中文摘要：
脑血管中β淀粉样蛋白（β-β）的积累会损害脑淀粉样血管?。–AA）中的血脑屏障（BBB）完整性。巨噬细胞谱系细胞清除 Aβ 并产生疾病缓解介质。在此，我们报告了Aβ40诱导的巨噬细胞衍生的迁移体粘在CAA患者的皮肤活检样本和CAA小鼠模型（Tg-SwDI/B和5xFAD小鼠）的脑组织上的血管上。我们表明，CD5L 被包装在迁移体中并对接到血管中，并且 CD5L 的富集会损害对补体激活的抵抗力。血液中巨噬细胞和膜攻击复合物 （MAC） 的迁移体产生能力增加与患者和 Tg-SwDI/B 小鼠的疾病严重程度相关。值得注意的是，补体抑制治疗可防止 Tg-SwDI/B 小鼠迁移体介导的血脑屏障损伤。因此，我们提出巨噬细胞衍生的迁移体和随之而来的补体激活是 CAA 中潜在的生物标志物和治疗靶点。
英文摘要：
Accumulation of amyloid beta protein (Aβ) in brain vessels damages blood brain barrier (BBB) integrity in cerebral amyloid angiopathy (CAA). Macrophage lineage cells scavenge Aβ and produce disease-modifying mediators. Herein, we report that Aβ40-induced macrophage-derived migrasomes are sticky to blood vessels in skin biopsy samples from CAA patients and brain tissue from CAA mouse models (Tg-SwDI/B and 5xFAD mice). We show that CD5L is packed in migrasomes and docked to blood vessels, and that enrichment of CD5L impairs the resistance to complement activation. Increased migrasome-producing capacity of macrophages and membrane attack complex (MAC) in blood are associated with disease severity in both patients and Tg-SwDI/B mice. Of note, complement inhibitory treatment protects against migrasomes-mediated blood-brain barrier injury in Tg-SwDI/B mice. We thus propose that macrophage-derived migrasomes and the consequent complement activation are potential biomarkers and therapeutic targets in CAA.
论文信息：
论文题目：Macrophage-induced reduction of bacteriophage density limits the efficacy of in vivo pulmonary phage therapy
期刊名称：Nature Communications
时间期卷：14, Article number: 3945 (2023)
在线时间：2023年7月4日
DOI：doi.org/10.1038/s41467-023-39693-x
产品信息：
货号：CP-005-005
规格：5ml+5ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes and Control Liposomes
办事处：Target Technology(靶点科技)
Clodronate Liposomes氯膦酸盐脂质体清除血管周围巨噬细胞（Perivascular macrophages，PVMs
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法：
Peripheral blood monocyte depletion was carried out according to published procedure. Clodronate liposomes (Liposoma, 10?ml/kg, i.p.) was administered to 12-week-old Tg-SwDI/B mice every 3 days to deplete peripheral monocytes/macrophages prior to sacrifice at day 7. Depletion efficacy was confirmed with flow cytometric analysis.
For microglia depletion, PLX5622 was supplied to 12-week-old Tg-SwDI/B mice in the diet at 1200 PPM (1200?mg/kg of chow), starting 7 days prior to sacrifice. Depletion efficacy of was confirmed with immunostaining.
Perivascular macrophage depletion was carried out according to published procedure. 12-week-old Tg-SwDI/B mice were anesthetized with isoflurane and stereotaxically injected with 10?μL of clodronate-containing liposomes into the left lateral ventricle (coordinates from Bregma: anteroposterior, 0.2?mm; mediolateral, 1.2?mm; dorsoventral, 2.3?mm). Animals were sacrificed 7 days later and brains were processed for further analysis. Depletion efficacy of was confirmed with immunostaining.
材料和方法文献截图：
