AMMONIA INHIBITS PHAGOSOME-LYSOSOME FUSION IN MACROPHAGES
AMMONIA INHIBITS PHAGOSOME-LYSOSOME FUSION IN MACROPHAGES
复制标题
DOI：
10.1038/286079a0
复制
发表时间：
1980-01-01
期刊：
影响因子：
64.8
通讯作者：
YOUNG, MR
中科院分区：
文献类型：
--
作者：
GORDON, AH;DARCYHART, P;YOUNG, MR
当包括许多微生物在内的异物被培养的巨噬细胞摄入时，它们被包裹在吞噬体中，溶酶体通常与吞噬体融合，然后将它们的酶和其他内容物排放到产生的吞噬溶酶体中。然而，这种融合在某些病原体吞噬后减少或消失，特别是结核分枝杆菌和刚地弓形虫。假设不融合是由于噬菌体内微生物的主动抑制，那么抑制剂的鉴定应该能澄清溶酶体的控制机制。有研究表明，毒性结核中存在的强酸性硫化物，与其他具有多阴离子结构特征的物质一样，本身可以阻断吞噬体-溶酶体融合（P-LF） 3-5，这可能导致溶酶体对摄入的结核菌产生负反应4。我们在这里报告了另一种可能性，基于结核杆菌培养滤液在传统类型定义的培养基上抑制含酵母的吞噬体融合；我们表明，这种滤液的氨含量足以说明它们的效果。这种对融合的抑制似乎是迄今尚未认识到的添加氨的细胞内结果，与某些亲脂胺产生的增强形成鲜明对比。
When foreign bodies, including many microorganisms, are ingested by cultured macrophages, they become enclosed in phagosomes, with which lysosomes usually fuse and then discharge their enzymes and other contents into the resulting phagolysosomes. Such fusion is, however, diminished or absent after the phagocytosis of some pathogens, notablyMycobacterium tuberculosis1andToxoplasma gondii2. Assuming that the nonfusion is due to active inhibition by the intraphagosomal microbe, identification of an inhibitor should clarify the lysosomal control mechanism. It has been suggested that strongly acidic sulphatides present in virulenttuberculosis, which, like other substances with polyanionic structural features, can themselves block phagosome–lysosome fusion (P-LF)3–5, may contribute to the negative lysosome response to ingested tubercle bacilli4. We report here another possibility, based on inhibition of fusion of yeast-containing phagosomes by filtrates from cultures of tubercle bacilli on traditional-type defined media; we show that the ammonia content of such filtrates is sufficient to account for their effect. This inhibition of fusion seems to be an hitherto unrecognized intracellular consequence of added ammonia, in striking contrast to the enhancement produced by some lipophilic amines3.