Macrophage Polarization: Different Gene Signatures in M1(LPS+) vs. Classically and M2(LPS–) vs. Alternatively Activated Macrophages

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: May 24, 2019

Macrophages are found in tissues, body cavities, and mucosal surfaces. Most tissue macrophages seeded the early embryo before definitive hematopoiesis is established. Others derived from blood monocytes. The macrophage lineage diversification plasticity key aspects of their functionality. can also be generated monocytes vitro undergo classical (LPS+IFN-γ) or alternative (IL-4) activation. In vivo, with different polarization activation markers coexist tissues. Certain mouse strains preferentially promote T-helper-1 (Th1) responses other Th2 responses. Their induce iNOS arginase have been called M1 M2, respectively. many publications, classically activated M2 alternatively used interchangeably. We tested whether this justified by comparing gene lists positively [M1(=LPS+)] negatively [M2(=LPS-)] correlated ratio IL-12 1 transcriptomes LPS-treated peritoneal (LPS, IFN-γ) versus bone marrow-derived macrophages, both published datasets. Although there some overlap between vivo M1(=LPS+) (LPS+IFNγ) M2(=LPS-) more genes regulated opposite unrelated ways. Thus, not equivalent to activated, macrophages. This fundamental discrepancy explains why most surface identified on do translate situation. Valid M1/M2 remain discovered.

Language: Английский

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The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes

Frontiers in Physiology, Journal Year: 2018, Volume and Issue: 9

Published: May 1, 2018

Macrophages play key roles in all phases of adult wound healing, which are inflammation, proliferation and remodeling. As wounds heal, the local macrophage population transitions from predominantly pro-inflammatory (M1-like phenotypes) to anti-inflammatory (M2-like phenotypes). Non-healing chronic wounds, such as pressure, arterial, venous diabetic ulcers indefinitely remain inflammation—the first stage healing. Thus, macrophages retain characteristics. This review discusses physiology monocytes acute healing different phenotypes described literature for both vitro vivo models. We also discuss aberrations that occur populations attempts restore function by therapeutic approaches. These include endogenous M1 attenuation, exogenous M2 supplementation modulation/M2 promotion via mesenchymal stem cells, growth factors, biomaterials, heme oxygenase-1 (HO-1) expression oxygen therapy. recognize challenges controversies exist this field, standardization phenotype nomenclature, definition their distinct understanding is optimal order promote wounds.

Language: Английский

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Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities

Nature Reviews Cardiology, Journal Year: 2019, Volume and Issue: unknown

Published: March 7, 2019

Language: Английский

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IL-6 in inflammation, autoimmunity and cancer

International Immunology, Journal Year: 2020, Volume and Issue: 33(3), P. 127 - 148

Published: Dec. 15, 2020

IL-6 is involved both in immune responses and inflammation, hematopoiesis, bone metabolism embryonic development. plays roles chronic inflammation (closely related to inflammatory diseases, autoimmune diseases cancer) even the cytokine storm of corona virus disease 2019 (COVID-19). Acute during response wound healing a well-controlled response, whereas are uncontrolled responses. Non-immune cells, cytokines such as IL-1β, tumor necrosis factor alpha (TNFα) transcription factors nuclear factor-kappa B (NF-κB) signal transducer activator 3 (STAT3) play central inflammation. Synergistic interactions between NF-κB STAT3 induce hyper-activation followed by production various cytokines. Because an target, simultaneous activation non-immune cells triggers positive feedback loop IL-6-STAT3 axis. This called amplifier (IL-6 Amp) key player local initiation model, which states that initiators, senescence, obesity, stressors, infection, injury smoking, trigger promoting cells. model counters dogma holds autoimmunity oncogenesis triggered breakdown tissue-specific tolerance oncogenic mutations, respectively. The Amp activated variety demonstrating axis critical target for treating diseases.

Language: Английский

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Implications of macrophage polarization in autoimmunity

Immunology, Journal Year: 2018, Volume and Issue: 154(2), P. 186 - 195

Published: Feb. 18, 2018

Macrophages are extremely heterogeneous and plastic cells with an important role not only in physiological conditions, but also during inflammation (both for initiation resolution). In the early 1990s, two different phenotypes of macrophages were described: one them called classically activated (or inflammatory) (M1) other alternatively wound-healing) (M2). Currently, it is known that functional polarization into groups over-simplified description macrophage heterogeneity plasticity; indeed, necessary to consider a continuum states. Overall, current available data indicate multifactorial process which huge number factors can be involved producing activation scenarios. Once adopts phenotype, still retains ability continue changing response new environmental influences. The reversibility has critical therapeutic value, especially diseases M1/M2 imbalance plays pathogenic role. this review, we assess high plasticity their potential exploited reduce chronic/detrimental inflammation. On whole, evidence detailed review underscores as target interest immunotherapy.

