Neutrophils orchestrate post-myocardial infarction healing by polarizing macrophages towards a reparative phenotype

Horckmans, Michael; Ring, Larisa; Duchêne, Johan; Santovito, Donato; Schloss, Maximilian J.; Drechsler, Maik; Weber, Christian; Soehnlein, Oliver; Steffens, Sabine

doi:10.1093/eurheartj/ehw002

Cited by 426 publications

(513 citation statements)

References 42 publications

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“…Following AMI, the absence of neutrophils led to decreased MerTK expression in the reparatory macrophages, accumulation of apoptotic cells at the site of the infarction, worsened cardiac function, excessive fibrosis and heart failure 18 . These effects could be reversed by intraperitoneal administration of the protein neutrophil gelatinase-associated lipocalin (NGAL), present in the neutrophil secretome, indicating a crucial role of this protein in the neutrophil-macrophage crosstalk in-vivo (18).…”

Section: Nr4a1mentioning

confidence: 99%

“…Neutrophil depletion led to defective efferocytosis due to decreased expression of the efferocytosis receptor myeloid-epithelial-reproductive receptor tyrosine kinase (MerTK) in anti-inflammatory macrophages infiltrating the infarcted myocardium. The inefficient efferocytosis was associated with excessive deposition of collagen fibers both in the infarcted area and in the remote myocardium (18). Thus, neutrophils are instrumental both in the inflammatory and in the reparatory phase by recruiting monocytes and shifting monocyte-to-macrophage polarization in the myocardium towards a reparatory MerTK hi phenotype.…”

mentioning

confidence: 98%

“…However, this paradigm has recently been changed by the findings of Horckmans et al, showing that neutrophil depletion using an anti-Ly6G antibody (clone 1A8) in a mouse model of AMI surprisingly led to defective myocardial recovery and progressive decline of cardiac function as assessed by echocardiography during the first 2 weeks post-AMI (18). Neutrophil depletion led to defective efferocytosis due to decreased expression of the efferocytosis receptor myeloid-epithelial-reproductive receptor tyrosine kinase (MerTK) in anti-inflammatory macrophages infiltrating the infarcted myocardium.…”

mentioning

confidence: 99%

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Innate Immune Mechanisms in Myocardial Infarction - An Update

Mareş

Marinković

Cotoi

et al. 2018

Revista Romana De Medicina De Laborator

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Section: Nr4a1mentioning

confidence: 99%

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Innate Immune Mechanisms in Myocardial Infarction - An Update

Mareş

Marinković

Cotoi

et al. 2018

Revista Romana De Medicina De Laborator

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“…The precise roles of the various cardiac macrophage subsets either in the steady state or after AMI remain largely unknown. Additionally, the macrophages also communicate with other cell types (such as B cells, neutrophils, and mast cells) to exert further local and remote actions in both tissue injury and repair 50,51 . Leukocyte numbers then return to baseline within 2 weeks in both the heart and blood.…”

Section: Acute Myocardial Infarctionmentioning

confidence: 99%

Erratum: Inflammatory processes in cardiovascular disease: a route to targeted therapies

Ruparelia¹,

Chai²,

Fisher³

et al. 2017

Nat Rev Cardiol

190

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Inflammatory processes are firmly established as central to the development and complications of cardiovascular diseases. Elevated levels of inflammatory markers have been shown to be predictive of future cardiovascular events. The specific targeting of these processes in experimental models has been shown to attenuate myocardial and arterial injury, reduce disease progression, and promote healing. However, the translation of these observations and the demonstration of clear efficacy in clinical practice have been disappointing. A major limitation might be that tools currently used to measure 'inflammation' are insufficiently precise and do not provide information about disease site, activity, or discriminate between functionally important activation pathways. The challenge, therefore, is to make measures of inflammation that are more meaningful, and which can guide specific targeted therapies. In this Review, we consider the roles of inflammatory processes in the related pathologies of atherosclerosis and acute myocardial infarction (AMI), by providing an evaluation of the known and emerging inflammatory pathways. We highlight contemporary techniques to characterize and quantify inflammation, and consider how they might be used to guide specific treatments. Finally, we discuss emerging opportunities in the field, including current limitations and challenges that are the focus of ongoing study.Inflammation and its failure to resolve are firmly established as central to the development and complications of several cardiovascular diseases [1][2][3] . Elevated levels of markers of inflammation, such as C-reactive protein (CRP) and serum amyloid A (SAA), have been shown to be predictive of future cardiovascular events across a range of clinical settings [4][5][6] . The role of the innate immune system in the pathogenesis of cardiovascular diseases has been an area of particular focus, with the appreciation that targeting innate immune function Correspondence to R.P.C.: robin.choudhury@cardiov.ox.ac.uk. Author contributionsAll the authors researched data for the article, discussed its contents, and wrote, reviewed, and edited the manuscript before submission. Competing interests statementThe authors declare no competing interests. HHS Public AccessAuthor manuscript Nat Rev Cardiol. Author manuscript; available in PMC 2017 September 01. Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript in experimental models can variously attenuate disease progression and injury, and promote healing [7][8][9][10] .Processes of inflammation contribute to a broad range of cardiovascular diseases; however, in this Review, we consider the roles of inflammatory processes in the related pathologies of atherosclerosis and acute myocardial infarction (AMI), by providing an evaluation of known and emerging inflammatory pathways that are thought to be central to their pathogenesis, and the consequences of their activation. We highlight contemporary techniques to characterize and quantify inflammation, and consider h...

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“…They can locate in the injured area and contribute to the formation of a fibrin-based provisional matrix [23]. During the adhesion process, the activated platelets release more potent inflammatory and mitogenic substances into the local microenvironment, thereby altering chemotactic, adhesive and proteolytic properties of endothelial cells (ECs) [24] [22]. Moreover, the platelets can trigger the complement activation and play a role in localizing the inflammatory response in the injured area [25].…”

Section: The Effectors Of the Inflammatory Response Plateletsmentioning

confidence: 99%

Cellular recruitment in myocardial ischaemia/reperfusion injury

Bonaventura

Montecucco

Dallegri

2016

Eur J Clin Investigation

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Background Myocardial infarction (MI) is strictly linked to atherosclerosis. Beyond the mechanical narrowing of coronary vessels lumen, during MI a great burden of inflammation is carried out. One of the crucial events is represented by the ischaemia/reperfusion injury, a complex event involving inflammatory cells (such as neutrophils, platelets, monocytes/macrophages, lymphocytes and mast cells) and key activating signals (such as cytokines, chemokines and growth factors). Cardiac repair following myocardial infarction is dependent on a finely regulated response involving a sequential recruitment and the clearance of different subsets of inflammatory cells.

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Neutrophils orchestrate post-myocardial infarction healing by polarizing macrophages towards a reparative phenotype

Cited by 426 publications

References 42 publications

Innate Immune Mechanisms in Myocardial Infarction - An Update

Innate Immune Mechanisms in Myocardial Infarction - An Update

Erratum: Inflammatory processes in cardiovascular disease: a route to targeted therapies

Cellular recruitment in myocardial ischaemia/reperfusion injury

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