An open microfluidic coculture model of fibroblasts and eosinophils to investigate mechanisms of airway inflammation.
An open microfluidic coculture model of fibroblasts and eosinophils to investigate mechanisms of airway inflammation.
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DOI：
10.3389/fbioe.2022.993872
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发表时间：
2022
影响因子：
5.7
通讯作者：
Theberge, Ashleigh B. B.
中科院分区：
文献类型：
--
作者：
Zeng, Yuting;Su, Xiaojing;Takezawa, Meg G. G.;Fichtinger, Paul S. S.;Lee, Ulri N. N.;Pippin, Jeffery W. W.;Shankland, Stuart J. J.;Lim, Fang Yun;Denlinger, Loren C. C.;Jarjour, Nizar N. N.;Mathur, Sameer K. K.;Sandbo, Nathan;Berthier, Erwin;Esnault, Stephane;Bernau, Ksenija;Theberge, Ashleigh B. B.
成纤维细胞和免疫细胞之间的相互作用在组织炎症中起重要作用。以前的研究发现，白细胞介素-3（IL-3）激活的嗜酸性粒细胞对聚集的免疫球蛋白G（IgG）具有抑制作用，并释放激活肺中成纤维细胞的介质。然而，这些研究是用嗜酸性粒细胞条件培养基进行的，其仅能够研究从嗜酸性粒细胞到成纤维细胞的单向信号传导。在这里，我们展示了一个共培养模型的原代正常人肺成纤维细胞（HLF）和人血嗜酸性粒细胞过敏和哮喘患者使用开放的微流体共培养装置。在我们的设备中，这两种类型的细胞可以通过共享介质中的双向可溶性因子信号传导进行通信，同时被半壁物理隔离。最初，我们通过嗜酸性粒细胞源性神经毒素（EDN）的释放来评估嗜酸性粒细胞脱粒的水平。接下来，我们分别使用逆转录定量聚合酶链反应（RT-qPCR）和多重免疫测定分析了炎症相关基因和可溶性因子。我们的研究结果表明，诱导一个促炎性成纤维细胞表型的HLF后，与脱粒嗜酸性粒细胞共培养，验证了我们以前的研究结果。此外，我们提出了一个新的结果，表明激活的HLF对嗜酸性粒细胞的潜在影响。这种开放的微流控共培养平台提供了独特的机会来研究两种细胞类型之间的细胞间信号传导及其在气道炎症和重塑中的作用。
Interactions between fibroblasts and immune cells play an important role in tissue inflammation. Previous studies have found that eosinophils activated with interleukin-3 (IL-3) degranulate on aggregated immunoglobulin G (IgG) and release mediators that activate fibroblasts in the lung. However, these studies were done with eosinophil-conditioned media that have the capacity to investigate only one-way signaling from eosinophils to fibroblasts. Here, we demonstrate a coculture model of primary normal human lung fibroblasts (HLFs) and human blood eosinophils from patients with allergy and asthma using an open microfluidic coculture device. In our device, the two types of cells can communicate via two-way soluble factor signaling in the shared media while being physically separated by a half wall. Initially, we assessed the level of eosinophil degranulation by their release of eosinophil-derived neurotoxin (EDN). Next, we analyzed the inflammation-associated genes and soluble factors using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and multiplex immunoassays, respectively. Our results suggest an induction of a proinflammatory fibroblast phenotype of HLFs following the coculture with degranulating eosinophils, validating our previous findings. Additionally, we present a new result that indicate potential impacts of activated HLFs back on eosinophils. This open microfluidic coculture platform provides unique opportunities to investigate the intercellular signaling between the two cell types and their roles in airway inflammation and remodeling.
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DOI：
10.4049/jimmunol.1500871
发表时间：
2015-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Esnault S;Kelly EA;Shen ZJ;Johansson MW;Malter JS;Jarjour NN
通讯作者：
Jarjour NN
DOI：
10.1073/pnas.1302566110
发表时间：
2013-06-18
影响因子：
11.1
作者：
Casavant, Benjamin P.;Berthier, Erwin;Beebe, David J.
通讯作者：
Beebe, David J.
影响因子：
14.2
作者：
Bernau, Ksenija;Leet, Jonathan P.;Sandbo, Nathan
通讯作者：
Sandbo, Nathan
影响因子：
6
作者：
Shen ZJ;Hu J;O'Neal MA;Malter JS
通讯作者：
Malter JS
影响因子：
5.8
作者：
Esnault S;Bernau K;Torr EE;Bochkov YA;Jarjour NN;Sandbo N
通讯作者：
Sandbo N