Alternatively activated macrophages promote resolution of necrosis following acute liver injury

Lewis, Philip Starkey; Campana, Lara; Aleksieva, Niya; Cartwright, Jennifer A; MacKinnon, Alison C.; O’Duibhir, Eoghan; Kendall, Timothy J.; Vermeren, Matthieu; Thomson, Adrian; Gadd, Victoria L.; Dwyer, Benjamin J.; Aird, Rhona; Man, Tak Yung; Rossi, Adriano G.; Forrester, Lesley M.; Park, B. Kevin; Forbes, Stuart J.

doi:10.1016/j.jhep.2020.02.031

Cited by 129 publications

(117 citation statements)

References 42 publications

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“…49,76,141 Expression of these genes enables wound healing, clearance of dead cells, and promotion of hepatocyte proliferation, thereby allowing the liver to return to homeostasis after injury and fibrosis. 49,139,142,143 In mice challenged by APAP overdose, preventing monocyte infiltration by neutralization of CCR2 results in the absence of Ly6C low MoMϕs and thus a lack of tissue inflammation resolution and the accumulation of late apoptotic neutrophils. 143 Conversely, injection of BM-derived alternative activated macrophages, which are primarily Ly6C low MoMϕs, stimulates hepatocyte proliferation and accelerates recovery of the liver from APAP-induced necrosis.…”

Section: Roles Of Macrophages In Resolving Inflammation During Liver mentioning

confidence: 99%

“…143 Conversely, injection of BM-derived alternative activated macrophages, which are primarily Ly6C low MoMϕs, stimulates hepatocyte proliferation and accelerates recovery of the liver from APAP-induced necrosis. 142 Phagocytosis of dead cells (efferocytosis) is a major mechanism that promotes the switch of Ly6C high MoMϕs to Ly6C low MoMϕs (Fig. 1).…”

Section: Roles Of Macrophages In Resolving Inflammation During Liver mentioning

confidence: 99%

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Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities

et al. 2020

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Macrophages, which are key cellular components of the liver, have emerged as essential players in the maintenance of hepatic homeostasis and in injury and repair processes in acute and chronic liver diseases. Upon liver injury, resident Kupffer cells (KCs) sense disturbances in homeostasis, interact with hepatic cell populations and release chemokines to recruit circulating leukocytes, including monocytes, which subsequently differentiate into monocyte-derived macrophages (MoMϕs) in the liver. Both KCs and MoMϕs contribute to both the progression and resolution of tissue inflammation and injury in various liver diseases. The diversity of hepatic macrophage subsets and their plasticity explain their different functional responses in distinct liver diseases. In this review, we highlight novel findings regarding the origins and functions of hepatic macrophages and discuss the potential of targeting macrophages as a therapeutic strategy for liver disease.

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Section: Roles Of Macrophages In Resolving Inflammation During Liver mentioning

confidence: 99%

Section: Roles Of Macrophages In Resolving Inflammation During Liver mentioning

confidence: 99%

Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities

et al. 2020

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“…In an experimental model of acute liver injury, adoptive transfer of ex vivo IL-4/IL-13-polarized BMDM rapidly reduced liver injury and several mediators of inflammation. 163 Of note, the adoptive transfer of primary humanpolarized monocyte-derived MФ partially recapitulated the therapeutic effect observed with polarized mouse BMDM in the same mouse model. 163 Similarly, injection of BMDM or embryonic stem cell-derived MФ reduced both fibrosis and improved liver regeneration in a hepatic injury and fibrosis model.…”

Section: Adoptive Transfermentioning

confidence: 84%

Macrophage reprogramming for therapy

et al. 2021

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Dysfunction of the immune system underlies a plethora of human diseases, requiring the development of immunomodulatory therapeutic intervention. To date, most strategies employed have been focusing on the modification of T lymphocytes, and although remarkable improvement has been obtained, results often fall short of the intended outcome. Recent cutting-edge technologies have highlighted macrophages as potential targets for disease control. Macrophages play central roles in development, homeostasis and host defence, and their dysfunction and dysregulation have been implicated in the onset and pathogenesis of multiple disorders including cancer, neurodegeneration, autoimmunity and metabolic diseases. Recent advancements have led to a greater understanding of macrophage origin, diversity and function, in both health and disease. Over the last few years, a variety of strategies targeting macrophages have been developed and these open new therapeutic opportunities. Here, we review the progress in macrophage reprogramming in various disorders and discuss the potential implications and challenges for macrophage-targeted approaches in human disease.

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“…This reveals possible communication signals between macrophage subpopulations. 28 In addition, elucidation of neutrophil-macrophage interactions has shown that ROS secreted by neutrophils orchestrate the switch to proresolving macrophages. This shows that ROS, primarily known for their role in the initiation of inflammation, also have resolution-inducing effects.…”

Section: Macrophagesmentioning

confidence: 99%

“…The therapeutic efficacy was partially replicated with the use of human-derived alternatively activated macrophages in mice and its potential as a novel therapy is intriguing. 28 Interestingly, a recent study has shown the efficacy of administrating classically activated macrophages ("M1") in the amelioration of CCl4 or BDLinduced liver fibrosis. They exhibited stronger therapeutic effects when compared with the administration of nonpolarized ("M0") or alternative activated macrophages ("M2").…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Novel Mechanisms for Resolution of Liver Inflammation: Therapeutic Implications

et al. 2021

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Traditional concepts have classically viewed resolution of inflammation as a passive process yet insight into the pathways by which inflammation is resolved has challenged this idea. Resolution has been revealed as a highly dynamic and active event that is essential to counteract the dysregulated inflammatory response that drives diverse disease states. Abrogation of the hepatic inflammatory response through the stimulation of proresolving mechanisms represents a new paradigm in the setting of chronic inflammatory-driven liver diseases. Elucidation of the role of different cells of the innate and adaptive immune system has highlighted the interplay between them as an important orchestrator of liver repair. A finely tuned interaction between neutrophils and macrophages has risen as revolutionary mechanism that drives the restoration of hepatic function and architecture. Specialized proresolving mediators have also been shown to act as stop signals of the inflammatory response and promote resolution as well as tissue regeneration. In this review, we discuss the discovery and understanding of the mechanisms by which inflammation is resolved and highlight novel proresolving pathways that represent promising therapeutic strategies.

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Alternatively activated macrophages promote resolution of necrosis following acute liver injury

Cited by 129 publications

References 42 publications

Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities

Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities

Macrophage reprogramming for therapy

Novel Mechanisms for Resolution of Liver Inflammation: Therapeutic Implications

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