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A new era of macrophage-based cell therapy
Na Yi Rang,Kim Sang Wha,Seok Seung Hyeok 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Macrophages are essential innate immune cells found throughout the body that have protective and pathogenic functions in many diseases. When activated, macrophages can mediate the phagocytosis of dangerous cells or materials and participate in effective tissue regeneration by providing growth factors and anti-inflammatory molecules. Ex vivo-generated macrophages have thus been used in clinical trials as cell-based therapies, and based on their intrinsic characteristics, they outperformed stem cells within specific target diseases. In addition to the old methods of generating naïve or M2 primed macrophages, the recently developed chimeric antigen receptor-macrophages revealed the potential of genetically engineered macrophages for cell therapy. Here, we review the current developmental status of macrophage-based cell therapy. The findings of important clinical and preclinical trials are updated, and patent status is investigated. Additionally, we discuss the limitations and future directions of macrophage-based cell therapy, which will help broaden the potential utility and clinical applications of macrophages.
GM-CSF Induces Inflammatory Macrophages by Regulating Glycolysis and Lipid Metabolism
Na, Yi Rang,Gu, Gyo Jung,Jung, Daun,Kim, Young Won,Na, Juri,Woo, Jin Sun,Cho, Joo Youn,Youn, Hyewon,Seok, Seung Hyeok The American Association of Immunologists, Inc. 2016 JOURNAL OF IMMUNOLOGY Vol.197 No.10
<P>GM-CSF induces proinflammatory macrophages, but the underlying mechanisms have not been studied thus far. In this study, we investigated the mechanisms of how GM-CSF induces inflammatory macrophages. First, we observed that GM-CSF increased the extent of LPS-induced acute glycolysis in murine bone marrow-derived macrophages. This directly correlates with an inflammatory phenotype because glycolysis inhibition by 2-deoxyglucose abolished GM-CSF-mediated increase of TNF-alpha,IL-1 beta, IL-6, and IL-12p70 synthesis upon LPS stimulation. Increased glycolytic capacity is due to de novo synthesis of glucose transporter ( GLUT)-1,-3, and-4, as well as c-myc. Mean while, GM-CSF increased 3-hydroxy-3-methyl-glutaryl-CoA reductase, which is the rate-limiting enzyme of the mevalonate pathway. Inhibition of acute glycolysis or 3-hydroxy-3-methyl-glutaryl-CoA reductase abrogated the inflammatory effects of GM-CSF priming in macrophages. Finally, mice with inflamed colons exposed to dextran sodium sulfate containing GLUT-1(high) macrophages led to massive uptake of [F-18]-fluorodeoxyglucose, but GM-CSF neutralization reduced the positron-emission tomography signal in the intestine and also decreased GLUT-1 expression in colonic macrophages. Collectively, our results reveal glycolysis and lipid metabolism created by GM-CSF as the underlying metabolic constructs for the function of inflammatory macrophages.</P>
Comparative proteomics: assessment of biological variability and dataset comparability
Kim, Sa Rang,Nguyen, Tuong Vi,Seo, Na Ri,Jung, Seunghup,An, Hyun Joo,Mills, David A,Kim, Jae Han BioMed Central 2015 BMC bioinformatics Vol.16 No.-
<P><B>Background</B></P><P>Comparative proteomics in bacteria are often hampered by the differential nature of dataset quality and/or inherent biological deviations. Although common practice compensates by reproducing and normalizing datasets from a single sample, the degree of certainty is limited in comparison of multiple dataset. To surmount these limitations, we introduce a two-step assessment criterion using: (1) the relative number of total spectra (<I>R</I><SUB><I>TS</I></SUB>) to determine if two LC-MS/MS datasets are comparable and (2) nine glycolytic enzymes as internal standards for a more accurate calculation of relative amount of proteins. <I>Lactococcus lactis</I> HR279 and JHK24 strains expressing high or low levels (respectively) of green fluorescent protein (GFP) were used for the model system. GFP abundance was determined by spectral counting and direct fluorescence measurements. Statistical analysis determined relative GFP quantity obtained from our approach matched values obtained from fluorescence measurements.