• Journal of Radiopharmaceuticals and Molecular Probes
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• v.7 no.1
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• pp.41-49
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• 2021

Diversity and flexibility are two typical hallmarks of macrophages. Two types of macrophages, M1(classically activated macrophages) and M2(alternatively activated macrophages) exist at both ends of the commonly known macrophage polarization. M1 macrophages have inflammatory properties and are primarily responsible for defending against invading bacteria in our body. On the other hand, M2 macrophages are involved in anti-inflammatory responses and tissue remodeling. Polarized migration of macrophages is of increasing interest in regulating the initiation, generation, and resting phases of inflammatory diseases. In this review, it intend to discuss the properties and functions of tumor-associated macrophages based on polarized macrophages that affect inflammatory diseases. In addition, the purpose of this study is to investigate a molecular imaging approach that targets macrophages that affect tumor growth by controlling the polarization of macrophages that affect tumor diagnosis and treatment.

• BMB Reports
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• v.55 no.4
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• pp.166-174
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• 2022

Hepatic macrophages are key immune cells associated with the broad ranges of liver diseases including steatosis, inflammation and fibrosis. Hepatic macrophages interact with other immune cells and orchestrate hepatic immune circumstances. Recently, the heterogenous populations of hepatic macrophages have been discovered termed residential Kupffer cells and monocyte-derived macrophages, and identified their distinct population dynamics during the progression of various liver diseases. Liver injury lead to Kupffer cells activation with induction of inflammatory cytokines and chemokines, which triggers recruitment of inflammatory monocyte-derived macrophages. To understand liver pathology, the functions of different subtypes of liver macrophages should be regarded with different perspectives. In this review, we summarize recent advances in the roles of hepatic macrophages under liver damages and suggest hepatic macrophages as promising therapeutic targets for treating liver diseases.

• Journal of Yeungnam Medical Science
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• v.38 no.4
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• pp.326-336
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• 2021

Background: Sulfation of heparan sulfate proteoglycans (HSPGs) is critical for the binding and signaling of ligands that mediate inflammation. Extracellular 6-O-endosulfatases regulate posttranslational sulfation levels and patterns of HSPGs. In this study, extracellular 6-O-endosulfatases, sulfatase (Sulf)-1 and Sulf-2, were evaluated for their expression and function in inflammatory cells and tissues. Methods: Harvested human peripheral blood mononuclear cells were treated with phytohemagglutinin and lipopolysaccharide, and murine peritoneal macrophages were stimulated with interleukin (IL)-1β for the evaluation of Sulf-1 and Sulf-2 expression. Sulf expression in inflammatory cells was examined in the human rheumatoid arthritis (RA) synovium by immunofluorescence staining. The antigen presentation and phagocytic activities of macrophages were compared according to the expression state of Sulfs. Sulfs-knockdown macrophages and Sulfs-overexpressing macrophages were generated using small interfering RNAs and pcDNA3.1 plasmids for Sulf-1 and Sulf-2, respectively. Results: Lymphocytes and monocytes showed weak Sulf expression, which remained unaffected by IL-1β. However, peritoneal macrophages showed increased expression of Sulfs upon stimulation with IL-1β. In human RA synovium, two-colored double immunofluorescent staining of Sulfs and CD68 revealed active upregulation of Sulfs in macrophages of inflamed tissues, but not in lymphocytes of lymphoid follicles. Macrophages are professional antigen-presenting cells. The antigen presentation and phagocytic activities of macrophages were dependent on the level of Sulf expression, suppressed in Sulfs-knockdown macrophages, and enhanced in Sulfs-overexpressing macrophages. Conclusion: The results demonstrate that upregulation of Sulfs in macrophages occurs in response to inflammation, and Sulfs actively regulate the antigen presentation and phagocytic activities of macrophages as novel immune regulators.

• Molecules and Cells
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• v.44 no.5
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• pp.281-291
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• 2021

Tissue-resident macrophages play an important role in maintaining tissue homeostasis and innate immune defense against invading microbial pathogens. Brain-resident macrophages can be classified into microglia in the brain parenchyma and non-parenchymal brain macrophages, also known as central nervous system-associated or border-associated macrophages, in the brain-circulation interface. Microglia and non-parenchymal brain macrophages, including meningeal, perivascular, and choroid plexus macrophages, are mostly produced during embryonic development, and maintained their population by self-renewal. Microglia have gained much attention for their dual roles in the maintenance of brain homeostasis and the induction of neuroinflammation. In particular, diverse phenotypes of microglia have been increasingly identified under pathological conditions. Single-cell phenotypic analysis revealed that microglia are highly heterogenous and plastic, thus it is difficult to define the status of microglia as M1/M2 or resting/activated state due to complex nature of microglia. Meanwhile, physiological function of non-parenchymal brain macrophages remain to be fully demonstrated. In this review, we have summarized the origin and signatures of brain-resident macrophages and discussed the unique features of microglia, particularly, their phenotypic polarization, diversity of subtypes, and inflammasome responses related to neurodegenerative diseases.

