Clodronate Liposomes氯膦酸盐脂质体和CCR2抗体两者清除单核巨噬细胞

中文摘要：

淋巴丝虫病是非遗传性淋巴水肿的全球性主要原因。我们证明，在小鼠模型中，丝虫 Brugia malayi 在肢体淋巴寄生后诱导淋巴重塑和淋巴引流受损。淋巴功能不全与循环淋巴管生成介质升高有关，包括血管内皮生长因子 C。淋巴功能不全取决于 2 型适应性免疫、白细胞介素-4 受体以及 C-C 趋化因子受体-2 阳性单核细胞和具有促淋巴管生成表型的选择性激活巨噬细胞的募集。第二代四环素类药物口服治疗改善了淋巴功能，而其他类别的抗生素没有显著效果。第二代四环素直接靶向淋巴内皮细胞增殖和改良的 2 型促淋巴管生成巨噬细胞发育。多西环素治疗阻碍了单核细胞募集，抑制了选择性激活的巨噬细胞的极化，并抑制了感染后 T 细胞适应性免疫反应。我们的结果确定了多西环素在丝虫病中抗病作用的作用机制，并支持第二代四环素类药物作为慢性炎症性淋巴水肿的经济实惠、安全的治疗方法的临床评价。

英文摘要：

Lymphatic filariasis is the major global cause of nonhereditary lymphedema. We demonstrate that the filarial nematode Brugia malayi induced lymphatic remodeling and impaired lymphatic drainage following parasitism of limb lymphatics in a mouse model. Lymphatic insufficiency was associated with elevated circulating lymphangiogenic mediators, including vascular endothelial growth factor C. Lymphatic insufficiency was dependent on type 2 adaptive immunity, the interleukin-4 receptor, and recruitment of C-C chemokine receptor-2–positive monocytes and alternatively activated macrophages with a prolymphangiogenic phenotype. Oral treatments with second-generation tetracyclines improved lymphatic function, while other classes of antibiotic had no significant effect. Second-generation tetracyclines directly targeted lymphatic endothelial cell proliferation and modified type 2 prolymphangiogenic macrophage development. Doxycycline treatment impeded monocyte recruitment, inhibited polarization of alternatively activated macrophages, and suppressed T cell adaptive immune responses following infection. Our results determine a mechanism of action for the antimorbidity effects of doxycycline in filariasis and support clinical evaluation of second-generation tetracyclines as affordable, safe therapeutics for lymphedemas of chronic inflammatory origin.

论文信息：

论文题目： Tetracyclines improve experimental lymphatic filariasis pathology by disrupting interleukin-4 receptor–mediated lymphangiogenesis

期刊名称：J Clin Invest.  

时间期卷：2021;131(5):e140853.

在线时间：2021年1月12日

DOI：doi.org/10.1172/JCI140853.

Clodronate Liposomes氯膦酸盐脂质体助力实验性淋巴丝虫病模型巨噬细胞研究，Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于JCI：

Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法：

JCI期刊巨噬细胞清除解决方案

CCR2 and clodronate liposome monocyte/MΦ depletion experiments. Following infection, mice were administered either 20 μg MC-21 rat anti–mouse CCR2 depleting antibody (Matthias Mack, Regensburg University; ref.28) i.p., daily, or 2.5 mg/mL clodronate liposome suspensions (Liposoma) s.c. at BmL3 infection sites every 3 days. Treatment was undertaken for 6 days.