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铝佐剂与体外 THP-1 巨噬细胞的相互作用:对细胞存活和全身转移的影响。

The interaction of aluminium-based adjuvants with THP-1 macrophages in vitro: Implications for cellular survival and systemic translocation.

机构信息

The Birchall Centre, Lennard-Jones Laboratories, Keele University, Keele, Staffordshire ST5 5BG, UK.

The Birchall Centre, Lennard-Jones Laboratories, Keele University, Keele, Staffordshire ST5 5BG, UK.

出版信息

J Inorg Biochem. 2020 Feb;203:110915. doi: 10.1016/j.jinorgbio.2019.110915. Epub 2019 Nov 12.

Abstract

Within clinical vaccinations, recombinant antigens are routinely entrapped inside or adsorbed onto the surface of aluminium salts in order to increase their immunological potency in vivo. The efficacy of these immunisations is highly dependent upon the recognition and uptake of these complexes by professional phagocytes and their subsequent delivery to the draining lymph nodes for further immunological processing. While monocytes have been shown to internalise aluminium adjuvants and their adsorbates, the role of macrophages in this respect has not been fully established. Furthermore, this study explored the interaction of THP-1 macrophages with aluminium-based adjuvants (ABAs) and how this relationship influenced the survival of such cells in vitro. THP-1 macrophages were exposed to low concentrations of ABAs (1.7 μg/mL Al) for a maximum of seven days. ABA uptake was determined using lumogallion staining and cell viability by both DAPI (4',6-diamidino-2-phenylindole) staining and LDH (lactate dehydrogenase) assay. Evidence of ABA particle loading was identified within cells at early junctures following treatment and appeared to be quite prolific (>90% cells positive for Al signal after 24 h). Total sample viability (% LDH release) in treated samples was predominantly similar to untreated cells and low levels of cellular death were consistently observed in populations positive for Al uptake. It can thus be concluded that aluminium salts can persist for some time within the intracellular environment of these cells without adversely affecting their viability. These results imply that macrophages may play a role in the systemic translocation of ABAs once administered in the form of an inoculation.

摘要

在临床疫苗接种中,重组抗原通常被包裹在铝盐内部或吸附在其表面,以提高其在体内的免疫效力。这些免疫接种的效果高度依赖于专业吞噬细胞对这些复合物的识别和摄取,以及随后将其递送到引流淋巴结进行进一步的免疫处理。虽然已经证明单核细胞可以内化铝佐剂及其吸附物,但巨噬细胞在这方面的作用尚未完全确定。此外,本研究探讨了 THP-1 巨噬细胞与铝基佐剂(ABAs)的相互作用,以及这种关系如何影响这些细胞在体外的存活。THP-1 巨噬细胞暴露于低浓度的 ABAs(1.7μg/mL Al)最多 7 天。使用鲁米诺镓染色测定 ABA 摄取,并用 DAPI(4',6-二脒基-2-苯基吲哚)染色和 LDH(乳酸脱氢酶)测定法测定细胞活力。在处理后早期,细胞内就已经发现了 ABA 颗粒负载的证据,而且似乎非常丰富(处理 24 小时后,超过 90%的细胞呈阳性)。处理样品中的总样品活力(%LDH 释放)与未处理细胞基本相似,并且在摄取 Al 的细胞群体中始终观察到低水平的细胞死亡。因此可以得出结论,铝盐可以在这些细胞的细胞内环境中存在一段时间而不会对其活力产生不利影响。这些结果表明,一旦以接种的形式给予,巨噬细胞可能在 ABAs 的全身转运中发挥作用。

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