• The Korean Journal of Physiology
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• v.29 no.2
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• pp.251-257
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• 1995

The objective of the present study was to test the effect of platelet-activating factor (PAF) on rat alveolar macrophages. PAF alone did not stimulate superoxide secretion from alveolar macrophages. However, PAF $(10^{-5}\;M)$ significantly enhanced phagocytic activator zymosan-induced superoxide secretion from alveolar macrophages. This enhancement of PAF plus zymosan was 30% above the sum of the separate effects of PAF and zymosan. Similarly, PAF $1.3{\times}(10^{-5}\;M)$ was not a direct stimulant of alveolar macrophages, as it had no stimulatory effect on chemiluminescence generation, but potentiated zymosan-induced activation of chemiluminescence, i.e., 162% above the separate effects of each stimulant. PAF $10^{-16}{\pm}10^{-6}\;M$ also failed to stimulate IL-1 production from alveolar macrophages. In contrast, when both PAF $10^{-10}\;M$ and lipopolysaccharide(LPS) $(1 {\mu}g/ml)$ were added together at the initiation of the culture, IL-1 production was significantly increased indicating the potentiative effects of PAF on IL-1 production by alveolar macrophages. Collectively, these data suggest that PAF alone does not activate the release of bioactive products from alveolar macrophages. However, PAF appears to act as a priming mediator that potentiates stimuli-induced macrophage activity. These novel actions of PAF prove its role as a potent mediator of inflammatory and immune responses in the lung.

• Journal of Acupuncture Research
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• v.34 no.1
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• pp.11-21
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• 2017

Objectives : In this study, we investigated the anti-inflammatory and anti-oxidative effects of MOK, a pharmacopuncture medicine, in lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages. Methods : Peritoneal macrophages were isolated from ICR mice. Primary macrophages were treated with MOK extract (1.25, 2.5, 5, 10, and 20 mg/ml) for 30 min and then stimulated with LPS ($1{\mu}g/ml$) for the indicated times. Cytotoxicity was measured using MTT and LDH assays. Nitric oxide (NO) production in culture supernatants was measured using the Griess assay. The mRNA expression of iNOS, COX-2, proinflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$, and IL-6) and antioxidant enzymes (HO-1 and MnSOD) was measured by RT-PCR. Results : Treatment with MOK extract (2.5, 5, and 10 mg/ml) significantly decreased LPS-induced NO production in peritoneal macrophages through inhibition of iNOS expression. The expression of COX-2, TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 mRNA was also decreased in LPS-stimulated macrophages upon treatment with MOK extract. MOK treatment also increased the expression of HO-1 and MnSOD mRNA in macrophages. Conclusion : These results indicate that MOK exerts anti-inflammatory and antioxidant effects by regulating the transcription levels of inflammatory mediators and antioxidant proteins in activated macrophages.

• Food Science and Biotechnology
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• v.15 no.3
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• pp.347-350
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• 2006

The objective of this study was to investigate the possible effects of oral administration of single cell products (SCP) of apple on activating peritoneal macrophages. Apples were processed either for cold-pressed juice or SCP, which were produced by incubating sliced apples with a protopectinase, Sumyzyme MC. Both cold-pressed juice and SCP of apple were administered to C57BL/6 mice for 10 days to compare their efficacy, along with the control group, in stimulating peritoneal macrophages. The viability of macrophages was significantly increased by up to 161% of that of the control following the administration of apple SCP, whereas the viability of macrophages was increased to a lesser extent of up to 143% in the apple juice (AJ) administered group. Administration of apple SCP also induced a significantly higher production of $H_2O_2$ from macrophages (317% of the control) than that of cold-pressed AJ (210%). Although nitric oxide (NO) production was not increased by the administration of either AJ or SCP, the latter slightly but significantly increased tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$) production from macrophages from 560.4 to 579.8 pg/mL. The results of this study suggest that administering SCP is more efficient than administering AJ to stimulate functions of peritoneal macrophages.

