人类中性粒细胞重新招募的高透量和在空气血液屏障阵列中的功能性反应
bioRxiv : the preprint server for biology
|May 27, 2024
概括
在空气-血液屏障阵列 (L-ABBA-96) 试验中,一种新的96孔白细胞招募使得肺中性恋的高通量研究成为可能. 这种模型推进了对ARDS和囊性纤维化等肺部疾病的药物测试.
科学领域:
- 肺部医学 肺部医学
- 免疫学 免疫学 免疫学
- 生物医学工程 生物医学工程
背景情况:
- 肺部疾病是由失调的中性粒细胞招募驱动的,但目前的查方法不足以研究肺中性粒细胞.
- 高通量查系统往往忽略了中性恋病理生理学的关键方面,例如血液到肺部的招募和空气血液屏障的影响.
研究的目的:
- 开发一种高通量试验,以模拟肺部中性粒细胞的活体样式招募.
- 为了同时实现生理复杂性和肺中性恋的有效查.
主要方法:
- 在空气-血液屏障阵列 (L-ABBA-96) 试验中开发了96孔白细胞招募方法.
- 模拟的急性呼吸困扰综合征 (ARDS) 使用介素-8 (IL-8) 诱导中性粒细胞的招募.
- 测试了巴里西提尼布的疗效,并分析了患者衍生的囊性纤维化吐对中性粒细胞的超级效应.
主要成果:
- L-ABBA-96试验显示,巴里西提尼布对中性粒细胞招募的剂量依赖性降低.
- 囊性纤维化唾液超诱导疾病模仿性中性粒细胞的招募和激活,上调内皮电子选择蛋白.
- 与现有的24孔和微流体测定相比,L-ABBA-96测定提供了显著更高的吞吐量和中性粒细胞招募率.
结论:
- L-ABBA-96试验为研究肺部白细胞功能的研究提供了一个强大的平台.
- 这种测定有助于推进临床前药物测试,个性化医学和肺部疾病的病理生理学研究.
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