scholarly journals Biodegradation of graphdiyne oxide in classically activated (M1) macrophages modulates cytokine production

Nanoscale ◽  
2021 ◽  
Author(s):  
Guotao Peng ◽  
Tianbo Duan ◽  
Mengyu Guo ◽  
Yurui Xue ◽  
Chunying Chen ◽  
...  
Keyword(s):  
Cytokine Production ◽  
M1 Macrophages ◽  
Primary Monocyte ◽  
Potential Biodegradability ◽  
Classically Activated ◽  
Carbon Based

Graphdiyne oxide (GDYO) is a carbon‐based nanomaterial possessing sp2 and sp-hybridized carbon atoms with many promising applications. However, its biocompatibility and potential biodegradability remain poorly understood. Using human primary monocyte-derived...

scholarly journals Macrophages in Tumor Microenvironments and the Progression of Tumors

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Ning-Bo Hao ◽  
Mu-Han Lü ◽  
Ya-Han Fan ◽  
Ya-Ling Cao ◽  
Zhi-Ren Zhang ◽  
...  
Keyword(s):  
Adaptive Immune Response ◽  
M2 Macrophages ◽  
Tumor Associated Macrophages ◽  
M1 Macrophages ◽  
Tumor Microenvironments ◽  
Adaptive Immune ◽  
Immunosuppressive Microenvironment ◽  
Inflammatory Molecules ◽  
Alternatively Activated ◽  
Classically Activated

Macrophages are widely distributed innate immune cells that play indispensable roles in the innate and adaptive immune response to pathogens and in-tissue homeostasis. Macrophages can be activated by a variety of stimuli and polarized to functionally different phenotypes. Two distinct subsets of macrophages have been proposed, including classically activated (M1) and alternatively activated (M2) macrophages. M1 macrophages express a series of proinflammatory cytokines, chemokines, and effector molecules, such as IL-12, IL-23, TNF-α, iNOS and MHCI/II. In contrast, M2 macrophages express a wide array of anti-inflammatory molecules, such as IL-10, TGF-β, and arginase1. In most tumors, the infiltrated macrophages are considered to be of the M2 phenotype, which provides an immunosuppressive microenvironment for tumor growth. Furthermore, tumor-associated macrophages secrete many cytokines, chemokines, and proteases, which promote tumor angiogenesis, growth, metastasis, and immunosuppression. Recently, it was also found that tumor-associated macrophages interact with cancer stem cells. This interaction leads to tumorigenesis, metastasis, and drug resistance. So mediating macrophage to resist tumors is considered to be potential therapy.

scholarly journals UK5099 inhibits macrophage activation independent of mitochondrial pyruvate carrier mediated metabolism

2021 ◽  
Author(s):  
Linyu Ran ◽  
Song Zhang ◽  
Pei Zhao ◽  
Jiaqi Zhou ◽  
Haiyun Gan ◽  
...  
Keyword(s):  
Macrophage Activation ◽  
Cytokine Production ◽  
Inflammatory Responses ◽  
Tca Cycle ◽  
Metabolic Reprogramming ◽  
M1 Macrophages ◽  
Inflammatory Cytokine Production ◽  
The Tca Cycle ◽  
Mitochondrial Pyruvate Carrier ◽  
High Doses

Abstract Glycolysis is essential for the classical activation of macrophages (M1), but how glycolytic pathway metabolites engage in this process remains to be elucidated. Glycolysis culminates in the production of pyruvate, which can be transported into the mitochondria by the mitochondrial pyruvate carrier (MPC) followed by conversion to citrate and utilization in the TCA cycle. Alternatively, pyruvate can be metabolized to lactate under aerobic conditions, which had been considered to be the dominant route in the setting of classical macrophage activation. However, based on studies that used UK5099 as a MPC inhibitor and showed reduction in key inflammatory cytokines, the mitochondrial route has been considered to be of significance for M1 activation as well. Herein, using a genetic depletion model, we found that MPC is dispensable for metabolic reprogramming and the activation of M1. While UK5099 reaches maximal MPC inhibitory capacity at approximately 2–5µM, higher concentrations are required to inhibit inflammatory cytokine production in M1 and this is independent of MPC expression. Apart from MPC inhibition, UK5099 at high doses impairs glutamate oxidation, mitochondrial membrane potential and HIF-1α stabilization. Taken together, UK5099 inhibits inflammatory responses in M1 macrophages due to effects other than MPC inhibition.

scholarly journals Macrophage Innate Training Induced by IL-4 Activation Enhances OXPHOS Driven Anti-Mycobacterial Responses

2021 ◽  
Author(s):  
Mimmi L. E. Lundahl ◽  
Morgane Mitermite ◽  
Dylan G. Ryan ◽  
Niamh C. Williams ◽  
Ming Yang ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Mycobacterial Infection ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Cytokine Responses ◽  
M1 Macrophage ◽  
Mycobacterial Growth ◽  
Insight Into ◽  
Alternatively Activated ◽  
Classically Activated