• Journal of Food Hygiene and Safety
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• v.11 no.4
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• pp.235-241
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• 1996

The rhamnan sulfate extracted from green algae seaweed, Monostroma nitidum was characterized as activity in vitro culture assay with macrophages from mice. Rhamnan sulfate indicated that F-4-3 fraction enhanced glucose consumption, as well as the production of nitrogen dioxide and tumor necrosis factor(TNF). F-4-3 fraction was also augmented IL-1 secretion from those macrophages. Effects of the pretreatment of peritoneal macrophages with rhamnan sulfate F-4-3 fraction and several polysaccharides as relative standard on the production of H2O2 induced with unopsonized zymosan A were examined. Pretreatment with polysaccharides inhibited the zymosan A mediated H2O2 production by macrophages. The phorbol myristate acetate (PMA) mediated H2O2 production was not affected by the pretreament. These result suggested that pretreatment of rhamnan sulfate interfered with the interaction of macrophages zymosan A. Rhamnan sulfate inhibited zymosan A mediated production of H**O** by macrophages and F-4-3 Fraction was also activator of macrophages.

• Korean Journal of Veterinary Research
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• v.34 no.4
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• pp.857-866
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• 1994

The present study was undertaken to examine the effects of obioactin, lonomycin A, and MDP on toxoplasmacidal activities in glycogen-induced mouse peritoneal macrophages. The killing effect of obioactin on Toxoplasma multiplication was increased significantly in proportion to its concentrations. $O_2{^-}$ generation in obioactin-treated macrophages was also increased from twofold to threefold when compared with that of untreated control. Similarly, $H_2O_2$ continued to rise in parallel with increase of the concentration of obioactin. Lonomycin A-treated macrophages also exhibited a good effect of dose-response on toxoplasmacidal activities. However, $O_2{^-}$ and $H_2O_2$ were not generated significantly in lonomycin A-treated macrophages. Macrophages treated with muramyl dipeptide (MDP) were not found to inhibit the prolifi:ration of Toxoplasma but showed the enhancement of $O_2{^-}$ and $H_2O_2$, generation. The released lysozyme levels from macrophages into cultured media were decreased tn dose-dependent fashion by in vitro treatment of obioactin, lonomycin A, and MDP. The intracellular lysozyme levels appeared to be a constant value regardless of increasing the concentrations of obioactin, lonomycin A, and MDP. Therefore, these results suggest that Toxoplasma multiplication within macrophages treated with obioactin was inhibited by the generation of $O_2{^-}$ and $H_2O_2$ and that lysozyme per se within or released from macrophages had no effect on toxoplasmacidal activity.

• Parasites, Hosts and Diseases
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• v.32 no.3
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• pp.185-194
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• 1994

The present study was undertaken to assess the role of cytokines in the activation of peritoneal macrophages from Toxoplasma-infected mice. Peritoneal macrophages from Toxoplasma-infected mice (10 cysts of Beverley strain/mouse) were harvested 8 weeks after infection, and incubated with the mitogen-induced lymphokine, recombinant mouse $interferon-{\gamma}(IFN-{\gamma})$, recombinant mouse tumor necrosis $factor-{\alpha}{\;}(TNF-{\alpha})$ alone or in combination with 4$IFN-{\gamma}(IFN-{\gamma}/TNF-{\alpha})$ for 24hr at 37^{\circ}C$, 5% $CO_2$. Macrophage activation was measured by the amount of $H_20_2{\;}and{\;}N0_2^{-}$ production, and antiToxoplasma activities of macrophages. $IFN-{\gamma}{\;}or{\;}IFN-{\gamma}/TNF-{\alpha}-treated$ macrophages from Toxoplasma-infected mice revealed significantly higher $H_20_2$ production than resident macrophages from Toxoplasma-infected mice. The production of $N0_2^{-}{\;}by{\;}TNF-{\alpha}-,{\;}IFN-{\gamma}-{\;}or{\;}IFN-{\gamma}/TNF-{\alpha}-treated$ macrophages from Toxoplasma-infected mice were significantly higher than that by resident macrophages, whereas lymphokine-treated group produced similar amount as that produced by resident macrophages. Anti-Toxoplasma activities of cytokinetreated macrophages from Toxoplasma-infected mice were Significantly higher than those of resident macrophages. $IFN-{\gamma}-treated$ macrophages were significantly increased production of $H_20_2{\;}and{\;}N0_2^{-}$, and anti-Toxoplasma activities of macrophages between normal and Toxoplasma-infected mice, whereas the other cytokine-treated groups were not significant differences between them. These data suggested that IFN-{\gamma}was the only one of cytokines capable of significantly activating the peritoneal macrophages from Toxoplasmainfected mice.