Ignes-Romeu Aitana, Weppner Hannah K, Kaur Tanisha, Singh Maya, Hind Laurel E
Department of Chemical and Biological Engineering, University of Colorado - Boulder, Boulder, CO 80303 USA.
Present Address: Department of Bioengineering, University of Washington, Seattle, WA 98195 USA.
Cell Mol Bioeng. 2024 Jul 20;17(4):279-293. doi: 10.1007/s12195-024-00813-2. eCollection 2024 Aug.
Dysregulated neutrophil function plays a significant role in the pathology of infections, cancer, cardiovascular diseases, and autoimmune disorders. Neutrophil activity is influenced by various cell populations, including macrophages, which are crucial regulators. However, the exact role of human macrophages in controlling neutrophil function remains unclear due to a scarcity of studies utilizing human cells in physiologically relevant models.
We adapted our "Infection-on-a-Chip" microfluidic device to incorporate macrophages within the collagen extracellular matrix, allowing for the study of interactions between human neutrophils and macrophages in a context that mimics in vivo conditions. The integration of THP-1 macrophages was optimized and their effect on the endothelial lumen was characterized, focusing on permeability and structural integrity. The device was then employed to examine the influence of macrophages on neutrophil response to infection with the bacterial pathogen .
Integration of THP-1 macrophages into the microfluidic device was successfully optimized, showing no increase in endothelial permeability or structural damage. The presence of macrophages was found to significantly reduce neutrophil transendothelial migration in response to infection.
Our findings highlight the regulatory role of macrophages in modulating neutrophil responses, suggesting potential therapeutic targets to control neutrophil function in various diseases. The modified microfluidic platform offers a valuable tool for mechanistic studies into macrophage-neutrophil interactions in disease contexts.
The online version contains supplementary material available at 10.1007/s12195-024-00813-2.
中性粒细胞功能失调在感染、癌症、心血管疾病和自身免疫性疾病的病理过程中起着重要作用。中性粒细胞的活性受多种细胞群体影响，包括作为关键调节因子的巨噬细胞。然而，由于在生理相关模型中利用人类细胞的研究较少，人类巨噬细胞在控制中性粒细胞功能方面的确切作用仍不清楚。
我们对“芯片上的感染”微流控装置进行了改进，将巨噬细胞整合到胶原蛋白细胞外基质中，以便在模拟体内条件的环境中研究人类中性粒细胞与巨噬细胞之间的相互作用。优化了THP-1巨噬细胞的整合，并对其对内皮管腔的影响进行了表征，重点关注通透性和结构完整性。然后使用该装置研究巨噬细胞对中性粒细胞对细菌病原体感染反应的影响。
成功优化了THP-1巨噬细胞在微流控装置中的整合，未显示内皮通透性增加或结构损伤。发现巨噬细胞的存在显著减少了中性粒细胞对感染的跨内皮迁移。
我们的研究结果突出了巨噬细胞在调节中性粒细胞反应中的调节作用，提示了在各种疾病中控制中性粒细胞功能的潜在治疗靶点。改进后的微流控平台为在疾病背景下研究巨噬细胞-中性粒细胞相互作用的机制提供了有价值的工具。
在线版本包含可在10.1007/s12195-024-00813-2获取的补充材料。
