• Journal of Radiopharmaceuticals and Molecular Probes
• /
• v.7 no.1
• /
• pp.41-49
• /
• 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
• /
• v.55 no.4
• /
• pp.166-174
• /
• 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.

• IMMUNE NETWORK
• /
• v.23 no.4
• /
• pp.28.1-28.20
• /
• 2023

Lipid accumulation in macrophages is a prominent phenomenon observed in atherosclerosis. Previously, intimal foamy macrophages (FM) showed decreased inflammatory gene expression compared to intimal non-foamy macrophages (NFM). Since reprogramming of lipid metabolism in macrophages affects immunological functions, lipid profiling of intimal macrophages appears to be important for understanding the phenotypic changes of macrophages in atherosclerotic lesions. While lipidomic analysis has been performed in atherosclerotic aortic tissues and cultured macrophages, direct lipid profiling has not been performed in primary aortic macrophages from atherosclerotic aortas. We utilized nanoflow ultrahigh-performance liquid chromatography-tandem mass spectrometry to provide comprehensive lipid profiles of intimal non-foamy and foamy macrophages and adventitial macrophages from Ldlr^-/- mouse aortas. We also analyzed the gene expression of each macrophage type related to lipid metabolism. FM showed increased levels of fatty acids, cholesterol esters, phosphatidylcholine, lysophosphatidylcholine, phosphatidylinositol, and sphingomyelin. However, phosphatidylethanolamine, phosphatidic acid, and ceramide levels were decreased in FM compared to those in NFM. Interestingly, FM showed decreased triacylglycerol (TG) levels. Expressions of lipolysis-related genes including Pnpla2 and Lpl were markedly increased but expressions of Lpin2 and Dgat1 related to TG synthesis were decreased in FM. Analysis of transcriptome and lipidome data revealed differences in the regulation of each lipid metabolic pathway in aortic macrophages. These comprehensive lipidomic data could clarify the phenotypes of macrophages in the atherosclerotic aorta.

• Journal of Yeungnam Medical Science
• /
• v.38 no.4
• /
• pp.326-336
• /
• 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
• /
• v.44 no.5
• /
• pp.281-291
• /
• 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
• /
• v.29 no.2
• /
• pp.251-257
• /
• 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
• /
• v.34 no.1
• /
• pp.11-21
• /
• 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
• /
• v.15 no.3
• /
• pp.347-350
• /
• 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.

• IMMUNE NETWORK
• /
• v.21 no.2
• /
• pp.13.1-13.19
• /
• 2021

Macrophages are important for the first line of defense against microbial pathogens. Integrin CD11b, which is encoded by Itgam, is expressed on the surface of macrophages and has been implicated in adhesion, migration, and cell-mediated cytotoxicity. However, the functional impact of CD11b on the inflammatory responses of macrophages upon microbial infection remains unclear. Here, we show that CD11b deficiency resulted in increased susceptibility to sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection by enhancing the pro-inflammatory activities of macrophages. Upon infection with MRSA, the mortality of Itgam knockout mice was significantly higher than that of control mice, which is associated with increased production of TNF-α and IL-6. In response to MRSA, both bone marrow-derived macrophages and peritoneal macrophages lacking CD11b produced elevated amounts of pro-inflammatory cytokines and nitric oxide. Moreover, CD11b deficiency upregulated IL-4-induced expression of anti-inflammatory mediators such as IL-10 and arginase-1, and an immunomodulatory function of macrophages to restrain T cell activation. Biochemical and confocal microscopy data revealed that CD11b deficiency augmented the activation of NF-κB signaling and phosphorylation of Akt, which promotes the functional activation of macrophages with pro-inflammatory and immunoregulatory phenotypes, respectively. Overall, our experimental evidence suggests that CD11b is a critical modulator of macrophages in response to microbial infection.

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