Collins H L, Schaible U E, Ernst J D, Russell D G
Department of Molecular Microbiology, Washington University School of Medicine, St Louis MO 63110, USA.
J Cell Sci. 1997 Jan;110 ( Pt 2):191-200. doi: 10.1242/jcs.110.2.191.
The eukaryotic intracellular pathogen Leishmania mexicana resides inside macrophages contained within a membrane bound parasitophorous vacuole which, as it matures, acquires the characteristics of a late endosomal compartment. This study reports the selectivity of fusion of this compartment with other particle containing vacuoles. Phagosomes containing zymosan or live Listeria monocytogenes rapidly fused with L. mexicana parasitophorous vacuoles, while those containing latex beads or heat killed L. monocytogenes failed to do so. Fusigenicity of phagosomes was not primarily dependent on the receptor utilized for ingestion, as opsonization with defined ligands could not overcome the exclusion of either latex beads or heat killed organisms. However modulation of intracellular pH by pharmacological agents such as chloroquine and ammonium chloride increased delivery of live Listeria and also induced transfer of previously excluded particles. The absence of fusion correlated with the acquisition of annexin I, a putative lysosomal targeting, molecule, on the phagosome membrane. We propose that the acquisition of cellular membrane constituents such as annexin I during phagosome maturation can ultimately direct the fusion pathway of the vesicles formed and have described a model system to further document changes in vesicle fusigenicity within cells.
真核细胞内病原体墨西哥利什曼原虫寄生于巨噬细胞内的膜结合寄生泡中，随着寄生泡的成熟，它会获得晚期内体区室的特征。本研究报告了该区室与其他含颗粒泡融合的选择性。含有酵母聚糖或活单核细胞增生李斯特菌的吞噬体迅速与墨西哥利什曼原虫寄生泡融合，而含有乳胶珠或热灭活单核细胞增生李斯特菌的吞噬体则不能。吞噬体的融合能力并非主要取决于用于摄取的受体，因为用特定配体进行调理不能克服乳胶珠或热灭活生物体的排斥。然而，用氯喹和氯化铵等药物调节细胞内pH值可增加活李斯特菌的传递，并诱导先前被排斥颗粒的转移。融合的缺失与吞噬体膜上假定的溶酶体靶向分子膜联蛋白I的获得有关。我们提出，吞噬体成熟过程中细胞膜成分如膜联蛋白I的获得最终可指导所形成囊泡的融合途径，并描述了一个模型系统以进一步记录细胞内囊泡融合能力的变化。
