Institute of Applied Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, P.R. China.
Department of Physics and Astronomy, University of Manitoba, Winnipeg, MB, Canada.
Sci Rep. 2017 Jun 8;7(1):3100. doi: 10.1038/s41598-017-03210-0.
Neutrophil trafficking in tissues critically regulates the body's immune response. Neutrophil migration can either play a protective role in host defense or cause health problems. Fibroblast growth factor 23 (FGF23) is a known biomarker for chronic kidney disease (CKD) and was recently shown to impair neutrophil arrest on endothelium and transendothelial migration. In the present study, we further examined the effect of FGF23 on human blood neutrophil chemotaxis using two new microfluidic devices. Our results showed that chemotaxis of FGF23 pre-treated neutrophils to a fMLP gradient, in the presence or absence of a uniform FGF23 background, is quantitatively lower compared to the control cells. This effect is accompanied with a stronger drifting of FGF23 pre-treated cells along the flow. However, without the FGF23 pre-treatment, the FGF23 background only reduces chemotaxis of transmigrated cells through the thin barrier channel to the fMLP gradient. The effect of FGF23 on neutrophil migration and the correlation between multiple cell migration parameters are further revealed by chemotactic entropy and principle component analysis. Collectively, these results revealed the effect of FGF23 on weakening neutrophil chemotaxis, which shed light on FGF23 mediated neutrophil migration with direct disease relevance such as CKD.
中性粒细胞在组织中的迁移对机体免疫反应起着至关重要的调控作用。中性粒细胞的迁移既可以在宿主防御中发挥保护作用，也可能导致健康问题。成纤维细胞生长因子 23（FGF23）是慢性肾脏病（CKD）的已知生物标志物，最近研究表明其可损害中性粒细胞在内皮细胞上的阻滞和跨内皮迁移。在本研究中，我们使用两种新的微流控设备进一步研究了 FGF23 对人血中性粒细胞趋化性的影响。结果显示，与对照细胞相比，预先用 FGF23 处理的中性粒细胞向 fMLP 梯度的趋化性在存在或不存在均匀 FGF23 背景的情况下呈定量降低。这种效应伴随着 FGF23 预处理细胞沿流动方向更强的漂移。然而，在没有 FGF23 预处理的情况下，FGF23 背景仅会降低穿过薄屏障通道向 fMLP 梯度迁移的细胞的趋化性。趋化性熵和主成分分析进一步揭示了 FGF23 对中性粒细胞迁移的影响及其与多个细胞迁移参数之间的相关性。总的来说，这些结果揭示了 FGF23 对中性粒细胞趋化性减弱的作用，这为 FGF23 介导的与直接疾病相关的中性粒细胞迁移（如 CKD）提供了新的认识。
