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 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 Immune Response to COVID-19

2021 ◽  
Author(s):  
Ricardo Wesley Alberca
Keyword(s):  
Immune Response ◽  
Adaptive Immune Response ◽  
Multiple Organ ◽  
Disease Course ◽  
Angiotensin Converting Enzyme 2 ◽  
Damage And Failure ◽  
Adaptive Immune ◽  
General Aspects ◽  
Inflammatory Molecules ◽  
The Impact

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) invades the host’s cells via the angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). ACE2 and TMPRSS2 molecules are highly expressed on the respiratory tract but are also expressed in other organs such as kidneys, heart, and intestine, which could partially explain the multiple organ infection, damage, and failure. During the COVID-19 disease course, patients may develop a dysregulation in the immune response, with an exacerbated production of pro-inflammatory molecules and hypercoagulation, which can collaborate to the increase in tissue damage and death. This chapter will cover general aspects of the innate and adaptive immune response during COVID-19, the impact of comorbidities on the immune response to SARS-CoV-2, and the immune response generated by COVID-19 vaccines.

scholarly journals Deactivation of 12(S)-HETE through (ω-1)-hydroxylation and β-oxidation in alternatively activated macrophages

2018 ◽  
Vol 59 (4) ◽  
pp. 615-624 ◽  
Author(s):  
Tamas Kriska ◽  
Michael J. Thomas ◽  
John R. Falck ◽  
William B. Campbell
Keyword(s):  
Cytochrome P450 ◽  
Angiotensin Ii ◽  
Oxidation Products ◽  
Eicosatetraenoic Acid ◽  
Pcr Analysis ◽  
Experimental Hypertension ◽  
M2 Macrophages ◽  
Cytochrome P450 Enzymes ◽  
M1 Macrophages ◽  
Alternatively Activated

Polarization of macrophages to proinflammatory M1 and to antiinflammatory alternatively activated M2 states has physiological implications in the development of experimental hypertension and other pathological conditions. 12/15-Lipoxygenase (12/15-LO) and its enzymatic products 12(S)- and 15(S)-hydroxyeicosatetraenoic acid (HETE) are essential in the process since disruption of the gene encoding 12/15-LO renders the mice unsusceptible to hypertension. The objective was to test the hypothesis that M2 macrophages catabolize 12(S)-HETE into products that are incapable of promoting vasoconstriction. Cultured M2 macrophages metabolized externally added [14C]12(S)-HETE into more polar metabolites, while M1 macrophages had little effect on the catabolism. The major metabolites were identified by mass spectrometry as (ω-1)-hydroxylation and β-oxidation products. The conversion was inhibited by both peroxisomal β-oxidation inhibitor, thioridazine, and cytochrome P450 inhibitors. Quantitative PCR analysis confirmed that several cytochrome P450 enzymes (CYP2E1 and CYP1B1) and peroxisomal β-oxidation markers were upregulated upon M2 polarization. The identified 12,19-dihydroxy-5,8,10,14-eicosatetraenoic acid and 8-hydroxy-6,10-hexadecadienoic acid metabolites were tested on abdominal aortic rings for biological activity. While 12(S)-HETE enhanced vasoconstrictions to angiotensin II from 15% to 25%, the metabolites did not. These results indicate that M2, but not M1, macrophages degrade 12(S)-HETE into products that no longer enhance the angiotensin II-induced vascular constriction, supporting a possible antihypertensive role of M2 macrophages.

scholarly journals Tumor-Associated Macrophages in Glioma: Friend or Foe?

