Laboratorio de Hematobiología, Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional, CDMX, Mexico.
Laboratorio de Hematobiología, Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional, CDMX, Mexico.
Exp Cell Res. 2021 May 15;402(2):112577. doi: 10.1016/j.yexcr.2021.112577. Epub 2021 Mar 31.
Cellular heterogeneity and diversity are recognized to contribute to the functions of neutrophils under homeostatic and pathological conditions. We previously suggested that the chronic inflammatory responses associated with hypertension (HTN) are related to the participation of different subpopulations of neutrophils. Two populations of neutrophils can be obtained by density gradient centrifugation: normal-density neutrophils (NDN) and low-density neutrophils (LDN). However, the lack of standardized functional protocols has limited phenotypic characterization and functional comparisons of LDN and NDN. Based on their capability to incorporate Na, maturity and activation stage, we characterized NDN and LDN in blood samples from ten patients with HTN and ten healthy individuals (HI) using flow cytometry. We compared the levels of reactive oxygen species (ROS), generation of neutrophil extracellular traps (NETs) and levels of apoptosis in NDN and LDN. In general, the NDN and LDN subpopulations from patients with HTN exhibited higher levels of sodium influx and ROS, and lower levels of apoptosis than the corresponding NDN and LDN subsets from HI. Transmission electron microscopy revealed NDN and LDN from patients with HTN exhibited alterations to mitochondrial morphology and fewer cytoplasmic granules than the corresponding HI subpopulations. Our results indicate both the NDN and LDN subpopulations enhance the effects of inflammation that contribute to the pathophysiology of HTN. Further detailed studies are required to characterize the events during ontogeny of the myeloid lineage that result in the diverse phenotypic characteristics of each subpopulation of LDN and NDN.
细胞异质性和多样性被认为有助于中性粒细胞在稳态和病理条件下发挥功能。我们之前曾提出,与高血压(HTN)相关的慢性炎症反应与不同亚群中性粒细胞的参与有关。通过密度梯度离心可以获得两种中性粒细胞群体:正常密度中性粒细胞(NDN)和低密度中性粒细胞(LDN)。然而,缺乏标准化的功能方案限制了 LDN 和 NDN 的表型特征和功能比较。基于它们摄取 Na 的能力、成熟度和激活阶段,我们使用流式细胞术对 10 名 HTN 患者和 10 名健康个体(HI)的血液样本中的 NDN 和 LDN 进行了特征描述。我们比较了 NDN 和 LDN 中的活性氧(ROS)水平、中性粒细胞胞外诱捕网(NETs)的产生和凋亡水平。一般来说,HTN 患者的 NDN 和 LDN 亚群表现出更高的钠离子内流和 ROS 水平,以及更低的凋亡水平,而 HI 对应的 NDN 和 LDN 亚群则较低。透射电子显微镜显示,HTN 患者的 NDN 和 LDN 表现出线粒体形态改变和细胞质颗粒较少,而 HI 对应的亚群则较少。我们的结果表明,NDN 和 LDN 亚群增强了炎症的作用,导致 HTN 的病理生理学。需要进一步详细的研究来描述骨髓谱系发生过程中的事件,这些事件导致每个 LDN 和 NDN 亚群表现出不同的表型特征。