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Clinical Oral Investigations May 2021The aim of this study was to investigate the relationship between M1 and M2 macrophage polarization and clinical stage in patients with medication-related osteonecrosis...
OBJECTIVES
The aim of this study was to investigate the relationship between M1 and M2 macrophage polarization and clinical stage in patients with medication-related osteonecrosis of the jaw (MRONJ) who underwent treatment with bisphosphonates or denosumab.
MATERIALS AND METHODS
M1 and M2 macrophage density and expression of interleukin (IL)-6 and IL-10 were assessed on biopsies of mucosal tissues surrounding necrotic bone in 30 MRONJ patients with stages 1-3 and controls. For identification of M1 and M2 macrophages, double CD68/iNOS and CD68/CD206 immunofluorescence staining was conducted, respectively. Computer-assisted immunofluorescence quantification of markers was performed.
RESULTS
Early stage 1 MRONJ patients showed a switch toward the M2 phenotype, as indicated by the higher density of M2 macrophages, the decreased M1/M2 ratio, and the upregulation of IL-10. MRONJ patients with advanced stages 2 and 3 showed a shift toward M1-polarized macrophages, as suggested by the higher density of M1 macrophages, the increased M1/M2 ratio, and the overexpression of IL-6. The macrophage density of both M1 and M2 subsets was significantly enhanced in patients receiving bisphosphonates compared with those receiving denosumab.
CONCLUSIONS
The M1-M2 macrophage polarization status in mucosal tissues bordering necrotic bone correlates with clinical stage of MRONJ. Patients with early-stage MRONJ show a switch toward M2-polarized macrophages, while MRONJ patients with advanced stage demonstrate a shift toward the M1 phenotype.
CLINICAL RELEVANCE
Therapeutic molecules targeting the inflammatory microenvironment via the regulation of either M1 or M2 macrophage polarization may represent a novel strategy for treatment of MRONJ.
Topics: Bisphosphonate-Associated Osteonecrosis of the Jaw; Cell Count; Diphosphonates; Humans; Macrophages
PubMed: 32964311
DOI: 10.1007/s00784-020-03602-z -
Medicine May 2018The tumor microenvironment plays a pivotal role in cancer progression. The purpose of the present study was designed to evaluate the predictive value of peripheral... (Observational Study)
Observational Study
The tumor microenvironment plays a pivotal role in cancer progression. The purpose of the present study was designed to evaluate the predictive value of peripheral absolute monocyte count, tumor-associated macrophage, microvessel density, and to clarify the correlation between them in patients with colon cancer.A series of 216 patients with colon cancer were enrolled in this study. The peripheral absolute monocyte count was obtained from preoperative routine blood test. Tumor-associated macrophage and microvessel density were assessed on tissue microarray by immunohistochemistry.The one, three, five-year overall survival rate for the low absolute monocyte count group was 98.4%, 91.1%, 87.1%, respectively; and for the high absolute monocyte count group was 94.6%, 83.7%, 77.2%, respectively (P = .046). The one, three, five-year progression-free survival rate for the low absolute monocyte count group was 94.4%, 87.1%, 85.5%, respectively; and for the high absolute monocyte count group was 90.2%, 75.0%, 73.9%, respectively (P = .024). Univariate and multivariate analysis showed that there was a strong association between peripheral monocyte count and clinical outcome. The correlation between peripheral absolute monocyte count, tumor-associated macrophage, and microvessel density were not observed.The peripheral absolute monocyte count was an independent prognostic factor for overall survival and progression-free survival in colon cancer. The high absolute monocyte count was significantly associated with poor outcome.
Topics: Adult; Aged; Aged, 80 and over; Colonic Neoplasms; Female; Humans; Immunohistochemistry; Leukocyte Count; Macrophages; Male; Microvessels; Middle Aged; Monocytes; Predictive Value of Tests; Prognosis; Survival Rate; Tissue Array Analysis; Young Adult
PubMed: 29794753
DOI: 10.1097/MD.0000000000010759 -
Journal of Nanobiotechnology Dec 2022Nanotopographical cues of bone implant surface has direct influences on various cell types during the establishment of osseointegration, a prerequisite of implant... (Review)
Review
Nanotopographical cues of bone implant surface has direct influences on various cell types during the establishment of osseointegration, a prerequisite of implant bear-loading. Given the important roles of monocyte/macrophage lineage cells in bone regeneration and remodeling, the regulation of nanotopographies on macrophages and osteoclasts has arisen considerable attentions recently. However, compared to osteoblastic cells, how nanotopographies regulate macrophages and osteoclasts has not been properly summarized. In this review, the roles and interactions of macrophages, osteoclasts and osteoblasts at different stages of bone healing is firstly presented. Then, the diversity and preparation methods of nanotopographies are summarized. Special attentions are paid to the regulation characterizations of nanotopographies on macrophages polarization and osteoclast differentiation, as well as the focal adhesion-cytoskeleton mediated mechanism. Finally, an outlook is indicated of coordinating nanotopographies, macrophages and osteoclasts to achieve better osseointegration. These comprehensive discussions may not only help to guide the optimization of bone implant surface nanostructures, but also provide an enlightenment to the osteoimmune response to external implant.
