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Ammonium chloride, an inhibitor of phagosome-lysosome fusion in macrophages, concurrently induces phagosome-endosome fusion, and opens a novel pathway: studies of a pathogenic mycobacterium and a nonpathogenic yeast.
氯化铵是巨噬细胞中吞噬体-溶酶体融合的抑制剂,同时诱导吞噬体-内体融合,并开辟了一条新途径: 致病性分枝杆菌和非致病性酵母的研究。

摘要

The weak base ammonium chloride has been previously reported to inhibit lysosomal movements and phagosome-lysosome (Ph-L) fusion in cultured mouse macrophages (M phi), thus reducing delivery, to an intraphagosomal infection, of endocytosed solutes that have concentrated in secondary lysosomes. We have now addressed the question, whether NH4Cl might affect any direct interaction (if it exists) between such infection phagosomes and earlier, nonlysosomal compartments of the endocytic pathway, i.e., solute-containing endosomes. The phagosomes studied were formed after ingestion of the mouse pathogen Mycobacterium microti and the nonpathogenic yeast Saccharomyces cerevisiae; and the endosomes were formed after nonreceptor-mediated endocytosis of electronopaque and fluorescent soluble markers. By electron microscopy, survey of the cell profiles of M phi that had been treated with 10 mM NH4Cl so that Ph-L fusion was prevented, and that displayed many ferritin-labeled endosomes, revealed numerous examples of the fusion of electronlucent endosomes, revealed numerous examples of the fusion of electronlucent vesicles with phagosomes, whether containing M. microti bacilli or S. cerevisiae yeasts. Fusion was recognized by transfer of label and by morphological evidence of fusion in progress. The fusing vesicles were classed as endosomes, not NH4Cl-lysosomes, by their appearance and provenance, and because lysosome participation was excluded by the concurrent, NH4Cl-caused block of Ph-L fusion and associated lysosomal stasis. No evidence of such phagosome-endosome (Ph-E) fusion was observed in profiles from M phi treated with chloroquine, nor in those from normal, untreated M phi. NH4Cl-treated living M phi that had ingested yeasts at 37 degrees C, followed by endocytosis of lucifer yellow at 17 degrees C (to accumulate labeled endosomes and postpone label passing to lysosomes), were then restored to 37 degrees C. Fluorescence microscopy showed that as many as half of the yeast phagosomes (previously unlabeled) rapidly became colored. We inferred that this transfer was from endosomes (by Ph-E fusion) because Ph-L passage was blocked (by the NH4Cl). We conclude that NH4Cl induces Ph-E fusion at the same time as it suppressed Ph-L fusion. We discuss the mechanisms of these concurrent effects and suggest that they are independent; and we consider the implications of NH4Cl opening a direct route for endocytosed molecules to reach an intraphagosomal infection without involving lysosomes.

译文

之前报道过弱碱氯化铵可以抑制培养的小鼠巨噬细胞 (M phi) 中的溶酶体移动和吞噬体-溶酶体 (Ph-L) 的融合,从而减少递送, 在第二个溶酶体中集中的胞内溶解的溶质的感染。我们现在已经解决了这个问题,NH4Cl 是否会影响这种感染吞噬体和内吞途径的早期非溶酶体区室,即含溶质的内体之间的任何直接相互作用 (如果存在的话)。研究的吞噬体是在摄入小鼠病原体微分枝杆菌和非致病性酵母酿酒酵母后形成的; 而内体是在非受体介导的电性和荧光可溶性标记的内吞后形成的。通过电子显微镜,对用 10 毫米 NH4Cl 处理过的 M phi 的细胞轮廓的调查,以防止 Ph-L 融合,并显示许多铁蛋白标记的内体, 揭示了大量电晶体内体融合的例子,揭示了大量电晶体囊泡与吞噬体融合的例子,是否含有 M.microti 杆菌或 S.cerevisiae 酵母。通过标记转移和正在进行的融合的形态学证据来识别融合。融合囊泡根据其外观和来源被归类为内体,而不是 NH4Cl-lysosomes,并且因为溶酶体的参与被同时发生的、 NH4Cl-caused 的 Ph-L 融合阻滞和相关的溶酶体停滞所排除。在用氯喹处理的 M phi 的剖面中,也没有观察到这种吞噬体-内体 (Ph-E) 融合的证据,也没有观察到正常的未处理的 M phi 的剖面中。NH4Cl-treated 在 37 摄氏度时摄入了酵母的活 M phi,随后在 17 摄氏度时内吞路西法黄色 (积累标记的内体并推迟标记传递到溶酶体), 然后恢复到 37 摄氏度荧光显微镜显示多达一半的酵母吞噬体 (以前未标记)迅速变成有色。我们推断这种转移来自内体 (通过 Ph-E 融合),因为 Ph-L 通道被阻断 (通过 NH4Cl)。我们得出结论,NH4Cl 在抑制 Ph-L 融合的同时诱导 Ph-E 融合。我们讨论了这些并发效应的机制,并建议它们是独立的; 我们考虑了 NH4Cl 的含义,它为胞内分子打开了一条直接的途径,使其到达体内感染,而不涉及溶酶体。

Ammonium chloride

呼吸 祛痰合剂的主要成分之一 实验材料
概述  :  

氯化铵是祛痰合剂的主要成分之一。本品是无机盐类或偏酸性盐类。妊娠分类:B。 指征与剂量 痰:①本品一般不单独应用,常见于其他镇咳祛痰药组成的复方制剂中。适用于急、慢性支气管炎痰液黏稠难以咳岀的患者。②酸化体液:治疗碱血症。③酸化尿液:可以促进某些碱性药物的排泄,也可使必须在酸性环境中发挥药效的药物(如乌洛托品)产生作用。 口服:祛痰时,成人0.3~0.6g,tid。 酸化体液或尿液时,成

Ammonium   英 /əˈməʊniəm/   美  /əˈmoʊniəm/ 

释    义   n. [无化] 铵;氨盐基

例    句   But the presence of ammonium in Greenland ice cores at both times is accepted by scientists. 但在格陵兰的冰核同时代发现氨的存在得到科学家的认同。

 

Chloride   /ˈklɔːraɪd/ 

释    义   n. 氯化物

同根词   chlorination n. 氯化作用,加氯消毒

               chlorinate vt.用氯消毒;使氯化;使氯发生作用

例    句   So, which atom would you expect to be in the center of a Lewis structure for thionylchloride? 那么,大家认为哪个原子应该在亚硫酰氯的路易斯结构的中心位置呢?

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