.;Awad, Issam A.
通讯作者：
Awad, Issam A.
影响因子：
3.6
作者：
McNally, AK;Anderson, JM
通讯作者：
Anderson, JM