Topics: Osteoclasts; Osseointegration; Cues; Macrophages; Leukocyte Count
PubMed: 36463225
DOI: 10.1186/s12951-022-01721-1 -
Carcinogenesis Dec 2023Copine 1 (CPNE1), a membrane-binding protein, influences the prognosis of various cancers. According to cBioPortal, CPNE1 amplification is a prevalent genetic mutation...
OBJECTIVE
Copine 1 (CPNE1), a membrane-binding protein, influences the prognosis of various cancers. According to cBioPortal, CPNE1 amplification is a prevalent genetic mutation in ovarian cancer but with unknown oncogenic mechanism.
METHODS
This study analysed the CPNE1 expression in ovarian cancer using online datasets, as validated by immunohistochemistry (IHC), quantitative polymerase chain reaction (qPCR) and western blotting. Concurrently, the prognostic value of CPNE1 was accessed. Cell Counting Kit-8, colony formation, transwells and xenograft experiments were performed to evaluate the functions of CPNE1 during ovarian cancer carcinogenesis. CPNE1 and its related genes were analysed by g:Profiler and Tumour Immune Estimation Resource. Furthermore, human monocytic THP-1 cells were co-cultured with ES2 cells to investigate the effect of CPNE1 on macrophage polarization.
RESULTS
The results of bioinformatic analysis, IHC, qPCR and western blotting indicated a higher CPNE1 in ovarian cancer. CPNE1 overexpression demonstrated an association with a poor prognosis of ovarian cancer. Functionally, CPNE1 overexpression increased ES2 and SKOV3 cell proliferation, invasion and migration in vitro and promoted ovarian tumour xenograft growth in vivo, while CPNE1 knockdown led to opposite effects. Additionally, CPNE1 expression demonstrated an association with immune cell infiltration in ovarian cancer, especially macrophage. CPNE1 promoted protumour M2 macrophage polarization by upregulating cluster of differentiation 163 (CD163), CD206 and interleukin-10.
CONCLUSIONS
Our study revealed that CPNE1 mediated M2 macrophage polarization and provided a therapeutic target for ovarian cancer.
Topics: Humans; Female; Cell Line, Tumor; Macrophage Activation; Ovarian Neoplasms; Macrophages
PubMed: 37747823
DOI: 10.1093/carcin/bgad067 -
International Journal of Molecular... Jul 2022Chronic inflammation is implicated in numerous human pathologies. In particular, low-grade inflammation is currently recognized as an important mechanism of... (Review)
Review
Chronic inflammation is implicated in numerous human pathologies. In particular, low-grade inflammation is currently recognized as an important mechanism of osteoarthritis (OA), at least in some patients. Among the signs of the inflammatory process are elevated macrophage numbers detected in the OA synovium compared to healthy controls. High macrophage counts also correlate with clinical symptoms of the disease. Macrophages are central players in the development of chronic inflammation, pain, cartilage destruction, and bone remodeling. However, macrophages are also involved in tissue repair and remodeling, including cartilage. Therefore, reduction of macrophage content in the joints correlates with deleterious effects in OA models. Macrophage population is heterogeneous and dynamic, with phenotype transitions being induced by a variety of stimuli. In order to effectively use the macrophage inflammatory circuit for treatment of OA, it is important to understand macrophage heterogeneity and interactions with surrounding cells and tissues in the joint. In this review, we discuss functional phenotypes of macrophages and specific targeting approaches relevant for OA treatment development.