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Benjamin C. Kennedy ◽  
Christopher R. Showers ◽  
David E. Anderson ◽  
Lisa Anderson ◽  
Peter Canoll ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Glioma Cell ◽  
Gene Array ◽  
Tumor Development ◽  
Tumor Promotion ◽  
Tumor Associated Macrophages ◽  
And Function ◽  
M1 Type ◽  
Alternatively Activated ◽  
Classically Activated

Tumor-associated macrophages (TAMs) contribute substantially to the tumor mass of gliomas and have been shown to play a major role in the creation of a tumor microenvironment that promotes tumor progression. Shortcomings of attempts at antiglioma immunotherapy may result from a failure to adequately address these effects. Emerging evidence supports an independent categorization of glioma TAMs as alternatively activated M2-type macrophages, in contrast to classically activated proinflammatory M1-type macrophages. These M2-type macrophages exert glioma-supportive effects through reduced anti-tumor functions, increased expression of immunosuppressive mediators, and nonimmune tumor promotion through expression of trophic and invasion-facilitating substances. Much of our work has demonstrated these features of glioma TAMs, and together with the supporting literature will be reviewed here. Additionally, the dynamics of glioma cell-TAM interaction over the course of tumor development remain poorly understood; our efforts to elucidate glioma cell-TAM dynamics are summarized. Finally, the molecular pathways which underlie M2-type TAM polarization and gene expression similarly require further investigation, and may present the most potent targets for immunotherapeutic intervention. Highlighting recent evidence implicating the transcription factor STAT3 in immunosuppressive tumorigenic glioma TAMs, we advocate for gene array-based approaches to identify yet unappreciated expression regulators and effector molecules important to M2-type glioma TAMs polarization and function within the glioma tumor microenvironment.

scholarly journals Moonlighting Proteins Are Important Players in Cancer Immunology

2021 ◽  
Vol 11 ◽  
Author(s):  
Annalisa Adamo ◽  
Cristina Frusteri ◽  
Maria Teresa Pallotta ◽  
Tracey Pirali ◽  
Silvia Sartoris ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Immune Cells ◽  
Adaptive Immune Response ◽  
Decisive Role ◽  
Cancer Therapies ◽  
Immunological Responses ◽  
Adaptive Immune ◽  
Anti Cancer ◽  
Moonlighting Proteins ◽  
Immunosuppressive Microenvironment

Plasticity and adaptation to environmental stress are the main features that tumor and immune system share. Except for intrinsic and high-defined properties, cancer and immune cells need to overcome the opponent’s defenses by activating more effective signaling networks, based on common elements such as transcriptional factors, protein-based complexes and receptors. Interestingly, growing evidence point to an increasing number of proteins capable of performing diverse and unpredictable functions. These multifunctional proteins are defined as moonlighting proteins. During cancer progression, several moonlighting proteins are involved in promoting an immunosuppressive microenvironment by reprogramming immune cells to support tumor growth and metastatic spread. Conversely, other moonlighting proteins support tumor antigen presentation and lymphocytes activation, leading to several anti-cancer immunological responses. In this light, moonlighting proteins could be used as promising new potential targets for improving current cancer therapies. In this review, we describe in details 12 unprecedented moonlighting proteins that during cancer progression play a decisive role in guiding cancer-associated immunomodulation by shaping innate or adaptive immune response.

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 Defects in Macrophage Reprogramming in Cancer Therapy: The Negative Impact of PD-L1/PD-1

2021 ◽  
Vol 12 ◽  
Author(s):  
Hao Cai ◽  
Yichi Zhang ◽  
Jian Wang ◽  
Jinyang Gu
Keyword(s):  
Cancer Therapy ◽  
Negative Impact ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Programmed Death ◽  
Antigen Presenting ◽  
Cell Death Protein ◽  
Alternatively Activated

