将功能性人体皮肤外植体作为评估肥大细胞活化和抑制的工具

IF 3.3 Q2 ALLERGY
Clarence Rachel Villanueva, Keane Barksdale, Tinuola Owolabi, Donavan Bridges, Kristin Chichester, Sarbjit Saini, Eric T. Oliver
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引用次数: 0

摘要

肥大细胞通过各种不同的受体激活,释放预先形成的颗粒和重新合成的介质。然而,人们对肥大细胞的生理和功能并不完全了解。对人体肥大细胞活化的传统研究利用的是组织来源的肥大细胞培养物,包括 CD34+ 祖细胞或特征明确的市售细胞系。这些方法的一个局限性是肥大细胞不再处于自然状态。因此,它们对人类皮肤疾病的适用性可能有限。人类皮肤外植体模型已被用于研究细胞介质、药物和刺激物对皮肤的短期影响,同时避免了使用未经批准的药物进行体内刺激研究的伦理问题。然而,很少有研究利用完整的人体组织来研究肥大细胞脱颗粒。本 "方法 "论文介绍了开发和应用完整皮肤外植体模型来研究人体肥大细胞活化的情况。在本手稿中,我们分享了建立体外人体皮肤外植体的方案,并描述了刺激实验的结果以及将创伤诱导的组胺释放降至最低的技术。皮肤外植体是使用整形和重建手术中的去标识、全厚、非病变皮肤标本制作的。结果具有可重复性,并证明了 FcɛRI-和 MRGPRX2 诱导的介质释放,而 BTK 抑制剂和 QWF 可分别抑制介质释放。因此,这种外植体模型为评估人类皮肤肥大细胞的活化和抑制提供了一种快速、简便的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Functional human skin explants as tools for assessing mast cell activation and inhibition
Mast cells are activated through a variety of different receptors to release preformed granules and mediators synthesized de novo. However, the physiology and function of mast cells are not fully understood. Traditional studies of mast cell activation in humans have utilized cultures of tissue-derived mast cells including CD34+ progenitor cells or well-characterized commercially available cell lines. One limitation of these methods is that mast cells are no longer in a natural state. Therefore, their applicability to human skin disorders may be limited. Human skin explant models have been utilized to investigate the short-term effects of cell mediators, drugs, and irritants on skin while avoiding the ethical concerns surrounding in vivo stimulation studies with non-approved agents. Nonetheless, few studies have utilized intact human tissue to study mast cell degranulation. This “Methods” paper describes the development and application of an intact skin explant model to study human mast cell activation. In this manuscript, we share our protocol for setting up ex vivo human skin explants and describe the results of stimulation experiments and techniques to minimize trauma-induced histamine release. Skin explants were generated using de-identified, full-thickness, non-diseased skin specimens from plastic and reconstructive surgeries. Results were reproducible and demonstrated FcɛRI- and MRGPRX2-induced mediator release which was inhibited with the use of a BTK inhibitor and QWF, respectively. Thus, this explant model provides a quick and accessible method of assessing human skin mast cell activation and inhibition.
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CiteScore
2.80
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