Topics: Humans; Inflammation; Macrophages; Osteoarthritis; Phenotype; Synovial Membrane
PubMed: 35955514
DOI: 10.3390/ijms23158381 -
BioFactors (Oxford, England) 2014Macrophages are among the first cellular actors facing the invasion of microorganisms. These cells are able to internalize pathogens and destroy them by means of toxic... (Review)
Review
Macrophages are among the first cellular actors facing the invasion of microorganisms. These cells are able to internalize pathogens and destroy them by means of toxic mediators, many of which are produced enzymatically and have strong oxidizing capacity. Indeed, macrophages count on the NADPH oxidase complex activity, which is triggered during pathogen invasion and leads to the production of superoxide radical inside the phagosome. At the same time, the induction of nitric oxide synthase results in the production of nitric oxide in the cytosol which is able to readily diffuse to the phagocytic vacuole. Superoxide radical and nitric oxide react at diffusion controlled rates with each other inside the phagosome to yield peroxynitrite, a powerful oxidant capable to kill micro-organisms. Peroxynitrite toxicity resides on oxidations and nitrations of biomolecules in the target cell. The central role of peroxynitrite as a key effector molecule in the control of infections has been proven in a wide number of models. However, some microorganisms and virulent strains adapt to survive inside the potentially hostile oxidizing microenvironment of the phagosome by either impeding peroxynitrite formation or rapidly detoxifying it once formed. In this context, the outcome of the infection process is a result of the interplay between the macrophage-derived oxidizing cytotoxins such as peroxynitrite and the antioxidant defense machinery of the invading pathogens.
Topics: Animals; Host-Pathogen Interactions; Humans; Immunity, Innate; Macrophages; Oxidation-Reduction; Peroxynitrous Acid; Phagocytosis; Phagosomes
PubMed: 24281946
DOI: 10.1002/biof.1150 -
Frontiers in Immunology 2019Little is known about immune cell infiltrate type in the kidney allograft of patients with chronic-active antibody-mediated rejection (c-aABMR). In this study,...
Little is known about immune cell infiltrate type in the kidney allograft of patients with chronic-active antibody-mediated rejection (c-aABMR). In this study, multiplex immunofluorescent staining was performed on 20 cases of biopsy-proven c-aABMR. T-cell subsets (CD3, CD8, Foxp3, and granzyme B), macrophages (CD68 and CD163), B cells (CD20), and natural killer cells (CD57) were identified and counted in the glomeruli (cells/glomerulus) and the tubulointerstitial (TI) compartment [cells/high-power field (HPF)]. In the glomerulus, T cells and macrophages were the dominant cell types with a mean of 5.5 CD3 cells/glomerulus and 4 CD68 cells/glomerulus. The majority of T cells was CD8 (62%), and most macrophages were CD68CD163 (68%). The TI compartment showed a mean of 116 CD3 cells/HPF, of which 54% were CD8. Macrophage count was 21.5 cells/HPF with 39% CD68CD163. CD20 cells were sporadically present in glomeruli, whereas B-cell aggregates in the TI compartment were frequently observed. Natural killer cells were rarely identified. Remarkably, increased numbers of CD3FoxP3 cells in the TI compartment were associated with decreased graft survival ( = 0.004). Renal allograft biopsies showing c-aABMR show a predominance of infiltrating CD8 T cells, and increased numbers of interstitial FoxP3 T cells are associated with inferior allograft survival.
Topics: Adult; Antibody-Dependent Cell Cytotoxicity; B-Lymphocytes; Biomarkers; Biopsy; Chronic Disease; Female; Graft Rejection; Graft Survival; Humans; Immunophenotyping; Kidney Function Tests; Kidney Transplantation; Lymphocyte Subsets; Macrophages; Male; Middle Aged; Transplantation, Homologous
PubMed: 32117198
DOI: 10.3389/fimmu.2019.03106 -
Experimental Hematology Apr 2020Erythropoiesis in the bone marrow and spleen depends on intricate interactions between the resident macrophages and erythroblasts. Our study focuses on identifying the...
Erythropoiesis in the bone marrow and spleen depends on intricate interactions between the resident macrophages and erythroblasts. Our study focuses on identifying the role of nuclear factor erythroid 2-related factor 2 (Nrf2) during recovery from stress erythropoiesis. To that end, we induced stress erythropoiesis in Nrf2 and Nrf2-null mice and evaluated macrophage subsets known to support erythropoiesis and erythroid cell populations. Our results confirm macrophage and erythroid hypercellularity after acute blood loss. Importantly, Nrf2 depletion results in a marked numerical reduction of F4/80/CD169/CD11b macrophages, which is more prominent under the induction of stress erythropoiesis. The observed macrophage deficiency is concomitant to a significantly impaired erythroid response to acute stress erythropoiesis in both murine bone marrow and murine spleen. Additionally, peripheral blood reticulocyte count as a response to acute blood loss is delayed in Nrf2-deficient mice compared with age-matched controls (11.0 ± 0.6% vs. 14.8 ± 0.6%, p ≤ 0.001). Interestingly, we observe macrophage hypercellularity in conjunction with erythroid hyperplasia in the bone marrow during stress erythropoiesis in Nrf2 controls, with both impaired in Nrf2 mice. We further confirm the finding of macrophage hypercellularity in another model of erythroid hyperplasia, the transgenic sickle cell mouse, characterized by hemolytic anemia and chronic stress erythropoiesis. Our results revealed the role of Nrf2 in stress erythropoiesis in the bone marrow and that macrophage hypercellularity occurs concurrently with erythroid expansion during stress erythropoiesis. Macrophage hypercellularity is a previously underappreciated feature of stress erythropoiesis in sickle cell disease and recovery from blood loss.
