Neutrophils promote the development of reparative macrophages mediated by ROS to orchestrate liver repair

Yang, Wenting; Tao, Yuandong; Wu, Yan; Zhao, Xinyuan; Ye, Weijie; Zhao, Dianyuan; Fu, Ling; Tian, Caiping; Yang, Jing; He, Fuchu; Tang, Li

doi:10.1038/s41467-019-09046-8

Cited by 262 publications

(242 citation statements)

References 70 publications

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“…Importantly whilst numerous studies have shown that APAP induced liver damage is not driven by neutrophils 55,56 , it is clear that neutrophil activation and hepatic infiltration occurs after APAP induced liver damage 16,57,58 . This neutrophil infiltration is increasingly thought to represent the innate immune reparative response designed to aid a return to hepatic homoeostasis after acute injury 15,59,60 . Our data demonstrate that platelet CLEC-2 deficiency enhances both hepatic neutrophil infiltration and neutrophil phagocytic function.…”

Section: Discussionmentioning

confidence: 99%

The platelet receptor CLEC-2 blocks neutrophil mediated hepatic recovery in acetaminophen induced acute liver failure

et al. 2020

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Acetaminophen (APAP) is the main cause of acute liver failure in the West. Specific efficacious therapies for acute liver failure (ALF) are limited and time-dependent. The mechanisms that drive irreversible acute liver failure remain poorly characterized. Here we report that the recently discovered platelet receptor CLEC-2 (C-type lectin-like receptor) perpetuates and worsens liver damage after toxic liver injury. Our data demonstrate that blocking platelet CLEC-2 signalling enhances liver recovery from acute toxic liver injuries (APAP and carbon tetrachloride) by increasing tumour necrosis factor-α (TNF-α) production which then enhances reparative hepatic neutrophil recruitment. We provide data from humans and mice demonstrating that platelet CLEC-2 influences the hepatic sterile inflammatory response and that this can be manipulated for therapeutic benefit in acute liver injury. Since CLEC-2 mediated platelet activation is independent of major haemostatic pathways, blocking this pathway represents a coagulopathy-sparing, specific and novel therapy in acute liver failure.

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Section: Discussionmentioning

confidence: 99%

The platelet receptor CLEC-2 blocks neutrophil mediated hepatic recovery in acetaminophen induced acute liver failure

et al. 2020

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“…Importantly, recent reports have demonstrated that NO, in association with other ROS, is critically involved in neutrophil extracellular trap (NET) formation [30]. Curiously, it was also recently reported that neutrophils might participate in the resolution of inflammation mediated by reparative macrophages [5]. It has been well established that LPS and inflammatory cytokines stimulate NO production by inducing iNOS expression [31].…”

Section: Discussionmentioning

confidence: 99%

“…LPS signaling through TLR 4 induces macrophage activation by regulating intracellular pathways involved in cytokine, lipid mediator and oxygen reactive species (ROS) production, in a process regulated by calcium signaling [2,3]. The mediators released by activated macrophages play critical roles in neutrophil recruitment and activation, and therefore, influence the progress of immune responses as well as the development of many inflammatory diseases [4,5].…”

Section: Introductionmentioning

confidence: 99%

Curine Inhibits Macrophage Activation and Neutrophil Recruitment in a Mouse Model of Lipopolysaccharide-Induced Inflammation

Ribeiro-Filho

Leite

Calheiros

et al. 2019

Toxins

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Curine is a bisbenzylisoquinoline alkaloid (BBA) with anti-allergic, analgesic, and anti-inflammatory properties. Previous studies have demonstrated that this alkaloid is orally active at non-toxic doses. However, the mechanisms underlying its anti-inflammatory effects remain to be elucidated. This work aimed to investigate the effects of curine on macrophage activation and neutrophil recruitment. Using a murine model of lipopolysaccharide (LPS)-induced pleurisy, we demonstrated that curine significantly inhibited the recruitment of neutrophils in association with the inhibition of cytokines tumor necrosis factor (TNF-α), interleukin (IL)-1β, IL-6, monocyte chemotactic protein (CCL2/MCP-1) as well as leukotriene B4 in the pleural lavage of mice. Curine treatment reduced cytokine levels and the expression of iNOS in in vitro cultures of macrophages stimulated with LPS. Treatment with a calcium channel blocker resulted in comparable inhibition of TNF-α and IL-1β production, as well as iNOS expression by macrophages, suggesting that the anti-inflammatory effects of curine may be related to the inhibition of calcium-dependent mechanisms involved in macrophage activation. In conclusion, curine presented anti-inflammatory effects that are associated with inhibition of macrophage activation and neutrophil recruitment by inhibiting the production of inflammatory cytokines, LTB4 and nitric oxide (NO), and possibly by negatively modulating Ca2+ influx.

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“…This mechanism may not only apply to enhancing the antimicrobial response. For example, it has also been implicated in the stimulation of wound healing through enhancing the differentiation of pro-resolution macrophages in the liver [61].…”

Section: Bacterial Infectionsmentioning

confidence: 99%

Neutrophil Adaptations upon Recruitment to the Lung: New Concepts and Implications for Homeostasis and Disease

Giacalone

Margaroli

Mall

et al. 2020

IJMS

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Neutrophils have a prominent role in all human immune responses against any type of pathogen or stimulus. The lungs are a major neutrophil reservoir and neutrophilic inflammation is a primary response to both infectious and non-infectious challenges. While neutrophils are well known for their essential role in clearance of bacteria, they are also equipped with specific mechanisms to counter viruses and fungi. When these defense mechanisms become aberrantly activated in the absence of infection, this commonly results in debilitating chronic lung inflammation. Clearance of bacteria by phagocytosis is the hallmark role of neutrophils and has been studied extensively. New studies on neutrophil biology have revealed that this leukocyte subset is highly adaptable and fulfills diverse roles. Of special interest is how these adaptations can impact the outcome of an immune response in the lungs due to their potent capacity for clearing infection and causing damage to host tissue. The adaptability of neutrophils and their propensity to influence the outcome of immune responses implicates them as a much-needed target of future immunomodulatory therapies. This review highlights the recent advances elucidating the mechanisms of neutrophilic inflammation, with a focus on the lung environment due to the immense and growing public health burden of chronic lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), and acute lung inflammatory diseases such as transfusion-related acute lung injury (TRALI).

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Neutrophils promote the development of reparative macrophages mediated by ROS to orchestrate liver repair

Cited by 262 publications

References 70 publications

The platelet receptor CLEC-2 blocks neutrophil mediated hepatic recovery in acetaminophen induced acute liver failure

The platelet receptor CLEC-2 blocks neutrophil mediated hepatic recovery in acetaminophen induced acute liver failure

Curine Inhibits Macrophage Activation and Neutrophil Recruitment in a Mouse Model of Lipopolysaccharide-Induced Inflammation

Neutrophil Adaptations upon Recruitment to the Lung: New Concepts and Implications for Homeostasis and Disease

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