Shear Stress Induces a Time-Dependent Inflammatory Response in Human Monocyte-Derived Macrophages

IF 3 2区 医学 Q3 ENGINEERING, BIOMEDICAL Annals of Biomedical Engineering Pub Date : 2024-09-17 DOI:10.1007/s10439-024-03546-5
Elysa Jui, Griffin Kingsley, Hong Kim T. Phan, Kavya L. Singampalli, Ravi K. Birla, Jennifer P. Connell, Sundeep G. Keswani, K. Jane Grande-Allen
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Abstract

Macrophages are innate immune cells that are known for their extreme plasticity, enabling diverse phenotypes that lie on a continuum. In a simplified model, they switch between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes depending on surrounding microenvironmental cues, which have been implicated in disease outcomes. Although considerable research has been focused on macrophage response to biochemical cues and mechanical signals, there is a scarcity of knowledge surrounding their behavior in response to shear stress. In this study, we applied varying magnitudes of shear stress on human monocyte-derived macrophages (MDMs) using a cone-and-plate viscometer and evaluated changes in morphology, gene expression, protein expression, and cytokine secretion over time. MDMs exposed to shear stress exhibited a rounder morphology compared to statically-cultured controls. RT-qPCR results showed significant upregulation of TNF-α, and analysis of cytokine release revealed increased secretion of IL-8, IL-18, fractalkine, and other chemokines. The upregulation of pro-inflammatory factors was evident with both increasing magnitudes of shear and time. Taken together, these results indicate that prolonged shear exposure induced a pro-inflammatory phenotype in human MDMs. These findings have implications for medical technology development, such as in situ vascular graft design wherein macrophages are exposed to shear and have been shown to affect graft resorption, and in delineating disease pathophysiology, for example to further illuminate the role of macrophages in atherosclerosis where shear is directly related to disease outcome.

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剪切应力诱导人类单核细胞衍生巨噬细胞产生时间依赖性炎症反应
巨噬细胞是一种先天性免疫细胞,以其极强的可塑性而闻名,能产生连续的多种表型。在一个简化模型中,巨噬细胞会根据周围微环境线索在促炎(M1)和抗炎(M2)表型之间切换,这与疾病结果有关。虽然大量研究都集中在巨噬细胞对生化线索和机械信号的反应上,但有关它们对剪切应力的反应行为的知识还很匮乏。在这项研究中,我们使用锥板粘度计对人类单核细胞衍生巨噬细胞(MDMs)施加了不同程度的剪切应力,并评估了其形态、基因表达、蛋白质表达和细胞因子分泌随时间的变化。与静态培养的对照组相比,暴露在剪切应力下的 MDM 形态更圆。RT-qPCR 结果显示 TNF-α 明显上调,细胞因子释放分析显示 IL-8、IL-18、fractalkine 和其他趋化因子分泌增加。随着剪切力和时间的增加,促炎因子的上调都很明显。综上所述,这些结果表明,长时间的剪切暴露会诱导人类 MDMs 产生促炎表型。这些发现对医疗技术的开发具有重要意义,例如在原位血管移植设计中,巨噬细胞暴露在剪切力下,已被证明会影响移植体的吸收;对疾病病理生理学的研究也具有重要意义,例如进一步阐明巨噬细胞在动脉粥样硬化中的作用,因为剪切力与疾病结果直接相关。
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来源期刊
Annals of Biomedical Engineering
Annals of Biomedical Engineering 工程技术-工程:生物医学
CiteScore
7.50
自引率
15.80%
发文量
212
审稿时长
3 months
期刊介绍: Annals of Biomedical Engineering is an official journal of the Biomedical Engineering Society, publishing original articles in the major fields of bioengineering and biomedical engineering. The Annals is an interdisciplinary and international journal with the aim to highlight integrated approaches to the solutions of biological and biomedical problems.
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