Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Charlestown, MA, USA.
Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Charlestown, MA, USA; Harvard Medical School, Boston, MA, USA.
Cell Rep Methods. 2024 Sep 16;4(9):100846. doi: 10.1016/j.crmeth.2024.100846. Epub 2024 Sep 5.
Monocytes are critical to innate immunity, participating in chemotaxis during tissue injury, infection, and inflammatory conditions. However, the migration dynamics of human monocytes under different guidance cues are not well characterized. Here, we developed a microfluidic device to profile the migration characteristics of human monocytes under chemotactic and barotactic guidance cues while also assessing the effects of age and cytokine stimulation. Human monocytes preferentially migrated toward the CCL2 gradient through confined microchannels, regardless of donor age and migration pathway. Stimulation with interferon (IFN)-γ, but not granulocyte-macrophage colony-stimulating factor (GM-CSF), disrupted monocyte navigation through complex paths and decreased monocyte CCL2 chemotaxis, velocity, and CCR2 expression. Additionally, monocytes exhibited a bias toward low-hydraulic-resistance pathways in asymmetric environments, which remained consistent across donor ages, cytokine stimulation, and chemoattractants. This microfluidic system provides insights into the unique migratory behaviors of human monocytes and is a valuable tool for studying peripheral immune cell migration in health and disease.
单核细胞对于先天免疫至关重要，参与组织损伤、感染和炎症情况下的趋化作用。然而，不同趋化因子引导下的人单核细胞的迁移动态尚未得到很好的描述。在这里，我们开发了一种微流控装置，以分析趋化和趋压引导下的人单核细胞的迁移特征，同时评估年龄和细胞因子刺激的影响。人单核细胞优先通过受限的微通道向 CCL2 梯度迁移，而与供体年龄和迁移途径无关。用干扰素 (IFN)-γ 刺激，而不是用粒细胞-巨噬细胞集落刺激因子 (GM-CSF) 刺激，破坏了单核细胞通过复杂路径的导航，并降低了单核细胞 CCL2 的趋化性、速度和 CCR2 的表达。此外，单核细胞在不对称环境中偏向于低水力阻力途径，这种偏好在供体年龄、细胞因子刺激和趋化因子存在的情况下是一致的。该微流控系统提供了对人单核细胞独特迁移行为的深入了解，是研究健康和疾病状态下外周免疫细胞迁移的有价值工具。
