Ekyalongo Roudy C, Nakayama Hitoshi, Kina Katsunari, Kaga Naoko, Iwabuchi Kazuhisa
Institute for Environmental and Gender-specific Medicine, Juntendo University Graduate School of Medicine, Japan.
Institute for Environmental and Gender-specific Medicine, Juntendo University Graduate School of Medicine, Japan; Laboratory of Biochemistry, Juntendo University School of Health Care and Nursing, Japan.
Biochim Biophys Acta. 2015 Jan;1851(1):90-7. doi: 10.1016/j.bbalip.2014.06.009. Epub 2014 Jun 23.
Populations of glycolipids change markedly during leukocyte differentiation, suggesting that these molecules are involved in biological functions. About 70% of the glycosphingolipids in human neutrophils are lactosylceramide, a molecule also expressed on monocytes and dendritic cells, but not on lymphocytes. In contrast, phosphatidylglucoside is mainly expressed on neutrophils. STED microscopic analysis showed that phosphatidylglucoside and lactosylceramide form different domains on plasma membranes of neutrophils, with phosphatidylglucoside preferentially expressed along the neutrophil differentiation pathway. Phosphatidylglucoside was found to mediate the differentiation of HL-60 cells into the neutrophilic lineage, and to be involved in FAS-dependent neutrophil apoptosis. In contrast, lactosylceramide was only expressed on mature neutrophils. Complexes of lactosylceramide and the Src family kinase Lyn form membrane microdomains. LacCer-enriched membrane microdomains mediate neutrophil innate immune responses; e.g. chemotaxis, phagocytosis, and superoxide generation. C24 fatty acid chains of LacCer are indispensable for the formation of LacCer-Lyn complexes and for LacCer-dependent functions. Moreover, Lyn-coupled LacCer-enriched microdomains serve as signal transduction platforms for αMβ2 integrin-mediated phagocytosis. This review describes the organization and potential functions of glycolipids in phagocytes, as well as the roles of both phosphatidylglucoside and lactosylceramide in neutrophils. This article is part of a Special Issue entitled Linking transcription to physiology in lipidomics.
糖脂群体在白细胞分化过程中发生显著变化，这表明这些分子参与了生物学功能。人类中性粒细胞中约70%的糖鞘脂是乳糖基神经酰胺，这种分子也在单核细胞和树突状细胞上表达，但不在淋巴细胞上表达。相比之下，磷脂酰葡萄糖主要在中性粒细胞上表达。受激发损耗（STED）显微镜分析表明，磷脂酰葡萄糖和乳糖基神经酰胺在中性粒细胞的质膜上形成不同的结构域，磷脂酰葡萄糖在中性粒细胞分化途径中优先表达。研究发现磷脂酰葡萄糖介导HL-60细胞向嗜中性粒细胞谱系分化，并参与FAS依赖的中性粒细胞凋亡。相比之下，乳糖基神经酰胺仅在成熟的中性粒细胞上表达。乳糖基神经酰胺与Src家族激酶Lyn形成膜微结构域。富含乳糖基神经酰胺的膜微结构域介导中性粒细胞的固有免疫反应，如趋化作用、吞噬作用和超氧化物生成。乳糖基神经酰胺的C24脂肪酸链对于乳糖基神经酰胺-Lyn复合物的形成和乳糖基神经酰胺依赖的功能不可或缺。此外，与Lyn偶联的富含乳糖基神经酰胺的微结构域作为αMβ2整合素介导的吞噬作用的信号转导平台。本综述描述了吞噬细胞中糖脂的组织和潜在功能，以及磷脂酰葡萄糖和乳糖基神经酰胺在中性粒细胞中的作用。本文是名为“脂质组学中连接转录与生理学”的特刊的一部分。
