Department of Cardiology, Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany.
Department of Cardiology, Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany; Department of Cardiology, University of Giessen, Medical Clinic I, Giessen, Germany.
PLoS One. 2014 Jun 3;9(6):e98456. doi: 10.1371/journal.pone.0098456. eCollection 2014.
Mouse models of myocardial infarction (MI) are commonly used to explore the pathophysiological role of the monocytic response in myocardial injury and to develop translational strategies. However, no study thus far has examined the potential impact of inter-individual variability and sham surgical procedures on monocyte subset kinetics after experimental MI in mice. Our goal was to investigate determinants of systemic myeloid cell subset shifts in C57BL/6 mice following MI by developing a protocol for sequential extensive flow cytometry (FCM).
Following cross-sectional multiplex FCM analysis we provide for the first time a detailed description of absolute quantities, relative subset composition, and biological variability of circulating classical, intermediate, and non-classical monocyte subsets in C57BL/6 mice. By using intra-individual longitudinal measurements after MI induction, a time course of classical and non-classical monocytosis was recorded. This approach disclosed a significant reduction of monocyte subset dispersion across all investigated time points following MI. We found that in the current invasive model of chronic MI the global pattern of systemic monocyte kinetics is mainly determined by a nonspecific inflammatory response to sham surgery and not by the extent of myocardial injury.
Application of sequential multiplexed FCM may help to reduce the impact of biological variability in C57BL/6 mice. Furthermore, the confounding influence of sham surgical procedures should always be considered when measuring monocyte subset kinetics in a murine model of MI.
心肌梗死（MI）的小鼠模型常用于探索单核细胞反应在心肌损伤中的病理生理作用，并开发转化策略。然而，迄今为止，尚无研究探讨个体间变异性和假手术程序对实验性 MI 后小鼠单核细胞亚群动力学的潜在影响。我们的目标是通过开发一种用于连续广泛流式细胞术（FCM）的方案，研究 MI 后 C57BL/6 小鼠系统髓样细胞亚群转移的决定因素。
在进行横断面多重 FCM 分析后，我们首次详细描述了 C57BL/6 小鼠循环中经典、中间和非经典单核细胞亚群的绝对数量、相对亚群组成和生物学变异性。通过在 MI 诱导后进行个体内纵向测量，记录了经典和非经典单核细胞增多的时间过程。这种方法揭示了 MI 后所有研究时间点单核细胞亚群分散的显著减少。我们发现，在当前慢性 MI 的侵入性模型中，系统性单核细胞动力学的整体模式主要由假手术的非特异性炎症反应决定，而不是由心肌损伤的程度决定。
应用连续多重 FCM 可能有助于减少 C57BL/6 小鼠中生物学变异性的影响。此外，在测量 MI 小鼠模型中的单核细胞亚群动力学时，应始终考虑假手术程序的混杂影响。