AbstractMacrophages are key innate immune cells for determining the outcome of Mycobacterium tuberculosis infection. Polarization with IFNγ and LPS into the “classically activated” M1 macrophage enhances pro-inflammatory and microbicidal responses, important for eradicating the bacterium. By contrast, “alternatively activated” M2 macrophages, polarized with IL-4, oppose bactericidal mechanisms and allow mycobacterial growth. These activation states are accompanied by distinct metabolic profiles, where M1 macrophages favor near exclusive use of glycolysis, whereas M2 macrophages up-regulate oxidative phosphorylation (OXPHOS). Here we demonstrate that activation with IL-4 counterintuitively induces protective innate memory against mycobacterial challenge. This was associated with enhanced pro-inflammatory cytokine responses and killing capacity. Moreover, despite this switch towards a phenotype that is more akin to classical activation, IL-4 trained macrophages do not demonstrate M1-typical metabolism, instead retaining heightened use of OXPHOS. Moreover, inhibition of OXPHOS with oligomycin, 2-deoxy glucose or BPTES all impeded heightened pro-inflammatory cytokine responses from IL-4 trained macrophages. Lastly, this work identifies that IL-10 negatively regulates protective IL-4 training, impeding pro-inflammatory and bactericidal mechanisms. In summary, this work provides new and unexpected insight into alternative macrophage activation states in the context of mycobacterial infection.

scholarly journals Macrophages in Atherosclerosis Regression

2020 ◽  
Vol 40 (1) ◽  
pp. 20-33 ◽  
Author(s):  
Tessa J. Barrett
Keyword(s):  
Atherosclerotic Cardiovascular Disease ◽  
Murine Models ◽  
Peripheral Artery ◽  
M1 Macrophages ◽  
Local Inflammatory Response ◽  
Plaque Development ◽  
Artery Disease ◽  
Plaque Macrophage ◽  
Alternatively Activated ◽  
Classically Activated

Macrophages play a central role in the development of atherosclerotic cardiovascular disease (ASCVD), which encompasses coronary artery disease, peripheral artery disease, cerebrovascular disease, and aortic atherosclerosis. In each vascular bed, macrophages contribute to the maintenance of the local inflammatory response, propagate plaque development, and promote thrombosis. These central roles, coupled with their plasticity, makes macrophages attractive therapeutic targets in stemming the development of and stabilizing existing atherosclerosis. In the context of ASCVD, classically activated M1 macrophages initiate and sustain inflammation, and alternatively activated M2 macrophages resolve inflammation. However, this classification is now considered an oversimplification, and a greater understanding of plaque macrophage physiology in ASCVD is required to aid in the development of therapeutics to promote ASCVD regression. Reviewed herein are the macrophage phenotypes and molecular regulators characteristic of ASCVD regression, and the current murine models of ASCVD regression.

scholarly journals BTN2A2 protein negatively regulates T cells to ameliorate collagen-induced arthritis in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xueping He ◽  
Rong Hu ◽  
Peng Luo ◽  
Jie Gao ◽  
Wenjiang Yang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytokine Production ◽  
Inflammatory Responses ◽  
Autoimmune Disorder ◽  
Collagen Induced Arthritis ◽  
M1 Macrophages ◽  
Cell Functions ◽  
Th17 Cytokine

AbstractRheumatoid arthritis (RA) is an autoimmune disorder characterized by persistent inflammatory responses in target tissues and organs, resulting in the destruction of joints. Collagen type II (CII)-induced arthritis (CIA) is the most used animal model for human RA. Although BTN2A2 protein has been previously shown to inhibit T cell functions in vitro, its effect on autoimmune arthritis has not been reported. In this study, we investigate the ability of a recombinant BTN2A2-IgG2a Fc (BTN2A2-Ig) fusion protein to treat CIA. We show here that administration of BTN2A2-Ig attenuates established CIA, as compared with control Ig protein treatment. This is associated with reduced activation, proliferation and Th1/Th17 cytokine production of T cells in BTN2A2-Ig-treated CIA mice. BTN2A2-Ig also inhibits CII-specific T cell proliferation and Th1/Th17 cytokine production. Although the percentage of effector T cells is decreased in BTN2A2-Ig-treated CIA mice, the proportions of naive T cells and regulatory T cells is increased. Furthermore, BTN2A2-Ig reduces the percentage of proinflammatory M1 macrophages but increases the percentage of anti-inflammatory M2 macrophages in the CIA mice. Our results suggest that BTN2A2-Ig protein has the potential to be used in the treatment of collagen-induced arthritis models.

SEM Cold Stage Techniques for the Observation of Vegetative and Floral Apices of Oat (Avena sativa L.) Plants

1977 ◽  
Vol 35 ◽  
pp. 590-591
Author(s):  
B. K. Kirchoff ◽  
L.F. Allard ◽  
W.C. Bigelow
Keyword(s):  
Critical Point ◽  
Avena Sativa ◽  
Substantial Improvement ◽  
Fresh Tissue ◽  
Cold Stage ◽  
Critical Point Drying ◽  
Almost All ◽  
Cell Collapse ◽  
Conductive Paint ◽  
Carbon Based

In attempting to use the SEM to investigate the transition from the vegetative to the floral state in oat (Avena sativa L.) it was discovered that the procedures of fixation and critical point drying (CPD), and fresh tissue examination of the specimens gave unsatisfactory results. In most cases, by using these techniques, cells of the tissue were collapsed or otherwise visibly distorted. Figure 1 shows the results of fixation with 4.5% formaldehyde-gluteraldehyde followed by CPD. Almost all cellular detail has been obscured by the resulting shrinkage distortions. The larger cracks seen on the left of the picture may be due to dissection damage, rather than CPD. The results of observation of fresh tissue are seen in Fig. 2. Although there is a substantial improvement over CPD, some cell collapse still occurs.Due to these difficulties, it was decided to experiment with cold stage techniques. The specimens to be observed were dissected out and attached to the sample stub using a carbon based conductive paint in acetone.

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