Response by Hua et al to Letter Regarding Article, "Enhancement of Hematoma Clearance With CD47 Blocking Antibody in Experimental Intracerebral Hemorrhage".
Response by Hua et al to Letter Regarding Article, "Enhancement of Hematoma Clearance With CD47 Blocking Antibody in Experimental Intracerebral Hemorrhage".
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DOI：
10.1161/strokeaha.119.026620
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发表时间：
2019-07
期刊：
影响因子：
8.3
通讯作者：
Y. Hua;R. Keep;G. Xi
中科院分区：
文献类型：
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作者：
Y. Hua;R. Keep;G. Xi
回应：我们感谢陈博士等人对我们文章的兴趣。我们已经证明，CD 47阻断抗体可以通过激活小胶质细胞/巨噬细胞来增强血肿清除，并改善脑出血（ICH）小鼠模型的功能结局。他们的评论提出了几个重要的问题，包括小胶质细胞/巨噬细胞极化和潜在的吞噬作用的神经元表达CD 47，如果封闭抗体。了解小胶质细胞/巨噬细胞极化在血肿清除中的作用非常重要，因为血肿清除是ICH的治疗目标。应该注意的是，小胶质细胞/巨噬细胞表型对脑损伤/恢复的影响是复杂和有争议的。M1和M2表型对脑疾病（包括ICH）后的脑损伤都有有害和有益的影响。为了了解小胶质细胞/巨噬细胞极化在脑出血后脑损伤和恢复中的确切作用，应进行体内和体外实验来评估在有或没有CD 47阻断抗体的情况下脑出血后M1和M2极化的时间过程。我们完全同意Dr Chen等人的观点，即使用封闭抗体靶向红细胞CD 47并增强血肿清除也可能因神经元CD 47表达而产生不良副作用。我们之前已经发现脑出血后血肿周围CD 47增加，包括神经元。在当前研究中，封闭抗体与血肿一起给予，限制了实质暴露。然而，在癌症领域，研究人员已经研究了靶向CD 47和表皮生长因子受体的双特异性抗体，以更特异地靶向癌细胞，特别是避免红细胞吞噬。类似的方法应该可以帮助特异性靶向红细胞CD 47，即靶向CD 47和另一种红细胞特异性膜蛋白的双特异性蛋白。我们同意Dr Chen等人的观点，即靶向CD 47是一种有吸引力的ICH治疗策略。它可能是血肿清除的辅助治疗，我们将继续探讨靶向CD 47的利弊。
In Response: We thank Dr Chen et al for their interest in our article. We have demonstrated that CD47 blocking antibody can enhance hematoma clearance through activation of microglia/macrophages and improve functional outcomes in a mouse model of intracerebral hemorrhage (ICH). Their comments raised several important issues, including microglia/macrophage polarization and potential phagocytosis of neurons expressing CD47 if the blocking antibody is given. It is important to understand the role in microglia/macrophage polarization in hematoma removal because hematoma clearance is a therapeutic target in ICH. It should be noted that the effects of microglia/macrophage phenotypes on brain injury/ recovery are complex and controversial. Both M1 and M2 phenotypes have harmful and beneficial effects on brain injury after brain disorders, including ICH. To understand the precise role of microglia/macrophage polarization in brain injury and recovery after ICH, in vivo and in vitro experiments should be performed to evaluate the time course of M1 and M2-polarization after ICH with or without CD47 blocking antibody. We totally agree with Dr Chen et al that using a blocking antibody to target erythrocyte CD47 and enhance hematoma clearance might also have an adverse side effect due to neuronal CD47 expression. We have previously found an increase in perihematomal CD47, including in neurons, after ICH. In the current study, the blocking antibody was given with the hematoma, limiting parenchymal exposure. However, in the cancer field, researchers have examined a bispecific antibody targeting CD47 and epidermal growth factor receptor to more specifically target cancer cells and, in particular, avoid erythrocyte phagocytosis. A similar approach should be possible to help specifically target erythrocyte CD47, that is, a bispecific protein targeting CD47 and another erythrocyte specific membrane protein. We concur with Dr Chen et al that targeting CD47 is an attractive therapeutic strategy for ICH. It might be an adjunct therapy for hematoma evacuation, and we continue to explore the pros and cons of targeting CD47.