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探索葡聚糖颗粒在人原代细胞中的免疫调节特性。

Exploring the immunomodulatory properties of glucan particles in human primary cells.

机构信息

CNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Portugal.

CNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Portugal.

出版信息

Int J Pharm. 2024 Apr 25;655:123996. doi: 10.1016/j.ijpharm.2024.123996. Epub 2024 Mar 14.

Abstract

The immunomodulatory properties of β-glucans have sparked interest among various medical fields. As vaccine adjuvants, glucan particles offer additional advantages as antigen delivery systems. This study reported the immunomodulatory properties of glucan particles with different size and chemical composition. The effect of glucan microparticles (GPs) and glucan nanoparticles (Glu 130 and 355 NPs) was evaluated on human immune cells. While GPs and Glu 355 NPs demonstrated substantial interaction with Dectin-1 receptor on monocytes, Glu 130 NPs exhibited reduced activation of this receptor. This observation was substantiated by blocking Dectin-1, resulting in inhibition of reactive oxygen species production induced by GPs and Glu 355 NPs. Notably, monocyte-derived dendritic cells (moDCs) stimulated by Glu 355 NPs exhibited phenotypic and functional maturation, essential for antigen cross-presentation. The immunomodulatory efficacy was investigated using an autologous mixed lymphocyte reaction (AMLR), resulting in considerable rates of lymphocyte proliferation and an intriguing profile of cytokine and chemokine release. Our findings highlight the importance of meticulously characterizing the size and chemical composition of β-glucan particles to draw accurate conclusions regarding their immunomodulatory activity. This in vitro model mimics the human cellular immune response, and the results obtained endorse the use of β-glucan-based delivery systems as future vaccine adjuvants.

摘要

β-葡聚糖的免疫调节特性引起了各个医学领域的兴趣。作为疫苗佐剂,葡聚糖颗粒作为抗原递送系统具有额外的优势。本研究报道了具有不同大小和化学组成的葡聚糖颗粒的免疫调节特性。评估了葡聚糖微颗粒(GPs)和葡聚糖纳米颗粒(Glu 130 和 355 NPs)对人免疫细胞的影响。虽然 GPs 和 Glu 355 NPs 与单核细胞上的 Dectin-1 受体有显著相互作用,但 Glu 130 NPs 对该受体的激活作用降低。通过阻断 Dectin-1,抑制 GPs 和 Glu 355 NPs 诱导的活性氧物质产生,证实了这一观察结果。值得注意的是,由 Glu 355 NPs 刺激的单核细胞来源的树突状细胞(moDCs)表现出表型和功能成熟,这对于抗原交叉呈递至关重要。通过自体混合淋巴细胞反应(AMLR)研究了免疫调节功效,导致淋巴细胞增殖率相当高,并释放出有趣的细胞因子和趋化因子谱。我们的研究结果强调了仔细表征β-葡聚糖颗粒的大小和化学组成的重要性,以便对其免疫调节活性得出准确的结论。该体外模型模拟了人类细胞免疫反应,并且获得的结果支持使用基于β-葡聚糖的递送系统作为未来的疫苗佐剂。

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