Classically activated M1 macrophages and alternatively activated M2 macrophages are two polarized subsets of macrophages at the extreme ends of a constructed continuum. In the field of cancer research, M2 macrophage reprogramming is defined as the repolarization of pro-tumoral M2 to anti-tumoral M1 macrophages. It is known that colony-stimulating factor 1 (CSF1)/CSF1 receptor (CSF1R) and CSF2/CSF2R signaling play important roles in macrophage polarization. Targeting CSF1/CSF1R for M2 macrophage reprogramming has been widely performed in clinical trials for cancer therapy. Other targets for M2 macrophage reprogramming include Toll-like receptor 7 (TLR7), TLR8, TLR9, CD40, histone deacetylase (HDAC), and PI3Kγ. Although macrophages are involved in innate and adaptive immune responses, M1 macrophages are less effective at phagocytosis and antigen presenting, which are required properties for the activation of T cells and eradication of cancer cells. Similar to T and dendritic cells, the “functionally exhausted” status might be attributed to the high expression of programmed death-ligand 1 (PD-L1) or programmed cell death protein 1 (PD-1). PD-L1 is expressed on both M1 and M2 macrophages. Macrophage reprogramming from M2 to M1 might increase the expression of PD-L1, which can be transcriptionally activated by STAT3. Macrophage reprogramming or PD-L1/PD-1 blockade alone is less effective in the treatment of most cancers. Since PD-L1/PD-1 blockade could make up for the defect in macrophage reprogramming, the combination of macrophage reprogramming and PD-L1/PD-1 blockade might be a novel treatment strategy for cancer therapy.

scholarly journals The impact of macrophage-cancer cell interaction on the efficacy of photodynamic therapy

2015 ◽  
Vol 14 (8) ◽  
pp. 1403-1409 ◽  
Author(s):  
Mladen Korbelik ◽  
Michael R. Hamblin
Keyword(s):  
Immune Response ◽  
Photodynamic Therapy ◽  
Tumor Cells ◽  
Adaptive Immune Response ◽  
Cell Interaction ◽  
M1 Macrophages ◽  
Adaptive Immune ◽  
Light Delivery ◽  
Dying Cells ◽  
The Impact

PDT has different effects on macrophages in tumors. The photosensitizer (PS) is taken up by M2 TAMS inside the tumor, which are killed upon light delivery. Signaling from these dying cells attracts new M1 macrophages from the circulation that can kill remaining tumor cells and stimulate an adaptive immune response.

M2 Macrophages but not M1 Macrophages Are Associated with Worst Outcome in Classical Hodgkin Lymphoma

2014 ◽  
Vol 226 (02) ◽  
Author(s):  
M Barros ◽  
P Segges ◽  
G Vera-Lozada ◽  
R Hassan ◽  
G Niedobitek
Keyword(s):  
Hodgkin Lymphoma ◽  
M2 Macrophages ◽  
Classical Hodgkin Lymphoma ◽  
M1 Macrophages

Reparação óssea no implante dental

2020 ◽  
Vol 12 (45) ◽  
pp. 63-66
Author(s):  
Halim Nagem Filho ◽  
Reinaldo Francisco Maia ◽  
Reinaldo Missaka ◽  
Nasser Hussein Fares
Keyword(s):  
Gene Expression ◽  
Titanium Surface ◽  
Close Contact ◽  
The Other ◽  
Main Function ◽  
Indirect Interaction ◽  
M2 Macrophages ◽  
Activated Macrophages ◽  
M1 Macrophages ◽  
High Production

The osseointegration is the stable and functional union between the bone and a titanium surface. A new bone can be found on the surface of the implant about 1 week after its installation; the bone remodeling begins between 6 and 12 weeks and continues throughout life. After the implant insertion, depending on the energy of the surface, the plasma fluid immediately adheres, in close contact with the surface, promoting the adsorption of proteins and inducing the indirect interaction of the cells with the material. Macrophages are cells found in the tissues and originated from bone marrow monocytes. The M1 macrophages orchestrate the phagocytic phase in the inflammatory region and also produce inflammatory cytokines involved with the chronic inflammation and the cleaning of the wound and damaged tissues from bacteria. On the other hand, alternative-activated macrophages (M2) are activated by IL-10, the immune complex. Its main function consists on regulating negatively the inflammation through the secretion of the immunosuppressant IL-10. The M2 macrophages present involvement with the immunosuppression, besides having a low capacity for presenting antigens and high production of cytokines; these can be further divided into M2a, M2b, and M2c, based on the gene expression profile.

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