scholarly journals Antitumor Macrophage Response to Bacillus pumilus Ribonuclease (Binase)

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Anna Makeeva ◽  
Julian Rodriguez-Montesinos ◽  
Pavel Zelenikhin ◽  
Alexander Nesmelov ◽  
Klaus T. Preissner ◽  
...  
Keyword(s):  
Immune Response ◽  
Bacillus Pumilus ◽  
Adaptor Protein ◽  
Short Exposure ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Macrophage Response ◽  
Pathway Activation ◽  
M1 Phenotype ◽  
Stimulate Tumor Growth

Extracellular bacterial ribonucleases such as binase from Bacillus pumilus possess cytotoxic activity against tumor cells with a potential for clinical application. Moreover, they may induce activation of tumor-derived macrophages either into the M1-phenotype with well-documented functions in the regulation of the antitumor immune response or into M2-macrophages that may stimulate tumor growth, metastasis, and angiogenesis. In this study, binase or endogenous RNase1 (but not RNA or short oligonucleotides) stimulated the expression of activated NF-κB p65 subunit in macrophages. Since no changes in MyD88 and TRIF adaptor protein expression were observed, toll-like receptors may not be involved in RNase-related NF-κB pathway activation. In addition, short exposure (0.5 hr) to binase induced the release of cytokines such as IL-6, МСР-1, or TNF-α (but not IL-4 and IL-10), indicative for the polarization into antitumor M1-macrophages. Thus, we revealed increased expression of activated NF-κB p65 subunit in macrophages upon stimulation by binase and RNase1, but not RNA or short oligonucleotides.

Abstract P318: miR-155 Induces Inflammation by Polarizing M1 Macrophages in a TLR3-induced Preeclamptic Mouse Model

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Valorie L Chiasson ◽  
Kelsey R Bounds ◽  
Derek Charles ◽  
Giuseppina Dusio ◽  
Richard P Tobin ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Mouse Model ◽  
Cardiovascular Effects ◽  
Innate Immune ◽  
Poly I:C ◽  
M2 Macrophages ◽  
Th2 Response ◽  
M1 Macrophages ◽  
Cell Responses ◽  
M1 Phenotype

Placental microRNA (miRNA) expression is known to be dysregulated during preeclampsia (PE), a hypertensive pregnancy disorder but the role it plays in the pathogenesis of PE is currently unknown. We have previously demonstrated that placental miR-155 expression is upregulated (P-PIC: 3.15 fold, p<0.05 vs. controls) in a TLR3-induced PE mouse model similar to PE patients. In addition, poly I:C (PIC) treatment significantly increased systolic blood pressure (SBP) at gestational day 17 in P-PIC WT (147±4.5 mmHg) compared to P WT mice (103±2.7 mmHg), but did not have any effect in P-PIC miR-155 KO mice (101±2 mmHg). In PE there is an increase in the number of total and activated macrophages. M1 macrophages display the capacity to shift T cell responses toward a TH1 while M2 macrophages promote a TH2 response. We hypothesized that TLR3-induced upregulation of miR-155 contributes to hypertension in part by polarizing the macrophages to a M1 phenotype and these effects will be attenuated in P-PIC miR-155 KO mice. Placental flow cytometry analyses demonstrate that administration of poly I:C induced CD45(+) CD11b(+) macrophages in P-PIC WT mice which is attenuated in P-PIC miR-155 KO mice. In addition, placental classical ‘M1’ macrophages CD45(+) CD11b(+) CD86(+) CD206(-) were increased and alternate ‘M2’ macrophages CD45(+) CD11b(+) CD206(+) CD86(-) were decreased in P-PIC WT mice compared to controls. Interestingly, administration of poly I:C did not change M1 macrophages but increased M2 macrophages in P-PIC miR-155 KO mice. P-PIC WT mice exhibited increased placental expression of additional M1 markers (NOS2, IFNg) and decreased expression of M2 markers (Arg1, IL-10) compared to controls by qRTPCR but not in P-PIC miR-155 KO mice. The above observations are also consistent with our splenic flow cytometry and qRTPCR studies. Based on our results, miR-155 activation induces inflammation in part by increasing M1 macrophages thus contributing to hypertension. Targeting the innate immune system by inhibition of monocyte/macrophages may have beneficial cardiovascular effects in women with PE.