Language: Английский

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Mitochondrial Dysfunction Prevents Repolarization of Inflammatory Macrophages

Cell Reports, Journal Year: 2016, Volume and Issue: 17(3), P. 684 - 696

Published: Oct. 1, 2016

Highlights•Mouse and human M1 macrophages fail to repolarize M2 upon IL-4 restimulation•LPS + IFNγ treatment inhibits mitochondrial oxidative respiration in macrophages•Mitochondrial function is required for the repolarization an phenotype•NO blunts prevents plasticity macrophagesSummaryMacrophages are innate immune cells that adopt diverse activation states response their microenvironment. Editing macrophage dampen inflammatory diseases by promoting of (M1) anti-inflammatory (M2) high interest. Here, we find mouse convert into exposure vitro vivo. In sharp contrast, more plastic readily repolarized state. We identify M1-associated inhibition phosphorylation as factor responsible preventing M1→M2 repolarization. Inhibiting nitric oxide production, a key effector molecule cells, dampens decline improve metabolic phenotypic reprogramming macrophages. Thus, phosphorylation, thereby Therapeutically restoring might be useful control disease.Graphical abstract

Language: Английский

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Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(20), P. 7794 - 7794

Published: Oct. 21, 2020

Emerging autologous cellular therapies that utilize platelet-rich plasma (PRP) applications have the potential to play adjunctive roles in a variety of regenerative medicine treatment plans. There is global unmet need for tissue repair strategies treat musculoskeletal (MSK) and spinal disorders, osteoarthritis (OA), patients with chronic complex recalcitrant wounds. PRP therapy based on fact platelet growth factors (PGFs) support three phases wound healing cascade (inflammation, proliferation, remodeling). Many different formulations been evaluated, originating from human, vitro, animal studies. However, recommendations vitro research often lead clinical outcomes because it difficult translate non-clinical study methodology human protocols. In recent years, progress has made understanding technology concepts bioformulation, new directives indications suggested. this review, we will discuss developments regarding preparation composition dosing, leukocyte activities concerning innate adaptive immunomodulation, serotonin (5-HT) effects, pain killing. Furthermore, mechanisms related inflammation angiogenesis processes. Lastly, review effect certain drugs activity, combination rehabilitation

Language: Английский

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Progress in tumor-associated macrophage (TAM)-targeted therapeutics

Advanced Drug Delivery Reviews, Journal Year: 2017, Volume and Issue: 114, P. 206 - 221

Published: April 25, 2017

Language: Английский

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Monocyte and Macrophage Plasticity in Tissue Repair and Regeneration

American Journal Of Pathology, Journal Year: 2015, Volume and Issue: 185(10), P. 2596 - 2606

Published: June 27, 2015

Language: Английский

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Promoting tissue regeneration by modulating the immune system

Acta Biomaterialia, Journal Year: 2017, Volume and Issue: 53, P. 13 - 28

Published: Jan. 22, 2017

The immune system plays a central role in tissue repair and regeneration. Indeed, the response to injury is crucial determining speed outcome of healing process, including extent scarring restoration organ function. Therefore, controlling components via biomaterials drug delivery systems becoming an attractive approach regenerative medicine, since therapies based on stem cells growth factors have not yet proven be broadly effective clinic. To integrate into strategies, one first challenges understand precise functions different during process. While remarkable progress has been made, mechanisms involved are still elusive, there indication for both negative positive roles depending type or life stage. It well recognized that innate comprising danger signals, neutrophils macrophages modulates healing. In addition, it evident adaptive response, particular T cell subset activities, critical role. this review, we present overview basic Then, highlight various approaches aim at modulating these limit fibrosis promote We propose next generation may evolve from typical biomaterial-, cell-, factor-centric immune-centric approach. Most strategies safe reasonably efficient addition factors, Here, immune-mediated regeneration support existing could alternative using factors. part review key process marks them as potential target designing strategies. second part, discuss

Language: Английский

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