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表面化学诱导的免疫球蛋白G展开及免疫反应调节

Surface Chemistry Induced IgG Unfolding and Modulation of Immune Responses.

作者信息

Alemie Markos Negash, Bright Richard, Nguyen Ngoc Huu, Truong Vi Khanh, Palms Dennis, Hayball John D, Vasilev Krasimir

机构信息

Experimental Therapeutics Laboratory, UniSA Clinical and Health Sciences. University of South Australia, City East Campus, Adelaide 5000, Australia.

College of Medicine and Public Health, Flinders University, Bedford Park, South Australia 5042, Australia.

出版信息

ACS Appl Mater Interfaces. 2024 Sep 25;16(38):50507-50523. doi: 10.1021/acsami.4c12883. Epub 2024 Sep 12.

DOI:10.1021/acsami.4c12883
PMID:39263871
Abstract

Immunoglobulin G (IgG) comprises a significant portion of the protein corona that forms on biomaterial surfaces and holds a pivotal role in modulating host immune responses. To shed light on the important relationship between biomaterial surface functionality, IgG adsorption, and innate immune responses, we prepared, using plasma deposition, four surface coatings with specific chemistries, wettability, and charge. We found that nitrogen-containing coatings such as these deposited from allylamine (AM) and 2-methyl-2-oxazoline (POX) cause the greatest IgG unfolding, while hydrophilic acrylic acid (AC) surfaces allowed for the retention of the protein structure. Structural changes in IgG significantly modulated macrophage attachment, migration, polarization, and the expression of pro- and anti-inflammatory cytokines. Unfolded IgG on the POX and AM surfaces enhanced macrophage attachment, migration, extracellular trap release, and pro-inflammatory factors production such as IL-6 and TNF-α. Retention of IgG structure on the AC surface downregulated inflammatory responses. The findings of this study demonstrate that the retention of protein structure is an essential factor that must be taken into consideration when designing biomaterial surfaces. Our study indicates that using hydrophilic surface coatings could be a promising strategy for designing immune-modulatory biomaterials for clinical applications.

摘要

免疫球蛋白G(IgG)是在生物材料表面形成的蛋白质冠层的重要组成部分,在调节宿主免疫反应中起关键作用。为了阐明生物材料表面功能、IgG吸附和固有免疫反应之间的重要关系,我们利用等离子体沉积制备了四种具有特定化学性质、润湿性和电荷的表面涂层。我们发现,由烯丙胺(AM)和2-甲基-2-恶唑啉(POX)沉积的此类含氮涂层会导致IgG最大程度的展开,而亲水性丙烯酸(AC)表面则能使蛋白质结构得以保留。IgG的结构变化显著调节了巨噬细胞的附着、迁移、极化以及促炎和抗炎细胞因子的表达。POX和AM表面上展开的IgG增强了巨噬细胞的附着、迁移、细胞外陷阱释放以及促炎因子如IL-6和TNF-α的产生。AC表面上IgG结构的保留下调了炎症反应。本研究结果表明,蛋白质结构的保留是设计生物材料表面时必须考虑的一个重要因素。我们的研究表明,使用亲水性表面涂层可能是设计用于临床应用的免疫调节生物材料的一种有前景的策略。

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