Involvement of glycosphingolipid-enriched lipid rafts in inflammatory responses
Involvement of glycosphingolipid-enriched lipid rafts in inflammatory responses
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DOI：
10.2741/4312
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发表时间：
2015-01-01
影响因子：
3.1
通讯作者：
Iwabuchi, Kazuhisa
中科院分区：
文献类型：
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作者：
Iwabuchi, Kazuhisa
鞘糖脂(GSLS)是由疏水性神经酰胺和亲水性糖基组成的膜成分。GSLS与细胞膜中的胆固醇聚集形成富含GSL的脂筏。生化分析表明，富含GSL的脂筏含有多种转导分子，包括Src家族激酶。在GSLs中，乳糖基神经酰胺(LacCer，CDw17)可与多种微生物结合，在人吞噬细胞质膜上高表达，并形成含有Src家族酪氨酸激酶Lyn的脂筏。富含LacCer的脂筏介导免疫和炎症反应，包括超氧化物生成、趋化作用和非调理吞噬作用。因此，富含LacCer的膜微域被认为具有模式识别受体(PRRs)的功能，识别微生物上表达的病原体相关分子模式(PAMPs)。LacCer还作为CD11b/CD18-整合素(αM/β2-整合素，CR3，Mac-1)介导的信号转导分子，并与几个关键的细胞过程有关。LacCer招募PCKα/epsilon和磷脂酶A2来刺激人单核细胞表达PECAM-1及其与内皮细胞的黏附，并调节细胞表面的β1整合素聚集和内吞作用。该综述描述了富含LacCer的脂筏的组织和炎症相关功能。
Glycosphingolipids (GSLs) are membrane components consisting of hydrophobic ceramide and hydrophilic sugar moieties. GSLs cluster with cholesterol in cell membranes to form GSL-enriched lipid rafts. Biochemical analyses have demonstrated that GSL-enriched lipid rafts contain several kinds of transducer molecules, including Src family kinases. Among the GSLs, lactosylceramide (LacCer, CDw17) can bind to various microorganisms, is highly expressed on the plasma membranes of human phagocytes, and forms lipid rafts containing the Src family tyrosine kinase Lyn. LacCer-enriched lipid rafts mediate immunological and inflammatory reactions, including superoxide generation, chemotaxis, and non-opsonic phagocytosis. Therefore, LacCer-enriched membrane microdomains are thought to function as pattern recognition receptors (PRRs), which recognize pathogen-associated molecular patterns (PAMPs) expressed on microorganisms. LacCer also serves as a signal transduction molecule for functions mediated by CD11b/CD18-integrin (alpha M/beta 2-integrin, CR3, Mac-1), as well as being associated with several key cellular processes. LacCer recruits PCK alpha/epsilon and phospholipase A2 to stimulate PECAM-1 expression in human monocytes and their adhesion to endothelial cells, as well as regulating beta 1-integrin clustering and endocytosis on cell surfaces. This review describes the organizational and inflammation-related functions of LacCer-enriched lipid rafts.