scholarly journals The Reactive Oxygen Species in Macrophage Polarization: Reflecting Its Dual Role in Progression and Treatment of Human Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Hor-Yue Tan ◽  
Ning Wang ◽  
Sha Li ◽  
Ming Hong ◽  
Xuanbin Wang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Macrophage Polarization ◽  
Human Diseases ◽  
Environmental Cues ◽  
Oxygen Species ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
M1 Phenotype ◽  
Full Activation ◽  
M1 And M2 Macrophages

High heterogeneity of macrophage is associated with its functions in polarization to different functional phenotypes depending on environmental cues. Macrophages remain in balanced state in healthy subject and thus macrophage polarization may be crucial in determining the tissue fate. The two distinct populations, classically M1 and alternatively M2 activated, representing the opposing ends of the full activation spectrum, have been extensively studied for their associations with several disease progressions. Accumulating evidences have postulated that the redox signalling has implication in macrophage polarization and the key roles of M1 and M2 macrophages in tissue environment have provided the clue for the reasons of ROS abundance in certain phenotype. M1 macrophages majorly clearing the pathogens and ROS may be crucial for the regulation of M1 phenotype, whereas M2 macrophages resolve inflammation which favours oxidative metabolism. Therefore how ROS play its role in maintaining the homeostatic functions of macrophage and in particular macrophage polarization will be reviewed here. We also review the biology of macrophage polarization and the disturbance of M1/M2 balance in human diseases. The potential therapeutic opportunities targeting ROS will also be discussed, hoping to provide insights for development of target-specific delivery system or immunomodulatory antioxidant for the treatment of ROS-related diseases.

scholarly journals Head and neck tumor cells treated with hypofractionated irradiation die via apoptosis and are better taken up by M1-like macrophages

2021 ◽  
Author(s):  
Hanna Wedekind ◽  
Kristina Walz ◽  
Mayte Buchbender ◽  
Thorsten Rieckmann ◽  
Erwin Strasser ◽  
...  
Keyword(s):  
Head And Neck ◽  
Tumor Cells ◽  
M2 Macrophages ◽  
Hematopoietic Growth Factors ◽  
M1 Macrophages ◽  
Macrophage Response ◽  
Gm Csf ◽  
Hpv Status ◽  
The Impact ◽  
Hypofractionated Irradiation

Abstract Purpose The incidence of head and neck squamous cell carcinomas (HNSCC) is increasing worldwide, especially when triggered by the human papilloma virus (HPV). Radiotherapy has immune-modulatory properties, but the role of macrophages present in HNSCC and having contact with irradiated tumor cells remains unclear. The influence of irradiated (2 × 5Gy) HNSCC cells on the (re-)polarization and phagocytosis of human macrophages, either non-polarized or with a more M1 or M2 phenotype, was therefore investigated. Methods Human monocytes were differentiated with the hematopoietic growth factors M‑CSF (m) or GM-CSF (g) and additionally pre-polarized with either interleukin (IL)-4 and IL-10 or interferon (IFN)-γ and lipopolysaccharides (LPS), respectively. Subsequently, they were added to previously irradiated (2 × 5Gy) and mock-treated HPV-positive (UD-SCC-2) and HPV-negative (Cal33) HNSCC cells including their supernatants. Results The HNSCC cells treated with hypofractionated irradiation died via apoptosis and were strongly phagocytosed by M0m and M2 macrophages. M0g and M1 macrophages phagocytosed the tumor cells to a lesser extent. Irradiated HNSCC cells were better phagocytosed by M1 macrophages compared to mock-treated controls. The polarization status of the macrophages was not significantly changed, except for the expression of CD206 on M2 macrophages, which was reduced after phagocytosis of irradiated HPV-negative cells. Further, a significant increase in the uptake of irradiated HPV-positive cells by M0g macrophages when compared to HPV-negative cells was observed. Conclusion HNSCC cells treated with hypofractionated irradiation foster phagocytosis by anti-tumorigenic M1 macrophages. The data provide the first evidence on the impact of the HPV status of HNSCC cells on the modulation of the macrophage response to irradiated tumor cells.

