Utermöhlen Olaf, Herz Jasmin, Schramm Michael, Krönke Martin
Institute for Medical Microbiology, Immunology and Hygiene, Medical Center, University of Cologne, Goldenfelsstrasse 19-21, 50935 Cologne, Germany.
Immunobiology. 2008;213(3-4):307-14. doi: 10.1016/j.imbio.2007.10.016. Epub 2007 Dec 31.
Acid sphingomyelinase (ASMase) has been implemented in cellular signaling mainly because its reaction product, ceramide, has been assumed to be a mediator within signaling pathways. Our studies of three independent infection systems show that ASMase is required for phago-lysosomal fusion in macrophages infected with Listeria monocytogenes, for exocytosis of secretory lysosomes by lymphocytic choriomeningitis virus-specific cytotoxic T cells, and for generation of multinucleated giant cells in granuloma of mice infected with Mycobacterium avium. Because of its neutral lipid nature, ceramide is confined to the membranes of phagosomes and lysosomes or the extracellular leaflet of the plasma membrane. In light of the biochemical and biophysical properties of ceramide, we provide a model suggesting that ASMase regulates select vesicular fusion processes by modifying the steric conformation of cellular membranes.
酸性鞘磷脂酶（ASMase）已被应用于细胞信号传导，主要是因为其反应产物神经酰胺被认为是信号通路中的一种介质。我们对三个独立感染系统的研究表明，ASMase对于单核细胞增生李斯特菌感染的巨噬细胞中的吞噬溶酶体融合、淋巴细胞性脉络丛脑膜炎病毒特异性细胞毒性T细胞分泌溶酶体的胞吐作用以及鸟分枝杆菌感染的小鼠肉芽肿中多核巨细胞的形成是必需的。由于神经酰胺的中性脂质性质，它局限于吞噬体和溶酶体的膜或质膜的细胞外小叶。鉴于神经酰胺的生化和生物物理性质，我们提供了一个模型，表明ASMase通过改变细胞膜的空间构象来调节特定的囊泡融合过程。
