Clodronate liposomes 由包封在磷脂雙分子層脂質(zhì)體內(nèi)的氯磷酸鹽組成,可以被巨噬細(xì)胞選擇性攝取。在巨噬細(xì)胞溶酶體內(nèi),磷酸酶逐步釋放脂質(zhì)體內(nèi)的氯磷酸鹽,使其在細(xì)胞內(nèi)累積。當(dāng)達(dá)到閾值濃度時(shí),該累積會(huì)導(dǎo)致巨噬細(xì)胞不可逆損傷并誘導(dǎo)凋亡,使 clodronate liposomes 成為研究巨噬細(xì)胞清除及免疫調(diào)控的重要工具。Clodronate liposomes是荷蘭免疫學(xué)家Nico Van Rooijen在上世紀(jì)90年代發(fā)明開發(fā)。Nico Van Rooijen為Clodronate liposomes清除巨噬細(xì)胞做了很多原創(chuàng)性,基礎(chǔ)性的工作,發(fā)表了大量文獻(xiàn)。
當(dāng)使用荷蘭Liposoma的巨噬細(xì)胞清除劑Clodronate liposomes氯膦酸鹽脂質(zhì)體,氣管給藥清除肺部肺泡巨噬細(xì)胞細(xì)胞時(shí),巨噬細(xì)胞清除劑氯膦酸鹽脂質(zhì)體Clodronate liposomes會(huì)清除DC細(xì)胞嗎?肺泡巨噬細(xì)胞和DC細(xì)胞都是CD11c陽(yáng)性,根據(jù)如下文獻(xiàn)的研究,氣管內(nèi)給藥Clodronate liposomes不會(huì)清除DC細(xì)胞。
文獻(xiàn)題目:Murine alveolar macrophages limit replication of vaccinia virus
動(dòng)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(xì)胞可能會(huì)被氯膦酸鹽脂質(zhì)體消耗(Leenen 等,1998),盡管這種處理對(duì)肺樹突狀細(xì)胞的影響尚不清楚。我們對(duì)接受氯膦酸鹽脂質(zhì)體或?qū)φ丈睇}水脂質(zhì)體處理的小鼠肺部樹突狀細(xì)胞數(shù)量進(jìn)行了量化。與對(duì)照脂質(zhì)體相比,氯膦酸鹽脂質(zhì)體并未影響肺間質(zhì)中 CD11c(+ )、MHC II(+ ) 樹突狀細(xì)胞的總數(shù)。在兩組中,樹突狀細(xì)胞約占肺總細(xì)胞的 0.8%,這與我們之前在未經(jīng)處理的小鼠中獲得的數(shù)據(jù)一致。由于抗原呈遞細(xì)胞如樹突狀細(xì)胞和巨噬細(xì)胞會(huì)遷移至區(qū)域淋巴結(jié)以啟動(dòng)適應(yīng)性免疫,我們還量化了脂質(zhì)體注射后 2 天小鼠氣管支氣管淋巴結(jié)中這些細(xì)胞類型的數(shù)量。氯膦酸鹽脂質(zhì)體與生理鹽水對(duì)照小鼠在氣管支氣管淋巴結(jié)中 CD11c(+ )、MHC II( +) 樹突狀細(xì)胞、Mac-3(+ ) 巨噬細(xì)胞或 ERMP-20( +) 晚期單核細(xì)胞前體的數(shù)量或百分比之間沒有顯著差異(數(shù)據(jù)未顯示)。此外,通過(guò)這些相同的細(xì)胞表面標(biāo)志確定的外周血中樹突狀細(xì)胞和巨噬細(xì)胞的數(shù)量或百分比,在氯膦酸鹽脂質(zhì)體或生理鹽水脂質(zhì)體處理后 2 天的小鼠之間也無(wú)差異(數(shù)據(jù)未顯示)??傮w而言,這些數(shù)據(jù)表明,氣管內(nèi)給予氯膦酸鹽脂質(zhì)體僅能消耗肺泡巨噬細(xì)胞。
參考文獻(xiàn):
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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