Abstract
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.
Highlights
Cell migration significantly contributes to physiological and pathological processes such as host defense[1, 2], embryonic development[3], wound healing[4] and cancer metastasis[5]
Flowtaxis and the accuracy of chemotactic migration direction demonstrated the altered neutrophil migration by fibroblast growth factor 23 (FGF23). These findings suggested that a multi-parameter data mining approach may confirm the effect of FGF23 on neutrophil migration and reveal the relative importance and correlations of different cell migration parameters
Chemotaxis of FGF23 pre-treated neutrophils to fMLP was weakened in the presence or absence of a FGF23
Summary
Cell migration significantly contributes to physiological and pathological processes such as host defense[1, 2], embryonic development[3], wound healing[4] and cancer metastasis[5]. FGF23 was suggested to be a regulator for innate immunity[22] and human neutrophils express varying levels of FGFRs in their cytosol and on www.nature.com/scientificreports/ Their cytoplasmic membrane to interact with FGF2323. We developed an all-on-chip method for rapid neutrophil chemotaxis test by combining a microfluidic gradient generating device with the cell docking feature and an on-chip magnetic cell separation module directly from whole blood[28]. These previous developments built the background microfluidic technology for advanced cell migration and chemotaxis studies. In addition to the commonly used chemotaxis parameters such as chemotactic index and cell speed, we further applied the entropy analysis and the data mining approach to quantify the altered neutrophil migratory behaviors resulting from FGF23 exposure
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