Clodronate Liposomes氯膦酸鹽脂質體和CCR2抗體兩者清除單核巨噬細胞

中文摘要：

淋巴絲蟲病是非遺傳性淋巴水腫的全球性主要原因。我們證明，在小鼠模型中，絲蟲 Brugia malayi 在肢體淋巴寄生后誘導淋巴重塑和淋巴引流受損。淋巴功能不全與循環(huán)淋巴管生成介質升高有關，包括血管內皮生長因子 C。淋巴功能不全取決于 2 型適應性免疫、白細胞介素-4 受體以及 C-C 趨化因子受體-2 陽性單核細胞和具有促淋巴管生成表型的選擇性激活巨噬細胞的募集。第二代四環(huán)素類藥物口服治療改善了淋巴功能，而其他類別的抗生素沒有顯著效果。第二代四環(huán)素直接靶向淋巴內皮細胞增殖和改良的 2 型促淋巴管生成巨噬細胞發(fā)育。多西環(huán)素治療阻礙了單核細胞募集，抑制了選擇性激活的巨噬細胞的極化，并抑制了感染后 T 細胞適應性免疫反應。我們的結果確定了多西環(huán)素在絲蟲病中抗病作用的作用機制，并支持第二代四環(huán)素類藥物作為慢性炎癥性淋巴水腫的經濟實惠、安全的治療方法的臨床評價。

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.

論文信息：

論文題目： Tetracyclines improve experimental lymphatic filariasis pathology by disrupting interleukin-4 receptor–mediated lymphangiogenesis

期刊名稱：J Clin Invest.  

時間期卷：2021;131(5):e140853.

在線時間：2021年1月12日

DOI：doi.org/10.1172/JCI140853.

Clodronate Liposomes氯膦酸鹽脂質體助力實驗性淋巴絲蟲病模型巨噬細胞研究，Liposoma巨噬細胞清除劑Clodronate Liposomes見刊于JCI：

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質體的材料和方法：

JCI期刊巨噬細胞清除解決方案

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.