Role of Ceramide from Glycosphingolipids and Its Metabolites in Immunological and Inflammatory Responses in Humans.
Role of Ceramide from Glycosphingolipids and Its Metabolites in Immunological and Inflammatory Responses in Humans.
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DOI：
10.1155/2015/120748
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发表时间：
2015
影响因子：
4.6
通讯作者：
Takamori K
中科院分区：
文献类型：
--
作者：
Iwabuchi K;Nakayama H;Oizumi A;Suga Y;Ogawa H;Takamori K
鞘糖脂（Glycosphingolipids，GSL）是由疏水性神经酰胺和亲水性糖链组成。GSL与Src家族激酶和小G蛋白等多种转导分子一起，沿着在质膜上聚集形成膜微区（脂筏）。然而，GSL介导的生物学功能仍不清楚。乳糖神经酰胺（LacCer，CDw 17）在人吞噬细胞的质膜上高度表达，并介导几种免疫和炎症反应，包括吞噬作用、趋化性和超氧化物生成。LacCer与Src家族酪氨酸激酶林恩和异源三聚体G蛋白的Gαi亚基形成膜微区。极长脂肪酸C24：0和C24：1是中性粒细胞质膜中LacCer的主要神经酰胺组分，并与林恩和Gαi的脂肪酸直接相关。这些观察结果表明，神经酰胺的非常长的脂肪酸链是GSL介导的由外向内信号传导的关键。鞘氨醇是神经酰胺的另一种成分，神经酰胺酶水解神经酰胺产生鞘氨醇和脂肪酸。鞘氨醇被鞘氨醇激酶磷酸化为鞘氨醇-1-磷酸，其参与多种细胞功能，包括各种类型细胞的生长、分化、存活、趋化性、血管生成和胚胎发生。本文综述了GSL及其代谢产物神经酰胺在人体免疫和炎症反应中的作用。
Glycosphingolipids (GSLs) are composed of hydrophobic ceramide and hydrophilic sugar chains. GSLs cluster to form membrane microdomains (lipid rafts) on plasma membranes, along with several kinds of transducer molecules, including Src family kinases and small G proteins. However, GSL-mediated biological functions remain unclear. Lactosylceramide (LacCer, CDw17) is highly expressed on the plasma membranes of human phagocytes and mediates several immunological and inflammatory reactions, including phagocytosis, chemotaxis, and superoxide generation. LacCer forms membrane microdomains with the Src family tyrosine kinase Lyn and the Gαi subunit of heterotrimeric G proteins. The very long fatty acids C24:0 and C24:1 are the main ceramide components of LacCer in neutrophil plasma membranes and are directly connected with the fatty acids of Lyn and Gαi. These observations suggest that the very long fatty acid chains of ceramide are critical for GSL-mediated outside-in signaling. Sphingosine is another component of ceramide, with the hydrolysis of ceramide by ceramidase producing sphingosine and fatty acids. Sphingosine is phosphorylated by sphingosine kinase to sphingosine-1-phosphate, which is involved in a wide range of cellular functions, including growth, differentiation, survival, chemotaxis, angiogenesis, and embryogenesis, in various types of cells. This review describes the role of ceramide moiety of GSLs and its metabolites in immunological and inflammatory reactions in human.