GSL-Enriched Membrane Microdomains in Innate Immune Responses
GSL-Enriched Membrane Microdomains in Innate Immune Responses
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DOI：
10.1007/s00005-013-0221-6
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发表时间：
2013-02
影响因子：
3.2
通讯作者：
H. Nakayama;H. Ogawa;K. Takamori;K. Iwabuchi
中科院分区：
文献类型：
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作者：
H. Nakayama;H. Ogawa;K. Takamori;K. Iwabuchi
许多病原体靶向鞘糖脂（GSL），其与胆固醇、GPI锚定蛋白和各种信号分子一起聚集在宿主细胞膜上以形成富含GSL的膜微结构域（脂筏）。因此，这些富含GSL的膜微区可能参与宿主-病原体相互作用。先天性免疫应答由病原体与吞噬细胞（如嗜中性粒细胞、巨噬细胞和树突细胞）的缔合触发。吞噬细胞表达多种模式识别受体（PRR），这些受体感知入侵的微生物并触发病原体特异性信号传导。PRR可以识别微生物上表达的高度保守的病原体相关分子模式。GSL乳糖神经酰胺（LacCer，CDw 17）主要表达于人成熟中性粒细胞的质膜上，与Src家族酪氨酸激酶林恩共同形成膜微区，与包括白色念珠菌在内的多种微生物结合。这些富含LacCer的膜微区可以介导超氧化物的产生、迁移和吞噬作用，表明LacCer在先天免疫中起PRR的作用。此外，富含GSL的膜微区与膜蛋白（如生长因子受体）的相互作用在介导这些蛋白质的生理特性中是重要的。同样，我们最近发现富含LacCer的膜微区与CD 11b/CD 18（Mac-1、CR 3或αMβ2-整联蛋白）之间的相互作用对于非调理微生物的中性粒细胞吞噬作用具有重要意义。本文综述了乳酸铈富集膜微区的功能作用及其与CD 11b/CD 18的相互作用。
Many pathogens target glycosphingolipids (GSLs), which, together with cholesterol, GPI-anchored proteins, and various signaling molecules, cluster on host cell membranes to form GSL-enriched membrane microdomains (lipid rafts). These GSL-enriched membrane microdomains may therefore be involved in host–pathogen interactions. Innate immune responses are triggered by the association of pathogens with phagocytes, such as neutrophils, macrophages and dendritic cells. Phagocytes express a diverse array of pattern-recognition receptors (PRRs), which sense invading microorganisms and trigger pathogen-specific signaling. PRRs can recognize highly conserved pathogen-associated molecular patterns expressed on microorganisms. The GSL lactosylceramide (LacCer, CDw17), which binds to various microorganisms, includingCandida albicans, is expressed predominantly on the plasma membranes of human mature neutrophils and forms membrane microdomains together with the Src family tyrosine kinase Lyn. These LacCer-enriched membrane microdomains can mediate superoxide generation, migration, and phagocytosis, indicating that LacCer functions as a PRR in innate immunity. Moreover, the interactions of GSL-enriched membrane microdomains with membrane proteins, such as growth factor receptors, are important in mediating the physiological properties of these proteins. Similarly, we recently found that interactions between LacCer-enriched membrane microdomains and CD11b/CD18 (Mac-1, CR3, or αMβ2-integrin) are significant for neutrophil phagocytosis of non-opsonized microorganisms. This review describes the functional role of LacCer-enriched membrane microdomains and their interactions with CD11b/CD18.