Neutrophils as regulators of cardiovascular inflammation

Silvestre-Roig, Carlos; Braster, Quinte; Ortega‐Gómez, Almudena; Soehnlein, Oliver

doi:10.1038/s41569-019-0326-7

Cited by 338 publications

(357 citation statements)

References 151 publications

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“…Although traditionally considered as a homogeneous population, accumulating evidence has demonstrated their heterogeneity showing the existence of peculiar subsets with phenotypic and functional differences able to display different roles both in homeostatic and pathological conditions [ 86 , 87 ]. Several studies pointed out the central role of neutrophils and their mediators in CVDs, including atherosclerosis, cardiac hypertrophy and fibrosis [ 88 ].…”

Section: Innate Immunity Cells Contribution To Cardiac Fibrosismentioning

confidence: 99%

Innate Immunity Effector Cells as Inflammatory Drivers of Cardiac Fibrosis

Baci

Bosi

Parisi

et al. 2020

IJMS

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Despite relevant advances made in therapies for cardiovascular diseases (CVDs), they still represent the first cause of death worldwide. Cardiac fibrosis and excessive extracellular matrix (ECM) remodeling are common end-organ features in diseased hearts, leading to tissue stiffness, impaired myocardial functional, and progression to heart failure. Although fibrosis has been largely recognized to accompany and complicate various CVDs, events and mechanisms driving and governing fibrosis are still not entirely elucidated, and clinical interventions targeting cardiac fibrosis are not yet available. Immune cell types, both from innate and adaptive immunity, are involved not just in the classical response to pathogens, but they take an active part in “sterile” inflammation, in response to ischemia and other forms of injury. In this context, different cell types infiltrate the injured heart and release distinct pro-inflammatory cytokines that initiate the fibrotic response by triggering myofibroblast activation. The complex interplay between immune cells, fibroblasts, and other non-immune/host-derived cells is now considered as the major driving force of cardiac fibrosis. Here, we review and discuss the contribution of inflammatory cells of innate immunity, including neutrophils, macrophages, natural killer cells, eosinophils and mast cells, in modulating the myocardial microenvironment, by orchestrating the fibrogenic process in response to tissue injury. A better understanding of the time frame, sequences of events during immune cells infiltration, and their action in the injured inflammatory heart environment, may provide a rationale to design new and more efficacious therapeutic interventions to reduce cardiac fibrosis.

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Section: Innate Immunity Cells Contribution To Cardiac Fibrosismentioning

confidence: 99%

Innate Immunity Effector Cells as Inflammatory Drivers of Cardiac Fibrosis

Baci

Bosi

Parisi

et al. 2020

IJMS

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“…Both mature and immature neutrophils are released presumably to meet the high demand for more neutrophils, especially in patients with large MI. Increased systemic levels of G-CSF, the primary regulator of emergency granulopoiesis, [9][10] are likely to drive the production/release of proinflammatory neutrophils from the bone marrow into the circulation. Accordingly, G-CSFmediated immature CD10 neg neutrophil expansion may be an adverse consequence of treating AMI patients with G-CSF.…”

Section: Discussionmentioning

confidence: 99%

“…The significant positive correlation between the frequency of CD10 neg neutrophils and MMP-9/S100A9 serum levels A crucial role for neutrophils in the orchestration of adaptive immunity is emerging. [9][10] In an effort to define the immunoregulatory properties of CD10 neg neutrophils we found that IFNγ production by CD4 + T-cells was increased when co-cultured with CD10 neg neutrophils using a transwell system ( Figure 4C). Thus, normal-density CD10 neg neutrophils from MI patients may modulate CD4 + T-cell immune response in a cell contact-independent manner through soluble factors.…”

Section: Normal-density Cd10 Neg Neutrophils Expand In the Peripheralmentioning

confidence: 99%

Expansion of CD10^negneutrophils and CD14⁺HLA-DR^neg/lowmonocytes driving proinflammatory responses in patients with acute myocardial infarction