</P><P><B>Results</B></P><P><I>L. lactis</I> HR279 and JHK24 demonstrates two datasets with an <I>R</I><SUB><I>TS</I></SUB> value less than 1.4 accurately reflects relative differences in GFP levels between high and low expression strains. Without prior consideration of <I>R</I><SUB><I>TS</I></SUB> and the use of internal standards, the relative increase in GFP calculated by spectral counting method was 3.92 ± 1.14 fold, which is not correlated with the value determined by the direct fluorescence measurement (2.86 ± 0.42 fold) with the <I>p</I> = 0.024. In contrast, 2.88 ± 0.92 fold was obtained by our approach showing a statistically insignificant difference (<I>p</I> = 0.95).</P><P><B>Conclusions</B></P><P>Our two-step assessment demonstrates a useful approach to: (1) validate the comparability of two mass spectrometric datasets and (2) accurately calculate the relative amount of proteins between proteomic datasets.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1186/s12859-015-0561-9) contains supplementary material, which is available to authorized users.</P>
Na, Yi Rang,Hong, Ji Hye,Lee, Min Yong,Jung, Jae Hun,Jung, Daun,Kim, Young Won,Son, Dain,Choi, Murim,Kim, Kwang Pyo,Seok II, Seung Hyeok The American Society for Biochemistry and Molecula 2015 Molecular and Cellular Proteomics Vol.14 No.10
<P>Macrophages are crucial in controlling infectious agents and tissue homeostasis. Macrophages require a wide range of functional capabilities in order to fulfill distinct roles in our body, one being rapid and robust immune responses. To gain insight into macrophage plasticity and the key regulatory protein networks governing their specific functions, we performed quantitative analyses of the proteome and phosphoproteome of murine primary GM-CSF and M-CSF grown bone marrow derived macrophages (GM-BMMs and M-BMMs, respectively) using the latest isobaric tag based tandem mass tag (TMT) labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Strikingly, metabolic processes emerged as a major difference between these macrophages. Specifically, GM-BMMs show significant enrichment of proteins involving glycolysis, the mevalonate pathway, and nitrogen compound biosynthesis. This evidence of enhanced glycolytic capability in GM-BMMs is particularly significant regarding their pro-inflammatory responses, because increased production of cytokines upon LPS stimulation in GM-BMMs depends on their acute glycolytic capacity. In contrast, M-BMMs up-regulate proteins involved in endocytosis, which correlates with a tendency toward homeostatic functions such as scavenging cellular debris. Together, our data describes a proteomic network that underlies the pro-inflammatory actions of GM-BMMs as well as the homeostatic functions of M-BMMs.</P>
Production of Syngas from Oxygen Gasification of Industrial Solid Waste in a Fixed-bed Reactor
( Na-rang Kim ),( Soo-nam Park ),( Jae-hong Min ),( Jae-hoi Gu ),( Sang-ok Choi ),( In-su Lee ),( Soo-tae Choo ) 한국폐기물자원순환학회(구 한국폐기물학회) 2015 한국폐기물자원순환학회 3RINCs초록집 Vol.2015 No.-
Waste gasification technologies are currently proposed as an alternative to conventional Waste-to-Energy plants. Important objective of waste gasification is to convert this solid resource into combustible clean gas at high efficiency. The experiment of the gasification was conducted using a pilot scale waste gasification process. The effect of gasification temperatures on syngas composition, cold gas efficiency and particulate concentration were investigates. The final gasification temperature used ranged from 751~1,188 ℃. The highest CO+H<sub>2</sub> composition of 85.5% and CGE of 67.8% and the lowest particulate concentration of 8,803 mg/Nm<sup>3</sup> were obtained at final gasification temperature of 1,188℃.