scholarly journals mTORC1-mediated polarization of M1 macrophages and their accumulation in the liver correlate with immunopathology in fatal ehrlichiosis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mohamed Haloul ◽  
Edson R. A. Oliveira ◽  
Muhamuda Kader ◽  
Jakob Z. Wells ◽  
Tyler R. Tominello ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Febrile Illness ◽  
Dependent Manner ◽  
M1 Macrophages ◽  
Macrophage Response ◽  
M1 Phenotype ◽  
Mtorc1 Pathway ◽  
Human Monocytic Ehrlichiosis ◽  
Fatal Sepsis

Abstract A polarized macrophage response into inflammatory (M1) or regenerative/anti-inflammatory (M2) phenotypes is critical in host response to multiple intracellular bacterial infections. Ehrlichia is an obligate Gram-negative intracellular bacterium that causes human monocytic ehrlichiosis (HME): a febrile illness that may progress to fatal sepsis with multi-organ failure. We have shown that liver injury and Ehrlichia-induced sepsis occur due to dysregulated inflammation. Here, we investigated the contribution of macrophages to Ehrlichia-induced sepsis using murine models of mild and fatal ehrlichiosis. Lethally-infected mice showed accumulation of M1 macrophages (iNOS-positive) in the liver. In contrast, non-lethally infected mice showed polarization of M2 macrophages and their accumulation in peritoneum, but not in the liver. Predominance of M1 macrophages in lethally-infected mice was associated with expansion of IL-17-producing T, NK, and NKT cells. Consistent with the in vivo data, infection of bone marrow-derived macrophages (BMM) with lethal Ehrlichia polarized M0 macrophages into M1 phenotype under an mTORC1-dependent manner, while infection with non-lethal Ehrlichia polarized these cells into M2 types. This work highlights that mTORC1-mediated polarization of macrophages towards M1 phenotype may contribute to induction of pathogenic immune responses during fatal ehrlichiosis. Targeting mTORC1 pathway may provide a novel aproach for treatment of HME.

Immunohistochemical Study of M1 and M2 Macrophages Population in Chronic Villitis of the Placenta

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S102-S102
Author(s):  
Erika Egal ◽  
Natalia de Magalhães Rodrigues ◽  
Fernanda Mariano ◽  
Reydson Souza ◽  
Joao Scarini ◽  
...  
Keyword(s):  
Tissue Repair ◽  
Etiologic Agent ◽  
Unknown Etiology ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Effector Cells ◽  
Intervillous Space ◽  
M1 Phenotype ◽  
Chronic Villitis ◽  
M1 And M2 Macrophages

Abstract Introduction Villitis is characterized by the presence of inflammatory infiltrate (CD8 lymphocyte) in the placental villous and is classified as to the etiology in known and unknown. In most cases, villitis is idiopathic (villitis of unknown etiology [VUE]) because no microorganisms are evident and there are no maternal symptoms or signs. It has recently been proposed that pregnancy is, in fact, an active and highly regulated immune process in which macrophages play an important role. Macrophages may present with M1 phenotype, important effector cells, or M2 phenotype, capable of suppressing the function of M1 macrophages and influencing immunoregulation and tissue repair. CD68 antibody recognizes macrophages M1 and M2, whereas CD11c and CD163 antibodies are specific for the identification only of M1 and M2 macrophages, respectively. The objective of our study is to characterize in human placentas in the subpopulation of M1 and M2 macrophages in VUE. Methods Sixteen cases of chronic villitis (all without an identifiable etiologic agent) and three control placentas were examined using immunohistochemistry with antibodies for CD68, CD11c, CD163, and CD3. Results CD68 and CD163 were present in all cases in the normal areas. CD68, CD163, and CD11c were present in the villous stroma and in the intervillous space in the inflamed areas. The percentage of CD68-positive macrophages was higher than CD163- and CD11c-positive macrophages in all specimens studied. A total increase of CD68, CD163, and CD11c with the predominance of CD11c over CD163 in the inflamed areas was observed. Conclusion The predominance of M1 macrophages (CD11c) in the inflamed areas suggests the influence of these cells in the pathogenesis VUE. The higher amount of M2 (CD163) in the inflamed villous compared to normal areas suggests a possible immunoregulatory mechanism of the inflammatory process in VUE.