Fraccarollo

Neuser

Möller

et al. 2020

Preprint

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BackgroundImmature myeloid cells expand in cancer, autoimmune diseases and viral infection, but their appearance and function after acute myocardial infarction (AMI) remain underexplored.Methods and ResultUsing flow cytometry, cell sorting and a mouse model of ischemia/reperfusion we investigated the role of immature granulocytic/monocytic cells in immune responses post-AMI. Seventy-one patients were categorized into unstable angina (n=11), Non-ST-elevation MI (NSTEMI, n=16), and ST-elevation MI (STEMI, n=44). Circulating CD14+HLA-DRneg/low monocytes and normal-density CD16+CD66b+CD10neg neutrophils are expanded in patients with large AMI and strongly correlated with cardiac damage, function and serum levels of S100A9/S100A8, MMP-9 and IL-1ß. Receiver operating characteristic curve analysis highlighted ability of CD14+HLA-DRneg/low and CD16+CD66b+CD10neg cells in discriminating acute coronary syndromes. CD14+HLA-DRneg/low monocytes did not suppress T-cell proliferation but expressed high amounts of IL1R1 and S100A9. Mechanistically, macrophages differentiated from CD14+HLA-DRneg/low monocytes produced more proinflammatory cytokines upon IFNγ stimulation as CD14+HLA-DRhigh monocyte-derived macrophages. CD10neg neutrophils expressed MMP9 and S100A9 at higher levels compared to CD10pos neutrophils. IFNγ production by CD4+ T-cells was increased in presence of CD10neg neutrophils. Remarkably, elevated circulating IFNγ levels were detected in cytomegalovirus-seropositive patients with expanded CD10neg neutrophils and increased frequency of CD4+CD28null T-cells. Lastly, we showed that murine homologs of human CD10neg neutrophils are Ly6GposCXCR2posCD11bdimCD101neg cells. CD101neg neutrophils are rapidly released into the bloodstream after AMI and migrate to ischemic sites, displaying increased expression of MMP-9 at 3 hours and of IL-1ß at 24 hours after reperfusion.ConclusionCD14+HLA-DRneg/low monocytes and normal-density CD10neg neutrophils inducing proinflammatory immune responses expand in patients with AMI.

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“…Neutrophils release pro-inflammatory molecules, such as TNF-α, IL-1, IL-6, IL-8 and GM-CSF, as well as the pro-oxidant enzyme myeloperoxidase and MMP-8 and MMP-9, further increasing inflammation and setting the stage for plaque disruption, acute thrombosis with subsequent vascular occlusion. 77,78…”

Section: Initiation and Progression Of Atherosclerosis: Role Of Innatmentioning

confidence: 99%

<p>Reflections on Atherosclerosis: Lesson from the Past and Future Research Directions</p>

Minelli

Minelli²,

Montinari³

2020

JMDH

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The clinical manifestations of atherosclerosis are nowadays the main cause of death in industrialized countries, but atherosclerotic disease was found in humans who lived thousands of years ago, before the spread of current risk factors. Atherosclerotic lesions were identified on a 5300-year-old mummy, as well as in Egyptian mummies and other ancient civilizations. For many decades of the twentieth century, atherosclerosis was considered a degenerative disease, mainly determined by a passive lipid storage, while the most recent theory of atherogenesis is based on endothelial dysfunction. The importance of inflammation and immunity in atherosclerosis's pathophysiology was realized around the turn of the millennium, when in 1999 the famous pathologist Russell Ross published in the New England Journal of Medicine an article entitled "Atherosclerosisan inflammatory disease". In the following decades, inflammation has been a topic of intense basic research in atherosclerosis, albeit its importance has ancient scientific roots. In fact, in 1856 Rudolph Virchow was the first proponent of this hypothesis, but evidence of the key role of inflammation in atherogenesis occurred only in 2017. It seemed interesting to retrace the key steps of atherosclerosis in a historical context: from the teachings of the physicians of the Roman Empire to the response-toinjury hypothesis, up to the key role of inflammation and immunity at various stages of disease. Finally, we briefly discussed current knowledge and future trajectories of atherosclerosis research and its therapeutic implications.

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Neutrophils as regulators of cardiovascular inflammation

Cited by 338 publications

References 151 publications

Innate Immunity Effector Cells as Inflammatory Drivers of Cardiac Fibrosis

Innate Immunity Effector Cells as Inflammatory Drivers of Cardiac Fibrosis

Expansion of CD10^negneutrophils and CD14⁺HLA-DR^neg/lowmonocytes driving proinflammatory responses in patients with acute myocardial infarction

<p>Reflections on Atherosclerosis: Lesson from the Past and Future Research Directions</p>

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Neutrophils as regulators of cardiovascular inflammation

Cited by 338 publications

References 151 publications

Innate Immunity Effector Cells as Inflammatory Drivers of Cardiac Fibrosis

Innate Immunity Effector Cells as Inflammatory Drivers of Cardiac Fibrosis

Expansion of CD10negneutrophils and CD14+HLA-DRneg/lowmonocytes driving proinflammatory responses in patients with acute myocardial infarction

<p>Reflections on Atherosclerosis: Lesson from the Past and Future Research Directions</p>

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Expansion of CD10^negneutrophils and CD14⁺HLA-DR^neg/lowmonocytes driving proinflammatory responses in patients with acute myocardial infarction