Topics: Animals; Antigens, Differentiation; Bone Marrow Cells; Erythropoiesis; Female; Macrophages; Male; Mice; Mice, Knockout; NF-E2-Related Factor 2; Spleen; Stress, Physiological
PubMed: 32151553
DOI: 10.1016/j.exphem.2020.02.005 -
Biomedicine & Pharmacotherapy =... May 2024Studies have shown that Sacubitril/valsartan (Sac/Val) can reduce myocardial inflammation in myocarditis mice, in addition to its the recommended treatment of heart...
Studies have shown that Sacubitril/valsartan (Sac/Val) can reduce myocardial inflammation in myocarditis mice, in addition to its the recommended treatment of heart failure. However, the underlying mechanisms of Sac/Val in myocarditis remain unclear. C-type natriuretic peptide (CNP), one of the targeting natriuretic peptides of Sac/Val, was recently reported to exert cardio-protective and anti-inflammatory effects in cardiovascular systems. Here, we focused on circulating levels of CNP in patients with acute myocarditis (AMC) and whether Sac/Val modulates inflammation by targeting CNP in experimental autoimmune myocarditis (EAM) mice as well as LPS-induced RAW 264.7 cells and bone marrow derived macrophages (BMDMs) models. Circulating CNP levels were higher in AMC patients compared to healthy controls, and these levels positively correlated with the elevated inflammatory cytokines IL-6 and monocyte count. In EAM mice, Sac/Val alleviated myocardial inflammation while augmenting circulating CNP levels rather than BNP and ANP, accompanied by reduction in intracardial M1 macrophage infiltration and expression of inflammatory cytokines IL-1β, TNF-α, and IL-6. Furthermore, Sac/Val inhibited CNP degradation and directly blunted M1 macrophage polarization in LPS-induced RAW 264.7 cells and BMDMs. Mechanistically, the effects might be mediated by the NPR-C/cAMP/JNK/c-Jun signaling pathway apart from NPR-B/cGMP/NF-κB pathway. In conclusion, Sac/Val exerts a protective effect in myocarditis by increasing CNP concentration and inhibiting M1 macrophages polarization.
Topics: Animals; Mice; Myocarditis; Macrophages; Aminobutyrates; Valsartan; RAW 264.7 Cells; Male; Humans; Biphenyl Compounds; Natriuretic Peptide, C-Type; Drug Combinations; Tetrazoles; Acute Disease; Disease Models, Animal; Female; Cytokines; Mice, Inbred C57BL; Anti-Inflammatory Agents; Cell Polarity
PubMed: 38581923
DOI: 10.1016/j.biopha.2024.116535 -
International Journal of Molecular... Jul 2022Macrophages are present in every tissue in the body and play essential roles in homeostasis and host defense against microorganisms. Some tissue macrophages derive from...
Macrophages are present in every tissue in the body and play essential roles in homeostasis and host defense against microorganisms. Some tissue macrophages derive from the yolk sac/fetal liver that populate tissues for life. Other tissue macrophages derive from monocytes that differentiate in the bone marrow and circulate through tissues via the blood and lymphatics. Circulating monocytes are very plastic and differentiate into macrophages with specialized functions upon entering tissues. Specialized monocyte/macrophage subsets have been difficult to differentiate based on cell surface markers. Here, using a combination of "pan" monocyte/macrophage markers and flow cytometry, we asked whether myeloperoxidase (MPO) could be used as a marker of pro-inflammatory monocyte/macrophage subsets. MPO is of interest because of its potent microbicidal activity. In wild-type SPF housed mice, we found that MPO monocytes/macrophages were present in peripheral blood, spleen, small and large intestines, and mesenteric lymph nodes, but not the central nervous system. Only monocytes/macrophages that expressed cell surface F4/80 and/or Ly6C co-expressed MPO with the highest expression in F4/80Ly6C subsets regardless of tissue. These cumulative data indicate that MPO expression can be used as an additional marker to differentiate between monocyte/macrophage subsets with pro-inflammatory and microbicidal activity in a variety of tissues.
Topics: Animals; Biomarkers; Leukocyte Count; Macrophages; Mice; Monocytes; Peroxidase
PubMed: 35897821
DOI: 10.3390/ijms23158246