Department of Neurosurgery, R5018 BSRB, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA.
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Transl Stroke Res. 2020 Oct;11(5):1095-1102. doi: 10.1007/s12975-020-00790-4. Epub 2020 Feb 23.
Macrophage phagocytosis plays an important role in hematoma clearance after 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 peri-hematomal 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 enhance hematoma clearance. Understanding the exact roles of MGCs in ICH may reveal novel targets for ICH treatment.
巨核细胞吞噬作用在脑出血（ICH）后血肿清除中起重要作用。本研究在小鼠 ICH 模型中研究了多核巨细胞（MGCs）的特征，MGCs 是一群具有多个核的巨噬细胞。还研究了用 CD47 阻断抗体增加 MGCs 和用氯膦酸脂质体减少 MGCs 的情况。通过自体血注射诱导 ICH。不同组别的雄性成年 C57BL/6 小鼠分别接受：（1）单独 ICH；（2）抗 CD47 阻断抗体或对照 IgG 与 ICH 联合治疗；（3）抗 CD47 抗体联合氯膦酸脂质体或对照脂质体与 ICH 联合治疗。还在雌性小鼠中测试了抗 CD47 抗体对 MGC 形成的影响。在第 3 天或第 7 天收获大脑进行脑组织学检查。ICH 后第 3 天发现许多 MGCs，但第 7 天减少。MGCs 吞噬了许多红细胞，并且血红素加氧酶-1、铁蛋白、YM-1 和 iNOS 阳性。CD47 阻断抗体注射增加了两性围血肿区和血肿内的 MGC 数量。氯膦酸脂质体的共注射减少了血肿核心和血肿周围区的 MGC 数量。总之，MGCs 代表一种具有强吞噬能力的巨噬细胞/小胶质细胞亚型。MGCs 不仅表现出 M2 表型，而且还表现出 M1 表型，并且似乎参与了血红蛋白降解。抗 CD47 抗体增加了 MGCs 的数量，这可能有助于增强血肿清除。了解 MGCs 在 ICH 中的确切作用可能为 ICH 治疗揭示新的靶点。
