02107nas a2200277   4500000000100000008004100001260001300042653001200055653001800067653002000085653001400105653002600119653001600145653000900161653002500170653001700195653001300212100001500225700001800240700001900258245009000277300001000367490000700377520143100384022001401815       1987                            d  c1987 Mar10aAnimals10aBacteriolysis10aCells, Cultured10aLysosomes10aMacrophage Activation10aMacrophages10aMice10aMycobacterium leprae10aPhagocytosis10aVacuoles1 aSibley L D1 aFranzblau S G1 aKrahenbuhl J L00aIntracellular fate of Mycobacterium leprae in normal and activated mouse macrophages.  a680-50 v553 a<p>Mycobacterium leprae replicates within mononuclear phagocytes, reaching enormous numbers in the macrophage-rich granulomas of lepromatous leprosy. To examine the capability of macrophages to digest M. leprae, we studied the intracellular fate of M. leprae organisms in normal and activated mouse macrophages by using the electron-dense secondary lysosome tracer Thoria Sol. Intracellular M. leprae organisms, surrounded by a characteristic electron-transparent zone, were contained within phagosomal vacuoles of macrophages cultured in vitro for 1 to 6 days. In normal macrophages, a majority of phagosomes containing freshly isolated live M. leprae cells resisted fusion with Thoria Sol-labeled lysosomes. The extent of fusion was not significantly affected by pretreatment of M. leprae with human patient serum high in specific immunoglobulin G and M antibodies. In contrast, a majority of phagosomes containing gamma-irradiated M. leprae cells underwent lysosome fusion in normal macrophages. In addition, increased phagolysosome fusion was observed with live M. leprae-containing phagosomes in macrophages activated with gamma interferon. Increased fusion was associated with an increase in the number of fragmented and damaged bacilli, suggesting that increased digestion followed fusion. This study indicates that activated macrophages may have an increased capacity for clearance of normally resistant M. leprae.</p>  a0019-9567