scholarly journals Dynamics of Polarized Macrophages and Activated CD8+ Cells in Heart Tissue of Atlantic Salmon Infected With Piscine Orthoreovirus-1

2021 ◽  
Vol 12 ◽  
Author(s):  
Muhammad Salman Malik ◽  
Ingvild Berg Nyman ◽  
Øystein Wessel ◽  
Maria K. Dahle ◽  
Espen Rimstad
Keyword(s):  
Skeletal Muscle ◽  
Immune Response ◽  
Atlantic Salmon ◽  
Macrophage Polarization ◽  
Heart Tissue ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Mhc I ◽  
Initial Development ◽  
Cd8 Cells

Piscine orthoreovirus (PRV-1) infection causes heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon (Salmo salar). The virus is also associated with focal melanized changes in white skeletal muscle where PRV-1 infection of macrophages appears to be important. In this study, we studied the macrophage polarization into M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes during experimentally induced HSMI. The immune response in heart with HSMI lesions was characterized by CD8+ and MHC-I expressing cells and not by polarized macrophages. Fluorescent in situ hybridization (FISH) assays revealed localization of PRV-1 in a few M1 macrophages in both heart and skeletal muscle. M2 type macrophages were widely scattered in the heart and were more abundant in heart compared to the skeletal muscle. However, the M2 macrophages did not co-stain for PRV-1. There was a strong cellular immune response to the infection in the heart compared to that of the skeletal muscle, seen as increased MHC-I expression, partly in cells also containing PRV-1 RNA, and a high number of cytotoxic CD8+ granzyme producing cells that targeted PRV-1. In skeletal muscle, MHC-I expressing cells and CD8+ cells were dispersed between myocytes, but these cells did not stain for PRV-1. Gene expression analysis by RT-qPCR complied with the FISH results and confirmed a drop in level of PRV-1 following the cell mediated immune response. Overall, the results indicated that M1 macrophages do not contribute to the initial development of HSMI. However, large numbers of M2 macrophages reside in the heart and may contribute to the subsequent fast recovery following clearance of PRV-1 infection.

scholarly journals Prior Pro-inflammatory Polarization Changes the Macrophage Response to IL-4

2021 ◽  
Author(s):  
Erin M O'Brien ◽  
Kara L Spiller
Keyword(s):  
Tissue Repair ◽  
Chronic Wounds ◽  
Macrophage Polarization ◽  
Phenotypic Switching ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Macrophage Response ◽  
M1 Macrophage ◽  
Gene And Protein Expression ◽  
M2 Phenotype

Tissue repair is largely regulated by diverse macrophage populations whose functions are timing- and context-dependent. The early phase of healing is dominated by pro-inflammatory macrophages, also known as M1, followed by the emergence of a distinct and diverse population that is collectively referred to as M2. The extent of the diversity of the M2 population is unknown. M2 macrophages may originate directly from circulating monocytes or from phenotypic switching of pre-existing M1 macrophages within the site of injury. The differences between these groups have not been investigated, but have major implications for understanding and treating pathologies characterized by deficient M2 activation, such as chronic wounds, which also exhibit diminished M1 macrophage behavior. This study investigated the influence of prior M1 activation on human macrophage polarization to an M2 phenotype in response to IL-4 treatment in vitro. Compared to unactivated (M0) macrophages, M1 macrophages upregulated several receptors that promote the M2 phenotype, including the primary receptor for IL-4. M1 activation also changed the macrophage response to treatment with IL-4, generating an M2-like phenotype with a distinct gene and protein expression signature compared to M2 macrophages prepared directly from M0 macrophages. Functionally, compared to M0-derived M2 macrophages, M1-derived M2 macrophages demonstrated increased migratory response to SDF-1α, and conditioned media from these macrophages promoted increased recruitment of endothelial cells in transwell assays. Together, these findings indicate the importance of prior M1 activation in regulating subsequent M2 behavior, and suggest that augmentation of M1 behavior may be a therapeutic target in dysfunctional tissue repair.

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.

Sign in / Sign up

Export Citation Format

Share Document