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氣管內給藥Clodronate liposomes會清除DC細胞嗎?

更新時間:2026-02-10   點擊次數:144次

Clodronate liposomes 由包封在磷脂雙分子層脂質體內的氯磷酸鹽組成,可以被巨噬細胞選擇性攝取。在巨噬細胞溶酶體內,磷酸酶逐步釋放脂質體內的氯磷酸鹽,使其在細胞內累積。當達到閾值濃度時,該累積會導致巨噬細胞不可逆損傷并誘導凋亡,使 clodronate liposomes 成為研究巨噬細胞清除及免疫調控的重要工具。Clodronate liposomes是荷蘭免疫學家Nico Van Rooijen在上世紀90年代發明開發。Nico Van Rooijen為Clodronate liposomes清除巨噬細胞做了很多原創性,基礎性的工作,發表了大量文獻。

當使用荷蘭Liposoma的巨噬細胞清除劑Clodronate liposomes氯膦酸鹽脂質體,氣管給藥清除肺部肺泡巨噬細胞細胞時,巨噬細胞清除劑氯膦酸鹽脂質體Clodronate liposomes會清除DC細胞嗎?肺泡巨噬細胞和DC細胞都是CD11c陽性,根據如下文獻的研究,氣管內給藥Clodronate liposomes不會清除DC細胞。

文獻題目:Murine alveolar macrophages limit replication of vaccinia virus

動物品系:129 Ev/Sv小鼠

給藥方法:氣管注射100 uL


原文描述:

Some populations of dendritic cells may be depleted by clodronate liposomes (Leenen et al., 1998), although effects of this treatment on lung dendritic cells remain poorly defined. We quantified numbers of dendritic cells in lungs of mice treated with clodronate or control saline liposomes. Clodronate liposomes did not affect total numbers of CD11c(+), MHC class II(+) dendritic cells in the lung interstitium as compared with control liposomes. In both groups, dendritic cells comprised ≈ 0.8% of total cells in the lungs, which is consistent with our previous data from untreated mice. Because antigen presenting cells such as dendritic cells and macrophages migrate to regional lymph nodes to initiate adaptive immunity, we also quantified numbers of these cell types in the tracheobronchial lymph node of mice 2 days after injection of liposomes. There were no significant differences between clodronate and saline control mice in numbers or percentages of CD11c(+), MHC class II(+) dendritic cells, Mac-3(+) macrophages, or ERMP-20(+) late monocyte progenitors in these lymph nodes (data not shown). Furthermore, numbers or percentages of dendritic cells and macrophages in peripheral blood, as determined by these same cell surface markers, did not differ between mice 2 days following treatment with clodronate or saline liposomes (data not shown). Collectively, these data demonstrate that intratracheal administration of clodronate liposomes depleted only alveolar macrophages.


原文翻譯:


某些群體的樹突狀細胞可能會被氯膦酸鹽脂質體消耗(Leenen 等,1998),盡管這種處理對肺樹突狀細胞的影響尚不清楚。我們對接受氯膦酸鹽脂質體或對照生理鹽水脂質體處理的小鼠肺部樹突狀細胞數量進行了量化。與對照脂質體相比,氯膦酸鹽脂質體并未影響肺間質中 CD11c(+ )、MHC II(+ ) 樹突狀細胞的總數。在兩組中,樹突狀細胞約占肺總細胞的 0.8%,這與我們之前在未經處理的小鼠中獲得的數據一致。由于抗原呈遞細胞如樹突狀細胞和巨噬細胞會遷移至區域淋巴結以啟動適應性免疫,我們還量化了脂質體注射后 2 天小鼠氣管支氣管淋巴結中這些細胞類型的數量。氯膦酸鹽脂質體與生理鹽水對照小鼠在氣管支氣管淋巴結中 CD11c(+ )、MHC II( +) 樹突狀細胞、Mac-3(+ ) 巨噬細胞或 ERMP-20( +) 晚期單核細胞前體的數量或百分比之間沒有顯著差異(數據未顯示)。此外,通過這些相同的細胞表面標志確定的外周血中樹突狀細胞和巨噬細胞的數量或百分比,在氯膦酸鹽脂質體或生理鹽水脂質體處理后 2 天的小鼠之間也無差異(數據未顯示)??傮w而言,這些數據表明,氣管內給予氯膦酸鹽脂質體僅能消耗肺泡巨噬細胞。


參考文獻:

P. Leenen et al., Heterogeneity of mouse spleen dendritic cells: in vivo phagocytic activity, expression of macrophage markers, and subpopulation turnover. J. Immunol., 160 (5) (1998), pp. 2166-2173.


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