Induction of human neutrophil chemotaxis by Candida albicans-derived β-1,6-long glycoside side-chain-branched β-glucan
Induction of human neutrophil chemotaxis by Candida albicans-derived β-1,6-long glycoside side-chain-branched β-glucan
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DOI：
10.1189/jlb.0106069
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发表时间：
2006-07-01
影响因子：
5.5
通讯作者：
Ogawa, Hideoki
中科院分区：
文献类型：
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作者：
Sato, Tadashi;Iwabuchi, Kazuhisa;Ogawa, Hideoki
多糖β-1，3-D-葡聚糖（β-葡聚糖）是各种真菌细胞壁的成分，具有免疫调节活性。据报道，β-葡聚糖在病原性真菌诱导的肺部炎症过程中可增强神经肽的积累。因此，我们研究了β-葡聚糖本身是否对人类中性粒细胞具有趋化活性。在几种β-葡聚糖中，从白色念珠菌中分离的β-1，6-长葡糖基侧链分支β-葡聚糖[念珠菌可溶性β-D-葡聚糖（CSBG）]在Boyden室系统中剂量依赖性地诱导神经元迁移。相比之下，1，6-单葡糖基支链β-葡聚糖，如来自非病原性真菌的来自皱序雀麦的β-葡聚糖（SCG）和灰树花多糖（GRN），几乎不诱导中性粒细胞迁移。此外，含有中性鞘糖脂乳糖神经酰胺（LacCer; Gal β 1- 4Glc-神经酰胺）但不含NeuAc α 2-3Gal β 1 - 4Glc β 1- 1 '-Ccr神经节苷脂的脂质体可完全抑制CSBG诱导的中性粒细胞迁移。此外，结合实验表明，CSBG与具有末端半乳糖残基的鞘糖脂（如LacCer）结合;然而，SCG和GRN（1，6-糖基支链β-葡聚糖）不与LacCer结合。重要的是，Src激酶抑制剂蛋白磷酸酶1、磷脂酰肌醇-3激酶（PI-3 K）抑制剂渥曼青霉素和G α（i/o）抑制剂百日咳毒素抑制了脑膜炎向CSBG的迁移。综上所述，我们的结果表明，β-1，6-长葡糖基侧链分支β-葡聚糖CSBG结合LacCer，并通过激活Src家族激酶/PI-3 K/异源三聚体G蛋白信号转导途径诱导神经元迁移。
Polysaccharide beta-1,3-D-glucans (beta-glucans) are components of the cell wall of various fungi and show immunomodulatory activities. beta-Glucans have been reported to enhance nentrophil accumulation during pathogenic fungi-induced lung inflammation. Therefore, we examined whether beta-glucans themselves possess chemotactic activities for human neutrophils. Among several kinds of beta-glucans, beta-1,6-long glucosyl side-chain-branched P-glucan, isolated from Candida albicans [Candida soluble beta-D-glucan (CSBG)], dose-dependently induced nentrophil migration in a Boyden chamber system. In contrast, 1,6-monoglucosyl-branched beta-glucans, such as Sparassis crispa-derived beta-glucan (SCG) and grifolan (GRN), which were derived from nonpathogenic fungi, hardly induced neutrophil migration. Moreover, CSBG-induced neutrophil migration was inhibited completely by liposomes containing neutral glycosphingolipid lactosylceramide (LacCer; Gal beta 1-4Glc-ceramide) but not NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'-Ccr ganglioside. Furthermore, binding experiments demonstrated that CSBG bound to glycosphingolipids (such as LacCer) with a terminal galactose residue; however, SCG and GRN (1,6-nionoglucosylbranched beta-glucans) did not bind to LacCer. It is important that a Src kinase inhibitor protein phosphatase 1, a phosphatidylinositol-3 kinase (PI-3K) inhibitor wortmannin, and a G alpha(i/o) inhibitor pertussis toxin inhibited nentrophil migration toward CSBG. Taken together, our results suggest that beta-1,6-long glucosyl side-chain-branched beta-glucan CSBG binds to LacCer and induces nentrophil migration through the activation of Src family kinase/PI-3K/heterotrimeric G-protein signal transduction pathways.