Hanada Kentaro
Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan.
Jpn J Infect Dis. 2005 Jun;58(3):131-48.
Sphingolipids are ubiquitous constituents of membrane lipids in eukaryotes. Sphingolipid metabolites modulate various cellular events including proliferation, differentiation, and apoptosis. In addition, sphingolipids, along with cholesterol, form detergent-resistant membrane microdomains, so called 'lipid-rafts', which are implicated in signal transduction and membrane trafficking. Sphingolipids are also relevant to infectious diseases. Various types of pathogens exploit the sphingolipids of host cells as membrane receptors. Sphingolipid metabolites regulate pathogen infection and host defense: for instance, a specific glycosphingolipid acts as an endogenous ligand for activation of natural killer T cells. Lipid-rafts of host cells serve as platforms also for infection signaling and entry of intracellular parasites. Moreover, some post-infectious autoimmune diseases result from production of antibodies cross-reacting with mammalian sphingolipids. Differences in the pathways of sphingolipid metabolism between mammals and non-mammals are good clues for rational development of new anti-infectious disease drugs. This review summarizes recent advances in sphingolipid biology related to infectious diseases.
鞘脂是真核生物膜脂中普遍存在的成分。鞘脂代谢产物调节包括增殖、分化和凋亡在内的各种细胞活动。此外，鞘脂与胆固醇一起形成抗去污剂膜微区，即所谓的“脂筏”，其与信号转导和膜运输有关。鞘脂也与传染病相关。各种病原体利用宿主细胞的鞘脂作为膜受体。鞘脂代谢产物调节病原体感染和宿主防御：例如，一种特定的糖鞘脂作为内源性配体激活自然杀伤T细胞。宿主细胞的脂筏也作为细胞内寄生虫感染信号传导和进入的平台。此外，一些感染后自身免疫性疾病是由与哺乳动物鞘脂发生交叉反应的抗体产生所致。哺乳动物和非哺乳动物鞘脂代谢途径的差异是合理开发新型抗感染药物的良好线索。本综述总结了鞘脂生物学中与传染病相关的最新进展。
