Heterogeneity of neutrophils in arterial hypertension

Cerecedo, Doris; Martínez‐Vieyra, Ivette; López-Villegas, Edgar Óliver; Hernández‐Cruz, Arturo; Loza-Huerta, Arlet

doi:10.1016/j.yexcr.2021.112577

Cited by 9 publications

(8 citation statements)

References 36 publications

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“…Thus, we believe that LDN are indeed present in low numbers in blood of healthy individuals. Our conclusion is similar to the conclusions reached in a study with asthmatic horses (37) and in two very recent reports on humans (54,72).…”

Section: Discussionsupporting

confidence: 93%

Low-Density Neutrophils in Healthy Individuals Display a Mature Primed Phenotype

2021

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Neutrophils are the most abundant leukocytes in human peripheral blood, comprising about 70% of all leukocytes. They are regarded as the first line of defense of the innate immune system, but neutrophils have also the ability of regulating the adaptive immune response. Recently, However, multiple phenotypes and functional states of neutrophils have been reported, particularly in inflammation, autoimmunity, and cancer. One possible subtype of neutrophils, the so-called low-density neutrophils (LDN) is found among mononuclear cells (MNC), monocytes and lymphocytes, after separating the leukocytes from blood by density gradient centrifugation. LDN increase in numbers during several pathological conditions. However, LDN present in healthy conditions have not been investigated further. Therefore, in order to confirm the presence of LDN in blood of healthy individuals and to explore some of their cellular functions, neutrophils and MNC were isolated by density gradient centrifugation. Purified neutrophils were further characterized by multicolor flow cytometry (FACS) and then, using the same FACS parameters cells in the MNC fraction were analyzed. Within the MNC, LDN were consistently found. These LDN had a normal mature neutrophil morphology and displayed a CD10+, CD11b+, CD14low, CD15high, CD16bhigh, CD62L+, CD66b+, and CXCR4+ phenotype. These LDN had an enhanced reactive oxygen species (ROS) production and increased phagocytic capacity and were able to produce neutrophil extracellular traps (NET) similarly to neutrophils. These data confirm the presence of a small number of LDN is blood of healthy individuals and suggest that these LDN represent mature cells with a primed phenotype.

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Section: Discussionsupporting

confidence: 93%

Low-Density Neutrophils in Healthy Individuals Display a Mature Primed Phenotype

2021

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“…Usually, granulocytes do not appear in the PBMCs but in the upper layer of the red blood cells (normal-density neutrophils, NDNs) when separating by Ficoll density gradient centrifugation method. Neutrophils in the PBMC layer, known as low-density neutrophils (LDNs), have been identified in systemic lupus erythematosus, rheumatoid arthritis, sepsis, asthma, natural pregnancy, tumors [ 22 ], COVID-19 [ 24 ], and arterial hypertension [ 25 ], but the function of LDNs in EH is not yet well defined.…”

Section: Resultsmentioning

confidence: 99%

“…Curiously, in our study, LDNs from hypertensive patients were reduced but with higher expressed antigens (except CD11b) compared to controls. Coincidentally, a recent study showed that patients with hypertension have a higher proportion of NDNs compared to healthy individuals [ 25 ]. Is there a correlation between LDNs and NDNs?…”

Section: Discussionmentioning

confidence: 99%

Mass Cytometry Reveals the Imbalanced Immune State in the Peripheral Blood of Patients with Essential Hypertension

Yang

Zhang

et al. 2023

Cardiovascular Therapeutics

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Mounting evidence has confirmed that essential hypertension (EH) is closely related to low-grade inflammation, but there is still a lack of in-depth understanding of the state of immune cells in the circulating blood of patients with EH. We analyzed whether hypertensive peripheral blood immune cell balance was destroyed. The peripheral blood mononuclear cells (PBMCs) of all subjects were analyzed using time-of-flight cytometry (CyTOF) based on 42 kinds of metal-binding antibodies. CD45+ cells were categorized into 32 kinds of subsets. Compared with the health control (HC) group, the percentage of total dendritic cells, two kinds of myeloid dendritic cell subsets, one intermediate/nonclassical monocyte subset and one CD4+ central memory T cell subset in the EH group, was significantly higher; the percentage of low-density neutrophils, four kinds of classical monocyte subsets, one CD14lowCD16- monocyte subset, one naive CD4+ and one naive CD8+ T cell subsets, one CD4+ effector and one CD4+ central memory T cell subsets, one CD8+ effector memory T cell subset, and one terminally differentiated γδ T cell subset, decreased significantly in EH. What is more, the expression of many important antigens was enhanced in CD45+ immune cells, granulocytes, and B cells in patients with EH. In conclusion, the altered number and antigen expression of immune cells reflect the imbalanced immune state of the peripheral blood in patients with EH.

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“…The study of neutrophils, especially neutrophil heterogeneity, is of great momentousness in the field of cardiovascular and cerebrovascular diseases 201–203 . The normal‐density neutrophils (NDNs) and LDN subpopulations in the peripheral blood of patients with hypertension‐associated chronic inflammation exhibited higher levels of Na + influx and ROS, along with lower levels of apoptosis and stronger proinflammatory ability, thereby promoting the chronic inflammatory response associated with hypertension 204 . Some research teams identified that Ly6G + SiglecF + (Myc + NFϰB + ) neutrophils served as proinflammatory cells in the progression of myocardial infarction (MI) 205,206 .…”

Section: Neutrophil Heterogeneity In Diseasesmentioning

confidence: 99%

The double‐edged role of neutrophil heterogeneity in inflammatory diseases and cancers

Zhou

Cao

et al. 2023

MedComm

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Neutrophils are important immune cells act as the body's first line of defense against infection and respond to diverse inflammatory cues. Many studies have demonstrated that neutrophils display plasticity in inflammatory diseases and cancers. Clarifying the role of neutrophil heterogeneity in inflammatory diseases and cancers will contribute to the development of novel treatment strategies. In this review, we have presented a review on the development of the understanding on neutrophil heterogeneity from the traditional perspective and a high‐resolution viewpoint. A growing body of evidence has confirmed the double‐edged role of neutrophils in inflammatory diseases and tumors. This may be due to a lack of precise understanding of the role of specific neutrophil subsets in the disease. Thus, elucidating specific neutrophil subsets involved in diseases would benefit the development of precision medicine. Thusly, we have summarized the relevance and actions of neutrophil heterogeneity in inflammatory diseases and cancers comprehensively. Meanwhile, we also discussed the potential intervention strategy for neutrophils. This review is intended to deepen our understanding of neutrophil heterogeneity in inflammatory diseases and cancers, while hold promise for precise treatment of neutrophil‐related diseases.

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Heterogeneity of neutrophils in arterial hypertension

Cited by 9 publications

References 36 publications

Low-Density Neutrophils in Healthy Individuals Display a Mature Primed Phenotype

Low-Density Neutrophils in Healthy Individuals Display a Mature Primed Phenotype

Mass Cytometry Reveals the Imbalanced Immune State in the Peripheral Blood of Patients with Essential Hypertension

The double‐edged role of neutrophil heterogeneity in inflammatory diseases and cancers

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