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The size of micro-crystalline tyrosine (MCT?) influences its recognition and uptake by THP-1 macrophages in vitro

机译:微晶酪氨酸(MCT?)的大小影响THP-1巨噬细胞在体外对其的识别和摄取

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The physicochemical hallmarks of particulate immunopotentiators play a pivotal role with regards to their adjuvanticity in vivo . These properties have not been fully characterised in the case of MCT?, an amino acid-based adjuvant used as an alternative to aluminium salts in subcutaneous allergy immunotherapy (SCIT). This study presents a full characterisation of MCT? and in a preliminary capacity reveals how parameters, specifically particle size, might influence the recognition of MCT? by antigen presenting cells (APCs) in vitro . Light microscopic analysis demonstrated that MCT? was composed of highly crystalline needles, the majority of which exceeded 10 μm in length under physiological conditions (median size – 20.8 μm). While the substantial length of crystals presented a significant barrier to cellular recognition and uptake, isolated incidences of perpendicular recognition were observed owing to the smaller comparative width of crystallites (median size – 2.8 μm). This appeared to allow a small proportion of material to be ingested both fully and partially by THP-1 macrophages, although further studies are required to unequivocally confirm this observation. Preferential recognition of needle tips also favoured the direct presentation of antigen to immune cells as proteinaceous adsorption appeared to be isolated to these regions. Furthermore, the data herein provide valuable insights into the mechanisms surrounding how this adjuvant potentiates an immunological response following administration.
机译:颗粒免疫增强剂的理化标志在体内佐剂方面起着关键作用。在MCT 3的情况下,这些特性尚未得到充分表征,MCT 3是一种氨基酸基佐剂,可替代皮下变态免疫疗法(SCIT)中的铝盐。这项研究提出了MCT的完整特征?并初步揭示了参数(尤其是粒径)如何影响MCT的识别?通过抗原呈递细胞(APC)在体外进行。光学显微镜分析表明MCT?由高度结晶的针组成,在生理条件下(中位大小为20.8μm),大多数针的长度超过10μm。尽管相当长的晶体对细胞的识别和吸收构成了显着障碍,但由于微晶的比较宽度较小(中值尺寸为2.8μm),因此观察到了垂直识别的孤立现象。这似乎允许一小部分物质被THP-1巨噬细胞完全或部分摄入,尽管还需要进一步的研究来明确证实这一观察结果。优先识别针尖也有利于将抗原直接呈递给免疫细胞,因为蛋白质吸附似乎被隔离到这些区域。此外,本文的数据提供了有关该佐剂在给药后如何增强免疫应答的机制的宝贵见解。

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